Fiscal Year 2003 Annual Report

Allen Spiegel, MD

Chairman

Director, NIDDK

Diabetes Mellitus 

Interagency

Coordinating Committee
Fiscal Year 2003 Annual Report

Diabetes Mellitus 

Interagency

Coordinating Committee
CONTENTS

Diabetes Mellitus 

Interagency 

Coordinating Committee

Introduction

3 Activities of Member Organizations

3 Agency for Healthcare Research and Quality (AHRQ)

5 Center for Scientific Review (CSR)

6 Centers for Disease Control and Prevention (CDC)

10 Centers for Medicare & Medicaid Services (CMS)

11 Department of Health and Human Services (DHHS)

11 Office of Public Health and Science (OPHS)

15 Food and Drug Administration (FDA)

16 Health Resources and Services Administration (HRSA)

29 Indian Health Service (IHS)

37 National Center for Complementary and Alternative Medicine (NCCAM)

38 National Center for Health Statistics (NCHS), CDC

39 National Center for Research Resources (NCRR)

42 National Center on Minority Health and Health Disparities (NCMHD)

44 National Eye Institute (NEI)

46 National Heart, Lung and Blood Institute (NHLBI)

48 National Human Genome Research Institute (NHGRI)

50 National Institute of Allergy and Infectious Diseases (NIAID)

53 National Institute of Biomedical Imaging and Bioengineering (NIBIB)

54 National Institute of Child Health and Human Development (NICHD)

56 National Institute of Dental and Craniofacial Research (NIDCR)

57 National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

67 National Institute of Environmental Health Sciences (NIEHS)

69 National Institute of General Medical Sciences (NIGMS)

71 National Institute of Mental Health (NIMH)
71 National Institute of Neurological Disorders and Stroke (NINDS)

72 National Institute of Nursing Research (NINR)

74 National Institute on Aging (NIA)

75 National Institute on Alcohol Abuse and Alcoholism (NIAAA)

76 National Institute on Deafness and Other Communication Disorders (NIDCD)

77 National Institute on Drug Abuse (NIDA)

78 National Library of Medicine (NLM)

79 Veterans Health Administration (VHA)

83 National Diabetes Education Program

89 Meeting Summaries

91 Diabetes Mellitus Interagency Coordinating Committee Meeting – 

February 25, 2003

129 Diabetes Mellitus Interagency Coordinating Committee Meeting – April 11, 2003

141 Diabetes Mellitus Interagency Coordinating Committee Meeting: Use of Special 

Funds for Type 1 Diabetes Research – April 14, 2003

161 Appendicies

163 Appendix A: National Diabetes Mellitus Research and Education Act, Section 429

165 Appendix B: DMICC FY 2003 Roster

CONTENTS
INTRODUCTION

In accordance with Section 429 of the National Diabetes Mellitus Research and Education Act, the Diabetes

Mellitus Interagency Coordinating Committee (DMICC) prepares an annual summary report of its activities as

well as other Federal research activities in the field of diabetes. It is submitted to the Secretary, Department 

of Health and Human Services (DHHS), and the Director of the National Institutes of Health (NIH). This is the

annual report of the DMICC for Fiscal Year (FY) 2003.

LEGISLATIVE MANDATE

The DMICC was authorized by Public Law 93-354 and established in fall 1974; subsequent legislation modified

some of the charges to the Committee. The legislative authority of the Committee is presented in Appendix A.

The charge to the DMICC is to coordinate the research activities of the NIH and other Federal agencies relating 

to diabetes mellitus and its complications and to contribute to the adequacy and technical soundness of these

activities by providing a forum for communication and exchange of information.

The Committee includes representatives from Federal agencies whose programs are relevant to diabetes mellitus

and its complications. The chairman, designated by the Director, NIH, is the Director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). In FY 2003, the DMICC membership included representatives

of 31 Federal organizations. A roster of Committee members as of the close of the fiscal year is included as

Appendix B.

ACTIVITIES OF THE DMICC

The DMICC facilitates cooperation, communication, and collaboration among agencies that conduct or support

diabetes-related activities. These activities may range from support for biomedical research to direct provision 

of health care services. The DMICC provides both a forum for initiating interactions and a mechanism for 

tracking progress.
ACTIVITIES OF MEMBER ORGANIZATIONS
DMICC ANNUAL REPORT 3 FY 2003

Agency for Healthcare Research and Quality

(AHRQ)

http://www.ahrq.gov

The Agency for Healthcare Research and Quality

continues to be involved in a broad range of activities related to improving the quality of health 

care, reducing its costs, improving patient safety,

decreasing medical errors, and broadening access 

to essential services related to diabetes. These 

activities include the support of research and 

collaborations with others in the public and 

private sectors to improve outcomes for those 

with diabetes and to prevent the condition 

across the population.

Current Activities

Prevention - USPSTF. Through the work of the 

U.S. Preventive Services Task Force (USPSTF),

recommendations for screening for type 2 diabetes

and gestational diabetes were updated and 

released in 2003:

• The USPSTF concluded that the evidence is 

insufficient to recommend for or against 

routinely screening asymptomatic adults for 

type 2 diabetes, impaired glucose tolerance,

or impaired fasting glucose.

• The USPSTF recommends screening for 

type 2 diabetes in adults with hypertension 

or hyperlipidemia.

• The USPSTF concluded that the evidence is 

insufficient to recommend for or against routine

screening for gestational diabetes.

Extramural Research. The Agency continues to fund

and is involved with a large number of studies 

related to diabetes:

• Under a partnership with the Health Resources

and Services Administration, AHRQ funded two

studies to assess the impacts of the Health

Disparities Collaboratives. Hundreds of

Community Health Centers have been involved 

in the diabetes collaboratives, a learning 

process built on the Institute for Healthcare

Improvement’s methods for improving care and

outcomes and the Chronic Illness Model. This 

project started in 2001.

• Under the TRIP II (Translating Research Into

Practice II) and EXCEED (Excellence Centers to

Eliminate Ethnic/Racial Disparities) initiatives,

researchers are examining why disparities exist 

in the care and outcomes of minorities with 

diabetes and what can be done to reduce or eliminate them. Projects include an examination of 

the association between diabetes education programs and quality of care indicators in the Indian

Health Service; implementation of successful managed care models of diabetes care in underserved

populations; a community-based participatory

research study aimed to improve processes of care

for elderly African American diabetics; an evaluation of the impact of point-of-service testing of

hemoglobin A1c on care and outcomes; and the

development and evaluation of a culturally sensitive multimedia education program aimed at

increasing diabetes-related knowledge, selfefficacy, and self-care for African American and

Latino populations. Other ongoing studies include

an assessment of diabetes care in community

health centers, the effects of Navajo interpreters

on diabetes outcomes, the effectiveness of an 

automated telephone disease management system

for English- and Spanish-speaking patients, and

an evaluation of the impact of changes in managed

care policy towards reimbursement for glucose

self-monitoring on utilization and outcomes.

ACTIVITIES OF MEMBER ORGANIZATIONS
DMICC ANNUAL REPORT 4 FY 2003

In FY 2003 the Agency funded five new 

studies involving:

• Computerized interviews to assist secondary 

prevention in diabetes care (2003-2005).

• Evaluation of culturally appropriate primary

health care, with particular attention to 

diabetes (2003-2004).

• Efficiency examination in diabetes care 

(2003-2004).

• Home care outcomes of expanded home health

aide roles with particular attention to diabetes

(2003-2007).

• Collaborative Management of Diabetes in 

Blacks (2003-2006).

Intramural Research. Staff at AHRQ are also 

involved in a number of intramural studies of 

diabetes. Investigators are using data from the

Medical Expenditure Panel Survey (MEPS) to 

develop national estimates for medical visits,

individual expenditures, and sources of payment 

for people with diabetes. Another study is 

identifying factors associated with multiple

hospitalizations of diabetics using Healthcare 

Cost and Utilization Project data.

Dissemination of Evidence. AHRQ continues to work

with individuals and organizations to ensure that

the evidence-base is being employed. The Agency has

maintained an initiative launched last year to

strengthen partnerships with stakeholders across

the health care spectrum. Under a partnership with

the American College of Physicians– American

Society of Internal Medicine, the Agency will be

involved with broad efforts to improve the quality of

care for type 2 diabetes. The Agency also continues

its involvement with the National Diabetes Quality

Improvement Alliance (formerly called the Diabetes

Quality Improvement Project (DQIP)), an effort to

develop uniform, core measures of diabetes performance that allow benchmarking across organizations

and identify opportunities for improvement among

health plans and providers. Reporting on DQIP

measures is now required of managed care organizations by the Centers for Medicare & Medicaid

Services (CMS) and results 

will be made publicly available.

Collaborative Work With Other Federal Agencies.

AHRQ is a partner of the Centers for Disease Control

and Prevention (CDC) in the National Public Health

Initiative on Diabetes and Women’s Health. AHRQ is

a partner of CDC in the TRIP initiative as it relates

to diabetes.

National Health Care Quality Report (NHQR) &

National Health Care Disparities Report (NHDR).

These reports were mandated by Congress starting

FY 2003 and will be released to the public in

January 2004. The first provides for the first time,

a systematic picture of the quality of health care in

America and highlights areas where improvement is

needed. The National Healthcare Disparities Report

shows where racial and ethnic inequities exist in

health care delivery and what we can do to improve.

In both, diabetes is a key priority area.

Products

• Program Brief: Diabetes Research Highlight.

Released in April 2003.

• NHQR and NHDR – reports to be released in FY

2004.

• The Agency is currently developing a prototype

“Workbook on Diabetes” for State leaders. The

workbook is based on the methodology and findings of NHQR and NHDR. The major goal is to

serve as a source of data and evaluation of performance including comparative rates among

States. State leaders may be able to improve their

performance by knowing where the gaps are and

perhaps being able to follow best practices established by other States. Scheduled for publication

in FY 2004.
DMICC ANNUAL REPORT 5 FY 2003

• Evidence report on Best Practices on Diabetes.

This is a systematic review of the literature 

currently under development by the University of

California at San Francisco (UCSF)–Stanford

University Evidence-Based Practice Center. It is

scheduled for release in FY 2004.

Future Activities

Much of the work mentioned above will continue

during the next fiscal year. It is expected that 

additional work will be funded under the Agency’s

Program Announcements (PAs) and Requests for

Appications (RFAs). Priorities with particular pertinence to diabetes include translating research into

practice, patient-centered care, patient safety and

medical errors, and the relationship between systems factors and quality. In addition, work will 

continue on the evaluation of quality of care in diabetes and the identification of best practices (quality

measures) as we develop on a yearly basis the NHQR

and NHDR reports.

Center for Scientific Review (CSR)

http://www.csr.nih.gov

The Center for Scientific Review is a center within

NIH, where a majority of investigator-initiated applications in diabetes and obesity areas are reviewed.

The mechanisms of application support are the

investigator-initiated individual project applications

(R01s), High Risk/High Impact Pilot grant applications (R21s), Small Business Innovation Research

Applications or Technology Transfer (SBIR/STTR),

and Individual Fellowship Applications: Predoctoral

(F31 and F30), Postdoctoral (F32), and Senior

Fellowships (F33).

Under the above research support application mechanisms, pertinent areas that are covered fall into two

main categories: Basic and Clinical Translational

Research. Areas include: Beta Cell Biology, Islet and

Pancreas Transplantation, Insulin Action, Insulin

Resistance, Pathogenesis of Type 1 and Type 2

Diabetes, and also study of pathogenesis of obesity.

These studies invoke molecular genetic, metabolic

(which includes nutritional interventions), cell,

biological, and histochemical approaches.

These applications are reviewed in several Integrated

Review Groups (IRGs) within which individual 

subcommittees (study sections) are located. Each of

these sub-committees (study sections) has definite

expertise to review specific areas relevant to diabetes

and obesity. Thus, the mission of CSR to activities of

DMICC is central and pivotal through help in maintaining the quality of diabetes and obesity research

in the Nation. The knowledge gained through these

NIH-supported projects would help control/treat type

1 diabetes and type 2 diabetes and obesity in areas

of the world where these diseases are prevalent.
Centers for Disease Control and Prevention (CDC)

http://www.cdc.gov

Mission, Vision and Structure. The mission of the

Centers for Disease Control and Prevention and its

diabetes program is to eliminate the preventable

burden of diabetes through public health actions.

These actions will occur within a vision of “healthier

and safer people.” While the mission and vision of

public health efforts to eliminate the preventable

burden of diabetes are the primary responsibility of

the Division of Diabetes Translation (DDT) at CDC,

several other programs at CDC, including nutrition

and physical activity, laboratory science, cardiovascular disease (CVD), public health genetics, school

programs, and so forth, are essential to the activities

of CDC in diabetes. Further, other U.S. Department of

Health and Human Services agencies, State and local

health departments, private and professional organizations, minority entities, businesses and purchasers

of care, etc., are also essential in the actions of CDC

to address diabetes. While CDC’s DDT is organized

into an Office of Director and two branches—the

Program Development Branch and the Epidemiology

and Statistics Branch—activities within DDT are

divided into those efforts that primarily address

issues of “Knowing, Knowing Why, and Doing.”

Current Activities

Knowing:

1. National Diabetes Surveillance System: CDC 

continues to strengthen and broaden various 

surveillance systems that increasingly provide a

broader and more complete picture of diabetes in

the United States. Efforts to expand the Behavioral

Risk Factor Surveillance System (BRFSS) and its 

diabetes module, a re-designed National Health

Interview Survey (NHIS), additional questions 

with-in the National Health and Nutrition

Examination Survey (NHANES), expansion of the

National Impatient Survey (NIS) system, and augmentation of the Indian Health Service’s Clinical

Surveillance System are examples of a broader and

more complete set of surveillance systems to “know”

the extent and nature of the diabetes burden. Within

these and other systems, new topics (e.g., age of

diagnosis, CVD risk factors, level of amputations)

have been added. Finally, through CDC’s online

Morbidity and Mortality Weekly Report (MMWR)

and other peer-reviewed journals, surveillance information is being more widely and rapidly shared.

2. SEARCH: The SEARCH project, directed by CDC

and importantly co-funded by NIH, is well into its

third year of establishing six registries for diabetes

among youth throughout the United States. A 

uniform population-based registry system is now

well in place, and both prevalence and incidence

cases are being identified and characterized.

Protocols and manuals of operations have been 

finalized, utilized, and now shared nationally and

internationally on CDC’s web site. Initial data indicates that the incidence projections for diabetes in

youth 19 years or less underestimated the frequency

of diabetes, and that it is likely that the number of 

persons with type 1 diabetes mellitus (DM) is likely

to be greater than previously estimated.

3. Forecasting the Burden of Diabetes: Combining

improved surveillance systems with newly developed

computer modeling that can accept a variety of past

trends related to diabetes and the general population and project changes into the future, several

such projections have been accomplished, including

(a) a clear sense of the size of the population burden

of diabetes in 2050 based on cautious interpretation

of data from the past decade (approx. 30 million persons with known DM); and (b) a precise estimate of

the individual risk of developing type 2 diabetes if

born in 2000 (overall, 1 in 3 chances). These projections provide an essential perspective regarding

what the future will look like unless more effective 

preventive and control diabetes programs are put

into action and also the financial and social implications of the present day diabetes epidemic.

DMICC ANNUAL REPORT 6 FY 2003
4. U.S.–Mexico Border Diabetes Project: Given the

increasing power of the global economy as well as

the “internationalization of health and disease,” it 

is important to expand surveillance and program

efforts in cooperation with other countries that

relate to the United States. Efforts over the past 4

years have resulted in population-based data from

the U.S.–Mexican Border regarding prevalence of 

DM and associated risk factors and conditions from

approximately 25,000 persons. Population-based

household surveys have been completed, and data

initially analyzed. The project, being conducted with

four and six U.S. and Mexican states, respectively,

the Mexican Health Ministry, Health Resources and

Services Administration (HRSA), CDC, and others is

now in the process of developing public health programs to improve the prevention and management of

diabetes along the Border.

5. Vision Health in America: A number of vision

abnormalities contribute to substantial loss of 

quality of life and disability among Americans, especially those in the aging population. Diabetes is one

of these important conditions. Yet, there is no population-based surveillance system to both define 

and measure this burden. Under the leadership of

CDC/DDT along with Prevent Blindness America

(PBA), several existing surveillance systems, including the BRFSS and NHANES, are being expanded to

increase information collected from a population

basis regarding both the extent of poor health due

to vision impairment, as well as the etiology of this

vision impairment. These efforts are being coordinated with NIH/National Eye Institute (NEI) and

CDC/National Center for Health Statistics (NCHS).

Knowing Why:

1. TRIAD: The Translating Research Into Action for

Diabetes (TRIAD), a project directed by CDC and

importantly, co-supported by NIH, is systematically

examining structure, process, and outcomes of diabetes care in six large managed care organizations

(MCOs) in the United States. TRIAD by intention

includes a very large percentage of members from

minority communities. Ultimately, quality of care

and those factors that impair the delivery of quality

of care have been identified. Eventually, structured

interventions will be systematically applied in these 

different MCO settings to determine the improvement of delivery of care. Forty investigators are now

involved in TRIAD.

2. Project DIRECT: This community-based diabetes

intervention program, located in an AfricanAmerican component of Raleigh, North Carolina, has

been in place for approximately 8 years. Initially, following an extensive and population-based assessment of the status of diabetes in this community,

interventions—primary, secondary, and tertiary prevention strategies—have been accepted by the community and applied. At present, both longitudinal

and a follow-up cross-sectional assessment is being 

completed. DIRECT is the first comprehensive 

community-based project in the United States to

address the growing burden of diabetes in an

African-American urban city.

3. Health Services Research: This project is 

monitoring the delivery of efficacious preventive

care services in the United States and identifying

barriers to optimal diabetes care, especially at the 

systems level.

4. Primary Prevention of Diabetes–Formative

Research: To inform communications and program

development, CDC/DDT has completed extensive

formative qualitative research to determine individual and community perceptions about primary 

prevention of type 2 diabetes, from within various

communities of culture, businesses and managed 

care, the health care system, and individual health

providers. This rich information has provided convincing data indicating that (a) different views of the

possibilities and benefits of primary prevention exist

among these various populations; and (b) very different strategies need to be developed to engage these

various populations in effective programs to launch

primary prevention programs.

5. Primary Prevention of Diabetes–Identifying

Persons at Risk for Type 2 DM: Through cooperation

with the University of Minnesota, large datasets are

DMICC ANNUAL REPORT 7 FY 2003
being analyzed to establish simple indicators of

individuals likely to develop DM and likely to benefit

from behavioral interventions. Initial study indicates

that “Enlarged Waist and an Elevated Triglyceride”

(EWET) identifies individuals with insulin resistance

and a high risk for subsequent DM.

6. Primary Prevention of Diabetes–Integrated

Chronic Disease Models: Because the development 

of type 2 DM occurs in populations that also are at

high risk for obesity, hypertension, CVD, etc., the

integration at a State-level of models to deliver both

preventive and management strategies needs to be

identified. Five (5) State health departments have

been funded to model different approaches to 

integrating chronic disease prevention, including

type 2 diabetes, in an effort to ultimately combine

coordinated interests in chronic disease control.

Doing:

1. Diabetes Prevention and Control Programs

(DPCPs): CDC/DDT now supports 50 State programs,

the District of Columbia, and 8 territories to apply

public health programs in the management of diabetes mellitus, and since the past year, in efforts to

develop and launch primary prevention strategies

for type 2 DM. At present, 27/50 States have

“Capacity Building” programs, and measurable

progress has now been documented. In addition to

primary prevention, the DPCPs also now include

CVD prevention activities to persons with established DM, and in these efforts, they work very

closely with State-based CVD programs. DPCPs 

continue to be the major venue for delivery of 

all CDC-directed public health programs in the 

United States.

2. Diabetes Collaborative: In cooperation with HRSA

and various Community Health Centers (CHCs),

CDC/DDT and DPCPs (47) are working closely with

the Institute for Healthcare Improvement (IHI) to

implement improved chronic care systems such that

improved management of diabetes would result. The

program has expanded to include now over 600

Community Health Centers, and data indicate (a)

increased ordering of diabetes tests (e.g., A1c); and

(b) improvements in “intermediate outcomes” such as

A1c levels. Further, on a pilot basis at five DPCPs

and CHCs, primary prevention strategies to identify

those at risk for undetected diabetes and prediabetes have been implemented, and by using simple

data sets of existing information, a very high percentage of members of CHCs (i.e., 25%), have been

identified. The expansion of this primary prevention

detections strategy as well as the implementation 

of primary prevention behavior programs is 

presently in place.

3. National Diabetes Education Program (NDEP): In

cooperation with NIH/National Institute of Diabetes

and Digestive and Kidney Diseases (NIDDK), the

NDEP continues to expand, moving now beyond

improved glycemic and CVD regulation, to address

the primary prevention of type 2 diabetes among

those with prediabetes. In addition, improved use 

of Internet-based education programs for health 

systems, health care providers, businesses, and purchasers of care have been put in place. A more efficient and representative administrative structure of

the NDEP, including the Executive, Steering, and

Operations Committees, has been established. The

DPCPs have become more active in the dissemination of NDEP materials and (a) greater attention to

evaluation of the NDEP; (b) expanded interaction

with the American Diabetes Association (ADA) and

American Association of Diabetes Educators (AADE);

and (c) greater emphasis on and attention to materials and programs for minority communities at risk

for diabetes are all being implemented.

4. National Diabetes Prevention Center (NDPC):

Recognizing the remarkable challenge of diabetes

among American Indians, as well as the expanding

efforts by the Indian Health Service (IHS) towards 

diabetes, CDC’s NDPC has been formalized, staffed,

and expanded in effort and partnership. The NDPC,

located in Gallup, New Mexico, now develops materials, programs, and guidance for all Tribal Nations,

usually in concert with each Tribe as well as IHS.

DMICC ANNUAL REPORT 8 FY 2003
5. Business, Managed Care, Purchasers, and Model

Contract Language: CDC/DDT accepts the important

and necessary attention that the business community directs to DM. In this context, and working

with various Schools of Law and Business, several

programs have been developed and implemented

that (a) facilitate the identification of the burden 

of diabetes in a business community; (b) inform 

purchasers of care concerning evidenced-based

approaches to the management or prevention of 

type 2 diabetes; and (c) provide appropriate 

contract language about diabetes that must be

included in State-based Medicaid RFAs (Requests 

for Applications).

6. National Public Health Strategies for Women and

DM: This major new effort, begun approximately 2

years ago, has been further expanded in 2003 with 

two additional conferences to both delineate and

assign important strategies for both the prevention

and management of diabetes among women across

the age-span. Working with its three major cosponsors, ADA, APHA (American Public Health

Association), and ASTHO (Association of State and

Territorial Public Health Officials), CDC has now

developed specific responsibilities for this national

program to add a public health perspective to the

typical clinical program for women with or at risk

for diabetes mellitus.

Future Activities

1. Greater attention will be directed to integrate

diabetes programs with other chronic disease

efforts, such as nutrition and physical activity

strategies; CVD programs; activities among youth,

especially during school; and so forth. Categorical

activities and programs will gradually be imbedded

in larger, more financially supported chronic 

disease initiatives.

2. As programs at CDC in diabetes have grown, along

with improved and expanded surveillance systems

that are being developed, greater and more appropriate accountability efforts will be made.

3. Within the scientific efforts of CDC/DDT, increasing attention to projections of the diabetes burden,

economic analyses, health services research, and 

the application of evidenced-based public health 

strategies will be implemented.

DMICC ANNUAL REPORT 9 FY 2003
Centers for Medicare and Medicaid Services 

(CMS) [formerly HCFA]

http://www.cms.hhs.gov

Diabetes activities at CMS fell into several broad

categories: evaluation of the quality of care provided

to Medicare beneficiaries, national and State-level

quality measurement and improvement projects

designed to improve care for Medicare beneficiaries,

beneficiary educational campaigns, and research to

support quality diabetes care.

Current Activities

The Doctor’s Office Quality Project is a component 

of CMS’ Physician Focused Quality Initiative. The

Physician Focused Quality Initiative builds upon ongoing CMS strategies and programs in other health

care settings in order to: (1) assess the quality of

care for key illnesses and clinical conditions that

affect many people with Medicare, (2) support 

clinicians in providing appropriate treatment of the

conditions identified, (3) prevent health problems

that are avoidable, and (4) investigate the concept 

of payment for performance.

The Physician Focused Quality Initiative includes

the Doctor’s Office Quality (DOQ) Project, the

Doctor’s Office Quality Information Technology

(DOQ–IT) Project, and several Demonstration 

Projects and Evaluation Reports.

• The DOQ Project has two goals. The first goal is to

describe quality of care in the ambulatory setting

in three domains: clinical performance, practice

system assessment survey, and the patient experience of care survey. The second goal is to assess

the feasibility of collecting doctors’ office qualityof-care data.

• The goal for the DOQ–IT Project is to encourage

physician offices to adopt electronic health 

record systems.

• The Demonstration Projects study the impact 

of new payment approaches and new types of

services on beneficiaries, providers, health plans

and States, and the Evaluation Reports validate

the research and demonstration findings.

The Quality Improvement Organizations (QIOs) 

have been working to improve diabetes care in 

the following areas:

• Annual hemoglobin A1c testing.

• Biennial lipid profile.

• Biennial eye examination.

The QIOs are implementing quality improvement

projects in physician offices to improve diabetes care

for the above measures on a statewide basis as well

as working intensively with approximately 5 percent

of the physicians in their State to improve diabetes

care by implementing interventions such as office

system changes, patient care management registries,

and flow sheets or reminder cards. Improving diabetes care will remain a focus as the QIOs move into

their new contract cycle that will begin in 2005.

2003 National QAPI Project–Clinical Health Care

Disparities (CHCD). One option for Medicare + Choice

Organizations (M+COs) undertaking a 2003 QAPI

Project is to focus on Clinical Health Care Disparities. With this project, an M+CO will choose a clinical focus area (of which diabetes is one option) and

will focus interventions on a specific segment of

their enrollee population that experiences disparities in care and treatment of this clinical area. More

information about the QAPI Clinical Health Care

Disparities projects can be found at

www.cms.hhs.gov\healthplans\quality.

Methods for Increasing Communications With People

With Medicare. The Center for Beneficiary Services

has an agreement with the National Diabetes

Educational Program (NDEP) to promote preventive

services for people with Medicare. Currently our

promotion efforts include the “Power To Control

Diabetes Is in Your Hands” brochures, posters,

Community Kits, and Practitioner Kits. We have also

DMICC ANNUAL REPORT 10 FY 2003
DMICC ANNUAL REPORT 11 FY 2003

prepared a new fact sheet that will advise people

with diabetes about the new self-monitoring benefit

and the medical nutrition benefit to supplement the

“Power To Control” campaign. The fact sheet uses 

the existing cleared language from the CMS

Publication #11022, “Medicare Coverage of 

Diabetes Supplies & Services.”

Future Activities

2004 National QAPI Project-Diabetes. Medicare +

Choice organizations undertaking a 2004 QAPI project have the option of conducting either the national

diabetes project as defined by CMS or a regional 

collaborative project of their own choosing. The

national project will allow the M+COs the option of

selecting to focus on reducing disparities in care or

focusing on the larger diabetic population. CMS

encourages strong clinical performance in the care

and treatment of diabetes by offering M+COs the

opportunity to be exempt from this project if they

have reached specific standards of clinical performance. Additional information regarding the 2004

QAPI National Diabetes Project and information

regarding M+COs exempt from the project can be

found at www.cms.hhs.gov\healthplans\quality.

Department of Health and Human Services

(DHHS)

http://www.dhhs.gov

DHHS Office of Public Health and Science (OPHS)

http://www.hhs.gov/agencies/ophs.html

The Office of Public Health and Science (OPHS)

within the Office of the Secretary serves as the focal

point for leadership and coordination in public

health and science across the U.S. Department of

Health and Human Services, provides direction to

program offices within OPHS, and through the

Assistant Secretary for Health provides advice and

counsel on public health and science issues to the

Secretary. OPHS identifies innovative solutions to

public health problems and issues and provides

health policy advice to public health and other 

professionals and information to the public to

improve the prevention and treatment of diseases

including diabetes.

Highlights and future plans of the OPHS program

offices are described below.

Current Activities

Steps to a HealtherUS Initiative: In April 2003,

Secretary Thompson launched his prevention 

initiative, Steps to a HealthierUS, at a summit in

Baltimore, Maryland. Steps to a HealthierUS builds

on the President’s HealthierUS initiative by focusing

on prevention of chronic diseases, such as diabetes,

obesity, asthma, heart disease, stroke, and cancer,

and by encouraging Americans to make healthy food

choices, increase their level of physical activity, and

avoid tobacco use and exposure. A cornerstone of

Steps to a HealthierUS is cooperative agreements,

which were awarded in September 2003 to 12

grantees covering 23 communities. A second prevention summit is planned for April 29–30, 2004. The

Office of Disease Prevention and Health Promotion

within OPHS coordinates the Steps Initiative.
Secretary’s Diabetes Detection Initiative: Finding 

the Undiagnosed: Plans were made for launching a

nationwide initiative aimed at finding the more than

5 million persons with undiagnosed diabetes during

FY 2003. The Office of the Surgeon General was one

of the primary leads in developing this multi-agency

initiative. The initiative’s focus is to help people

understand their risk for diabetes and assist highrisk people in linking the various health care systems for follow-up testing, if needed. The Diabetes

Detection Initiative will be piloted in 10 locations

around the country in FY 2004. The Surgeon General

plans to appear at some of these sites to address the

importance of diabetes prevention, detection, and

appropriate treatment.

The Office of Disease Prevention and Health

Promotion within OPHS serves as the overall coordinator of the national Healthy People 2010 effort.

Diabetes is one of the 28 Healthy People 2010 focus

area chapters. The diabetes focus area identifies 17

specific health promotion and disease prevention

objectives aimed at achieving the goal of using 

prevention programs to reduce the incidence and

economic burden of this disease and to improve the

quality of life for people who have diabetes or who

are at risk for it. A progress review on the diabetes

focus area was held on December 18, 2002, and new

data are added quarterly to the National Center 

for Health Statistics web site DATA 2010. The complete report on the review can be found at 

www.healthypeople.gov/data/2010prog/focus05, and

www.cdc.gov/nchs/about/otheract/hpdata2010/fa5/

diabetes.htm, a web page prepared by the National

Center for Health Statistics that includes additional

information about the review.

The Office of Minority Health (OMH) within OPHS

seeks to improve the health of racial and ethnic

minority populations through the development of

health policies and programs that address health

disparities and gaps. In FY 2003, OMH continued

funding the following three grants and one cooperative agreement that targeted diabetes as a 

priority health issue: 

1. The Bilingual/Bicultural Service Demonstration

Grant Program funds 10 projects that target 

diabetes by utilizing promotores (lay health educators) to conduct education and outreach to the target population; by providing diabetes screening in

community settings such as churches, schools, and

work sites; by fostering case management to assist

individuals with diabetes; by conducting workshops that encourage physical fitness and better

nutrition; and by developing bilingual health education materials. The projects also reach health

care providers to enhance the quality of care

delivered to minorities with limited-English-proficiency (LEP) through cultural competency training

and providing health care facilities with interpreters for LEP patients. During FY 2003, four

projects were in their second year of operation,

and six were in their third and final year.

2. The Health Disparities in Minority Health Grant

Program is intended to demonstrate the merit 

of using local, small-scale programs to address

health problems and issues that affect the health

and well-being of local minority populations.

Several of the projects within this program

addressed diabetes prevention education, selfmanagement education, and access to health 

care for defined minority populations.

3. The Community Programs To Improve Minority

Health Grant Program fosters the use of a community coalition approach to health promotion 

and risk reduction as a means of reaching targeted

minority populations. Project activities seek to

improve the delivery of comprehensive diabetes

care in the community through a patient-based

care management model, health care provider education, and telemedicine technology. These demonstration programs are funded for 3 years.

4. The American Indian Higher Education

Consortium Cooperative Agreement is a collaborative effort between the Centers for Disease Control

and Prevention (CDC), the Indian Health Service 

Diabetes Program, OMH, and 10 Tribal Colleges 

and Universities.

DMICC ANNUAL REPORT 12 FY 2003
Honoring Our Health: Tribal Colleges and

Communities Working Together to Prevent 

Diabetes seeks to:

• Develop infrastructure for diabetes education 

and community mobilization.

• Establish diabetes-related curricula.

• Connect diabetes prevention to land preservation,

aquaculture, gardens, and bison restoration.

• Develop diet-related curricula.

• Increase education, awareness, and the opportunity to practice good health behaviors.

• Support community health and wellness centers.

• Foster faculty development in diabetes-related

fields.

• Stimulate capacity building for health-related

research.

In November 2001, OPHS, in collaboration with the

Office of the Secretary, initiated a partnership with

the ABC Radio Networks to inform minority communities on ways to achieve better health and close

health gaps with the rest of the U.S. population. In

2003, the National Institutes of Health, the Health

Resources and Services Administration, the Centers

for Medicare & Medicaid Services, and the Agency

for Healthcare Research and Quality joined OPHS 

in sponsoring an extensive series of broadcast 

messages on ABC Radio featuring the Department’s

Closing the Health Gap messages. The campaign’s

initial focus on African-American health was

expanded in FY 2003 to include other racial and 

ethnic minority populations. Specifically, OPHS and

agency partners built an extensive series of web

pages featuring the Department’s Spanish language

health education resources. In addition, five health

fairs were held in FY 2003 that brought information

and screening to 7,500 Hispanic consumers. Finally,

a series of broadcast health messages was initiated

including 60-second vignettes and 1-hour talk shows

with Spanish broadcaster Radio Unica.

Another major component of the campaign, Take 

a Loved One to the Doctor Day encourages all

Americans, especially minorities, to become more

involved in their health care. Now established as 

the third Tuesday in September, Doctor Day took

place on September 16, 2003. It drew more than 450

partners in 50 states, the District of Columbia, and

Puerto Rico, and many of these partners sponsored

local health screenings, fairs, and events at community health centers, including diabetes awareness and management activities. During the month

of September 2003, ABC Radio Network ran 180

recorded PSAs on diabetes, 180 10-second live

announcements on diabetes, and posted web-based

information and links on diabetes. ABC Radio ran

these spots on 240 affiliate stations of the ABC

Urban Advantage Network, magazines, the Associated Press, and Scripps-Howard News Service. As a

result of these campaigns and events, OPHS estimates that more than 33 million people had multiple

exposure to DHHS minority health broadcast messages and more than 40 million people were exposed

to DHHS minority health print messages.

The Office on Women’s Health (OWH) within OPHS

reviews current scientific knowledge to prevent,

reduce, or delay onset, morbidity, and mortality of

diabetes and its complications and serves as a

forum to strengthen partnerships and identify 

collaborative opportunities.

OWH and the Coordinating Committee on Women’s

Health, which includes representatives from across

DHHS agencies and staff offices, collaborated with

the American Diabetes Association to convene a

Women and Diabetes Town Hall at the Cannon House

Office Building on May 20, 2003. Recognizing that

DMICC ANNUAL REPORT 13 FY 2003
more than half of those diagnosed with diabetes are

women, the Town Hall provided a forum for information on diabetes in the lives of women across 

the Nation and across the life span. It highlighted

the National Diabetes Education Program’s “Small

Steps. Big Rewards,” the first national diabetes prevention campaign that was launched on November

20, 2002. This initiative builds on results of clinical 

trials that demonstrated modest lifestyle changes

can have a major impact on preventing the disease.

The Town Hall was broadcasted via satellite around

the country, with 77 sites participating. There were

1,579 user sessions on the Diabetes Town Hall 

web site. The House of Representatives’ Women’s

Caucus and Diabetes Caucus were also partners 

in this effort.

The President’s Council on Physical Fitness and

Sports (PCPFS) stresses the health benefits of regular

physical activity for all Americans, including people

with chronic health conditions such as diabetes.

Each November, PCPFS publishes a web site feature

for the American Diabetes Month: “Physical Activity:

A Key to Diabetes Control and Prevention,” which

includes information on physical activity for people

with diabetes and links to other health web sites 

as well.

Federal Information Resources on Diabetes. The

Office of Public Health and Science established and

coordinates several Federal information resource

centers with toll-free call centers and Internet 

portals that provide comprehensive and reliable

health information about the causes, treatment, and

prevention of diabetes. They include the National

Health Information Center (www.healthfinder.gov

and 800–336–4797), the National Women’s Health

Information Center (www.4woman.gov and

800–994–woman), the Office of Minority Health

Resource Center (www.omhrc.gov and

800–444–6472), www.nutrition.gov,

and www.fitness.gov.

Future Activities

Two key initiatives for FY 2004 will be the launching

and evaluation of the Secretary’s Diabetes Detection

Initiative: Finding the Undiagnosed and the FY 2004

Steps to a HealthierUS Summit.

In FY 2004, the Office of Minority Health will solicit

applications for its three grant programs—

1) Bilingual/Bicultural Service Demonstration Grant

Program, 2) Community Programs To Improve

Minority Health Grant Program, and 3) Health

Disparities in Minority Health Grant Program.

DMICC ANNUAL REPORT 14 FY 2003
Food and Drug Administration (FDA)

http://www.fda.gov

Division of Metabolic and Endocrine 

Drug Products

http://www.fda.gov/cder/dmedp

The mission of the Center for Drug Evaluation and

Research of FDA is to facilitate the clinical development and delivery into the marketplace of safe and

effective drugs for human use. The Division of

Metabolic and Endocrine Drug Products works in

collaboration with the pharmaceutical industry and

academia in the area of drugs for the prevention and

treatment of diabetes mellitus and its microvascular

and macrovascular complications.

Current Activities

There are now available in the United States 

multiple insulin products, animal-sourced and

recombinant, the latter category including native

sequence human insulins and insulin analogues

with rapid-acting or long-acting pharmacokinetic

characteristics. At this time, there are no additional

approved hypoglycemic agents for the treatment 

of type 1 diabetes, though the FDA is committed 

to working with sponsors on any and all promising

therapies.

For type 2 diabetes (DM2), in the last near-decade,

FDA has approved drugs in multiple mechanistic

classes. This broadening of the therapeutic armamentarium in DM2 has revolutionized the management of this disease that is epidemic in our society.

There is continued interest in drugs that impact

insulin responsiveness by primary transcriptional 

activation, the so-called PPAR drugs, and FDA is

committed to prudent developmental strategies for

new drugs in this class and others. While many new

drugs show promise in effecting improvements on

glycemic control, the challenge in development and,

with luck, post-approval, is establishing long-term

benefits outweighing risks of monotherapeutic and

combination therapeutic medical regimens, particularly in the cardiovascular system.

With the recognition of diabetes as a “risk equivalent” of coronary artery disease, the assessment of

the effects of potential anti-atherosclerosis therapies on the natural history of the disease in diabetes

and metabolic syndrome is important from the

standpoint of understanding the totality of expected

risks and benefits of these new drugs and, therefore,

in guiding prudent, long-term, preventive therapeutic intervention strategies. The division is engaged 

in ongoing dialogue with industry and thought 

leaders in this area as new data emerge, in hopes 

of establishing scientifically rigorous methods for

determining the cardiovascular benefits, if any, of

primary antidiabetic, anti-obesity, and other riskfactor-modifying drugs.

Health Care Financing Administration (HCFA) 

See Centers for Medicare & Medicaid Services

(CMS)

DMICC ANNUAL REPORT 15 FY 2003
Health Resources and Services Administration

(HRSA)

http://www.hrsa.gov

The Health Resources and Services Administration

manages several health care systems programs that

include diabetes identification, education, prevention, or treatment.

Bureau of Primary Health Care 

HRSA supports the Consolidated Health Center

Program, a health system providing primary and

preventive care to the underserved, which includes

diabetes identification, education, prevention, and

treatment. The health center program is managed 

in HRSA’s Bureau of Primary Health Care (BPHC).

HRSA’s Bureau of Primary Health Care established

two strategic goals: to move toward the elimination

of health disparities and toward a 100 percent

access system for all Americans. The Health Disparities Collaboratives (HDC), started in FY 1999, seeks

to: (1) generate and document improved health outcomes for underserved populations; (2) transform

clinical practice through new evidence based models

of care; (3) develop infrastructure, expertise, and

multi-disciplinary leadership to improve health 

status; and (4) build strategic partnerships.

The HDC program originally focused on diabetes

mellitus—to delay or decrease disease complications

—by implementing an evidence- and populationbased model of care, which relies on knowing which

patients have the illness and helps them participate

in their own care. It has six basic elements: support

of patient self-management, clinical decisions support, delivery system redesign, a clinical information

system, organization of health care, and strong partnerships with local government and community

organizations. Additional clinical areas of focus have

been added to the HDCs, including cardiovascular

disease, asthma, depression, cancer, and prevention.

Current Activities

• 397 health centers participated or are in the initial

learning year of the Health Disparities Collaboratives with a focus on diabetes.

• After completing the year-long collaborative,

health centers continue to receive support—to 

promote the model of care throughout their organizations, bring change to clinics and measure its

impact on the health of underserved patients.

• Orientation and training videos and brochures

describe the program. A distance learning tool was

created to assist with staff turnover at participating health centers. Health centers have integrated

these tools in ongoing staff orientation programs,

increasing sustained organizational changes.

• A software program was developed to meet the

need for a comprehensive prevention and multiple

disease clinical information system.

• The HDCs have brought positive national and

international visibility to Health Centers and the

work to improve health care outcomes in medically underserved and vulnerable populations.

• Depression screening is included in care of 

diabetes patients.

• Partnerships with other Federal agencies, State

diabetes control programs, and private-sector

organizations grow stronger.

Outcomes (through July 2003):

• Health centers continue to report on the shared

key goal that 90 percent of patients with diabetes

will receive two HbA1c tests annually, at least 3

months apart. Starting in 2000, a shared health

outcome measure was added to all the diabetes

collaboratives requiring them to report on control 

DMICC ANNUAL REPORT 16 FY 2003
of glucose levels (average HbA1c), and a selfmanagement support measure. Additional measures focus on prevention of cardiac as well as

microvascular complications, the latter including

eye, kidney, and lower extremity disease.

• There are over 140,000 patient records in health

center chronic disease registries that enable 

centers to track and better manage the delivery 

of health care. Of the patients in registries,

102,260 persons have diabetes and are tracked 

for diabetes care.

• The average HbA1c has decreased from 9.2 

to 8.2 for nearly 24,000 patients in the 

Diabetes 1 Collaborative.

• The average HbA1c has decreased from 8.77 

to 8.06 for more than 32,500 patients in the 

Diabetes 2 Collaborative.

• The average HbA1c has decreased from 8.63 

to 8.03 for more than 8,500 patients in the 

Diabetes 3 Collaborative.

• The average HbA1c has decreased from 8.13 

to 8.05 for more than 5,000 patients in the 

Diabetes 4 Collaborative.

• The aggregate for all 102,000 patients in 

diabetes registries shows the average percentage

of patients with two HbA1c tests in 12 months

increased from 24 percent to 37 percent in all the

Diabetes Collaboratives as they disseminated the

care model throughout the organization and the 

registry size grew to over 102,000. Thirty-nine 

percent or 39,780 patients have documented collaboratively set self-management goals.

Strategic Partnerships and Infrastructure

Development:

• Nine cluster directors and 10 information systems

specialists are employed by the five lead Primary

Care Associations.

• Thirty State-based staff provide additional 

support to the centers.

• Primary Care-Public Health partnerships are 

highlighted as a programmatic success. The partnership with the Centers for Disease Control and

Prevention (CDC) Division of Diabetes Translation

continues to be strengthened.

• 1999: 15 initial partnerships between State

health department Diabetes Control Programs

(DCP) and health centers working on the 

diabetes collaborative.

• 2002: additional 15 partnerships formed

between State health departments Diabetes

Control Programs.

• 2003: 48 partnerships between State health

department Diabetes Prevention and Control

Programs (DPCPs) and Health Centers working

on collaboratives.

Since 2002, the Agency for Health Research and

Quality has assisted with program evaluation 

strategy.

DHHS Diabetes Detection Initiative (DDI)

On behalf of HRSA, BPHC/HRSA is a major participant in the Secretary’s Diabetes Detection Initiative.

The DDI is a U.S. Department of Health and Human

Services (DHHS) interagency activity to identify

Americans with undiagnosed diabetes and to facilitate their participation in management programs

that reduce diabetes complications. The Initiative

centers around a self-assessment tool by which individuals in targeted communities will assess if they

are at high-risk for having diabetes. The tool will

encourage high-risk individuals to seek follow-up

and treatment, if needed, with their primary care

provider, a HRSA-supported health center, an Indian

Health Service facility or Tribal clinic, or another

safety net provider in their community. Starting in 

DMICC ANNUAL REPORT 17 FY 2003
November 2003, the DDI will be piloted in one State

in each of the 10 DHHS regions across the Nation.

Each State will plan a number of community events

to market this program.

BPHC/HRSA has participated in the full range 

of activities related to the development and implementation of the DDI, including participation on the

steering, operations, implementation, evaluation,

and local planning committees. In particular, BPHC

played a critical role in partnering with HRSA-supported State Primary Care Associations to locate and

enlist participation of the HRSA-supported health

centers and other safety-net providers within the

targeted high-risk communities. As of November

2003, 16 HRSA-supported health center grantees

(approximately 29 health center sites) and 14 other

sites (Indian Health Service clinics, the Choctaw

Nation Health Center with 4 satellite sites, hospitals,

and federally qualified health centers) were confirmed implementation sites for the pilot.

Maternal and Child Health Bureau

The Maternal and Child Health Bureau (MCHB)

administers maternal and child health (MCH) Block

Grants to States to support programs that promote

the health of all the Nation’s mothers and children

and ensure statewide systems of health care for the

MCH population. Diabetes screening, education,

prevention, and treatment programs may be supported through these grants.

Additional Title V activities, such as MCH research,

training, genetic services, and MCH improvement

projects, are supported under Special Projects of

Regional and National Significance (SPRANS). While

these activities may not specifically target Diabetes

Mellitus, core elements of community systems of

care serving children with special health care needs

are addressed by the Program for Children with

Special Health Care Needs. The Healthy Start

Initiative to significantly reduce infant mortality 

in targeted communities also includes services

addressing diabetes in mothers and children. In

addition, MCHB promotes diabetes detection and

care through school-based and school-linked health

programs. Finally, the MCH Training Program 

provides training grants to graduate programs and

professional schools to support teaching, research,

and service activities that focus on women and 

children. Its Leadership Education in Adolescent

Health (LEAH), public health nutrition, and pediatric

nutrition grantee programs include diabetes education, and the Indiana LEAH is nationally recognized

for their work in diabetes.

Special Programs Bureau

HRSA’s Special Programs Bureau has been working

with the Organ Procurement and Transplantation

Network, the national system for matching donated

organs with patients on the transplantation waiting

list, to facilitate the allocation of pancreatic organs

for use in pancreatic islet cell transplants in treating

patients with type 1 diabetes mellitus. Approximately 30 investigational new drug (IND) applications are

in effect for the use of islet cell transplants to treat

type 1 diabetes mellitus.

HIV AIDS Bureau

Derangements of glucose metabolism, including both

glucose intolerance and frank diabetes, have been

associated with the use of highly active antiretroviral therapy to treat HIV infection. As part of 

comprehensive primary care, the Ryan White CARE

Act-funded clinical programs provide monitoring,

treatment, patient education, and nutritional counseling for this complication of HIV treatment. The

AIDS Education and Training Centers provide education and training to clinicians regarding this recently described complication and rapidly disseminate

information on new treatment strategies as they

evolve.

DMICC ANNUAL REPORT 18 FY 2003
Office for the Advancement of Telehealth

The Office for the Advancement of Telehealth has 39

active grantees that use telehealth technologies to

provide a range of services to improve the management of diabetic patients. The Office has funded the

Marshfield Medical Foundation to work with the

Office for the Advancement of Telehealth's other

grantees to create technical assistance materials 

for programs that wish to employ telehealth technologies in the management of diabetes.

Bureau of Health Professions

• Division of Medicine and Dentistry

Podogeriatric Cooperative Agreements: Podogeriatric

Cooperative Agreements were signed with Griffin

Hospital in Connecticut, University of Texas at San

Antonio, Memorial Hospital of Rhode Island, and

Ohio State University. In FY 2003, these programs

received funding to develop an interdisciplinary

podogeriatric curriculum and train primary care and

podiatric residents in that curriculum. There was a

focus on the medically underserved geriatric population with chronic conditions, such as diabetes, that

limit their mobility and self-care abilities. These

projects were initiated in FY 2001.

Family Medicine Residency Training Grants:

University of Medicine and Dentistry of New

Jersey–Robert Wood Johnson Medical School: 

This project, initiated in FY 2001, provided for the

development of a Problem Based Learning (PBL) 

curriculum for use in family practice residency education based on 15 health priority areas of Healthy

People 2010, one of which is diabetes.

Brody School of Medicine at East Carolina

University: Diabetes-related objective: increase the

knowledge base, skills, and confidence of family

practice residents in caring for high-risk patients by

using the strategies of care management and group

visits to improve clinical outcomes. At the end of the

curriculum, it is anticipated that the residents will

understand effective strategies for managing chronic

disease and high-risk conditions using care management and group visits. The chronic diseases and

high-risk factors of focus in the curriculum include

diabetes, obesity, and poor nutrition. This project

was initiated in FY 2002.

Riverside County Regional Medical Center: Riverside

County Regional Medical Center Family Practice

Residency Program will develop three innovative,

interdisciplinary curriculum initiatives that will 

better prepare residents for diverse and vulnerable

patient populations. One of these initiatives was to

develop and implement an interdisciplinary diabetes

curriculum focused on uninsured Hispanic population. This project was initiated in FY 2003.

Physician Assistant Training Grant to the University

of Kentucky PA Program: Diabetes-related objective:

revise the Physician Assistant (PA) training program

in order to fully integrate education in prevention of

specific chronic medical conditions and to more

effectively educate practicing providers in preventive

medicine through an annual symposium in preventive medicine. Chronic medical conditions include

obesity, diabetes, and cardiovascular disease. This

project was initiated in FY 2003.

Family Medicine Academic Administrative Units

Grant to the University of Southern California,

Department of Family Medicine: This proposal

sought to expand the research infrastructure and

capabilities of the Department of Family Medicine 

in the Keck School of Medicine at the University 

of Southern California (USC-DFM) by forming a

Practice-Based Research Network (PBRN) in innercity Los Angeles and the surrounding underserved

areas with at least 20 primary care sites. The PBRN

will support research on issues ranging from epidemiological studies of cervical cancer and diabetes

among Los Angeles' most vulnerable populations to

studies of the most effective models for delivering

care to these at-risk populations. The project was

initiated in FY 2002.

DMICC ANNUAL REPORT 19 FY 2003
Family Medicine Pre-doctoral Education Grant to

Brown University School of Medicine, Department 

of Family Medicine: This proposal sought to develop

an innovative, modular family medicine curriculum

focusing on health disparities for the leading causes

of mortality and morbidity and cross-cultural medicine. Using an interdisciplinary project team of 

family physicians, a pediatrician, educational specialists, a medical anthropologist and clinical 

epidemiologists, they are developing, implementing,

refining, evaluating, and disseminating three modules on health disparities in cardiovascular disease,

cancer, and diabetes mellitus. This project was initiated in FY 2001.

Faculty Development in Internal Medicine Grant 

to Dartmouth Medical School: This grant outlined 

a comprehensive community-based Faculty Development Program designed to enhance core teaching

skills in clinical care among predominantly new

community internal medicine preceptors who practice in rural and underserved areas. This planned

approach included four elements, one of which was

to develop a core clinical teaching skills focus on

several different chronic diseases, including diabetes. This project was initiated in FY 2002.

• Division of Nursing

Nurse Education, Practice and Retention: Brazosport

Memorial Hospital has a focus on enhancing diabetes care. They intend to coordinate and provide

diabetes education with all clinical partners, develop

a method to identify new onset diabetics, and obtain

outcome measures of effectiveness of self-care. The

project period is 9/1/03–6/30/06.

Advanced Education Nursing: The University of

South Alabama, College of Nursing prepares

Advanced Gerontological/Diabetes Clinical Managers

to provide health care for underserved and rural

older adults in multiple primary care settings (nursing home, ambulatory care, acute care hospital,

sub-acute/rehabilitation, and long-term care settings). The project period is 7/1/2001–6/30/2004.

• National Health Service Corps 

Workforce Linkage Pilot Project: The majority of this

pilot was carried out in FY 2003 among the National

Health Service Corps (NHSC) Ready Responders

(commissioned officers assigned to underserved

areas and who also receive special training to

respond to regional or national medical emergencies). Each Ready Responder was supplied with

Personal Digital Assistants (PDAs). They use the

PDAs to record health outcome data from those

patients with any of the following conditions: diabetes, hypertension, asthma, obesity, breast cancer,

cervical cancer, and prostate cancer. At least once

per month, the clinicians “sync” their PDAs with a

NHSC accessible server over the Internet (this is

done in compliance with HIPAA standards). The

patient outcome data is then analyzed. Ready

Responders are supplied with evidence-based best

practices and feedback about their patients during

subsequent “sync” processes.

• Division of State Community and Public Health

Quentin N. Burdick Rural Program for Rural Interdisciplinary Training: Quentin N. Burdick project

grantees provide education and training of health

professions students in rural underserved communities and improve access to health care in rural areas.

Projects supported by this grant offer interdisciplinary training, new and innovative teaching methods

for healthcare professionals providing services in a

rural areas, research concerning health care issues

in rural areas, and increased amount of recruitment

and retention of health care practitioners in rural

areas.

The University of Nebraska Medical Center, School

of Allied Health Professions, has a program named

“Team Up for Life in Rural Tribal Communities.”

The primary purpose of this training grant is to 

contribute to the health of rural Native American

communities by training caregivers and diabetic

Tribal members in life-long diabetes self-care management. The training is interdisciplinary and is

directed to health care professions students at an

DMICC ANNUAL REPORT 20 FY 2003
academic health science center, to para-professional

diabetes education assistants at two Tribal colleges,

and to Tribal members with diabetes through Tribal

diabetes centers. This project was funded in FY 2002,

and it will be supported until FY 2005.

The Allied Health Project Grants (AHPG): Allied

health project grantees provide training to allied

health professional students and allied health professionals to become proficient in providing quality

health care for the public. One of topics under the

health promotion and disease prevention is type 1

and type 2 diabetes mellitus. The AHPG implemented

the following three projects concerning type 1 and

type 2 diabetes mellitus:

1. Southeast Alaska Regional Health Consortium in

Alaska is implementing the Community Wellness

Advocate (CWA) training program to train students, especially minority and disadvantaged

enrollees, to provide health promotion and disease

prevention services in underserved areas. One of

the topics covered through this program is type 1

and type 2 diabetes mellitus. In FY 2002, the project produced 14 graduates and program completers. One hundred percent of these graduates

and program completers are minority and disadvantaged students from the rural area in Alaska.

2. Ohio University in Ohio is implementing the

Multidisciplinary Intervention Program for

Diabetic Elderly Population in Appalachia. The

purpose of the project is to meet the multiple

needs of many elderly persons who have diabetes

and live in poor rural communities. In FY 2003,

the project produced 18 graduates and program

completers.

3. College of Menominee Nation in Wisconsin is

implementing the Allied Health Services Focus:

Elderly Native American project. The project trains

allied health and social service personnel in interdisciplinary training that emphasizes geriatric

assessment and rehabilitation on the Menominee

Reservation. One of the topics covered through

this program is type 1 and type 2 diabetes 

mellitus. In FY 2003, the project produced 7 graduates and enrolled 81 students. One hundred 

percent of these graduates and enrollees are

minority and disadvantaged students from the

Menominee Reservation.

All of the above projects were funded in FY 2001 

and they will be supported until FY 2003.

Geriatric Education Centers Program: Geriatric

Education Centers (GECs), collaborative arrangements involving several health professions schools

and health care facilities, facilitate the interdisciplinary training of health professional faculty, students, and practitioners in the diagnosis, treatment,

prevention of disease, disability, and other health

problems of the elderly. Projects supported by these

grants must offer interdisciplinary training involving four or more health professions, one of which

must be allopathic physicians, osteopathic medicine.

In FY 2003, the Geriatric Education Centers Program

has 46 active GEC grants. Each grant is awarded

for up to 5 years. Activities focusing primarily on

diabetes include:

1. The Arkansas Geriatric Education Center at the

University of Arkansas for Medical Sciences developed a video entitled, “Diabetes Management in

Older Adults.” This video addresses the health

issues related to diabetes and recommends strategies to slow down the onset and progression of the

disease. Speakers review population characteristics common in patients with diabetes and discuss

the importance of early screening exams. Strategies are presented to help diabetic patients modify

their lifestyles and improve their quality of life by

integrating a nutritional diet and exercise regimen. Patients and health care providers learn 

first-hand techniques to manage food portions

while preserving the nutritional value of meals.

DMICC ANNUAL REPORT 21 FY 2003
2. The purpose of a project at the Stanford GEC at

Stanford University is to develop, disseminate,

and train faculty, providers and future providers,

and caregivers at all levels in multiple health care 

disciplines to recognize and manage dementia 

and depressions associated with diabetes among 

elders from a number of ethnic and culturally

diverse populations.

3. The Iowa GEC at the University of Iowa has 

developed PowerPoint slides, hour-long video

recordings, and modules on Diabetes Management

in the Elderly from its 2001 Geriatric Grand

Rounds Series.

4. The Geriatric Education Center of Michigan at

Michigan State University developed a one-hour

video lecture on diabetes as part of its Geriatric

Grand Rounds for Rural Health Providers.

5. The South, West & Panhandle Consortium GEC 

of Texas (SWAP–GEC) at the University of Texas

Health Science Center at San Antonio has produced, demonstrated, and replicated a training

program for vision station staff to screen for 

diabetes, counsel clients on disease prevention

behaviors, and detect those behaviors.

6. The Northwest GEC at the University of

Washington developed a self-study module entitled, “Health Promotion for Older Adults: Diabetes

Mellitus.” The module presents information on

type 2 diabetes explaining the physiological mechanisms as well as emphasizing various approaches

to managing the disease. It includes an expanded

section on challenges faced by community

providers, case studies, self-study questions,

resources, and references. The module is available

for free download.

Area Health Education Center (AHEC) Program

Arkansas AHEC held a 2-day program entitled “From

Start to Finish” in March to prepare health professionals to sit for the Certified Diabetes Educator

Exam. The review was hosted on the University of

Arkansas for Medical Sciences campus. Sixteen

Rural Hospital Program sites were also participating

through the interactive television network. Over 235

participants took part, including 80 nurses and 33

dieticians. Thirteen hours of CEU credit were offered

for nurses, pharmacists, and dieticians. The workshop was arranged to provide a broad discussion of

the disease while focusing on specific areas recognized in the exam. The program included physiology

and pathophysiology; acute complications, chronic

complications, management in pregnancy; management in pediatrics; medical nutritional therapy;

exercise and weight management; management 

in geriatrics; reimbursement; American Diabetes

Associantion (ADA) recognition in Arkansas; and

psychosocial concerns.

South Central Texas AHEC center, working with 

12 Texas counties centered on San Antonio/Bexar

County has provided various diabetes-related activities as requested by the communities in the area.

Obesity and diabetes are significant problems in

South Texas, especially among the Hispanic population. (1) In FY 2001–02, they established a “Diabetes

Curriculum” at their web site. The purpose of the

Diabetes Curriculum was to suggest ways in which

area schools might integrate diabetes-related information into their normal coursework. They expect to

maintain and update this information at the web site

as long as it remains useful to their communities.

(2) They have provided videoconferencing equipment

and facilitated health-related programming available

to remote sites in Atascosa, Gillespie, and Guadalupe

Counties. Typically, these programs provide continuing education for health care providers. A number 

of programs have dealt with the prevention and

management of diabetes. (3) For the past few summers, HCOP (Health Career Opportunity Program)

activities have included a one-week Summer Biomedical Camp for high school seniors (30 or so seniors

per year). A stop at the Diabetes Institute in San

Antonio is an important part of the Camp. Other

HCOP activities have included diabetes-related

health fairs and research papers. (4) New in FY

DMICC ANNUAL REPORT 22 FY 2003
2003–04, they are funding a project to provide 

ADA-certified diabetes programs as continuing education to over 500 health care providers annually in

Comal County.

Georgia AHEC's Foothills Center, serving 31 counties

in Northeast Georgia, has co-sponsored for the past

2 years the Athens Diabetes Wellness, a program 

of the American Diabetes Association. In March of

2002, they had 162 participants and in March of

2003, they had 199 participants. This program provides a full day of diabetes education for all people

with type 1 and type 2 diabetes plus family and

friends. They plan to continue their participation in

the program for 2004 in Clarke County, the center of

the service area. On October 4th–November 22, 2003,

they co-sponsored along with Tri-County Health

Systems Community Health Center the Warren,

Greene, Taliaferro, Glascock County “Fit-For-Life

Challenge.” These four counties, located in rural

Northeast Georgia, are all Medically Underserved

Areas. This program provided educational classes 

on Diabetes, Cancer Prevention and Intervention,

Weight Loss and Exercise, Nutrition, and High Blood

Pressure. The Southwest Georgia AHEC Center

reports that they are doing 28 peer to peer (MD) 

2- hour night conferences on standards of care for

diabetics. They are giving a toolkit to each MD who

attends and are offering these programs throughout

a 38-county region. They are only doing rural areas

(no metro areas). Then each MDs provides academic

detailing to his or her office to work with staff on

reminders, jog sheets, and so forth, to help institute

change within the office. It is also to help MDs follow through with complying with the standards.

They give another toolkit to the nurse in the office.

The academic detailing is done by a certified 

diabetes educator (CDE) to ensure quality of information given to staff.

AHEC/HETC Center for southern New Mexico

(SoAHEC) reports two different diabetes projects

going on across five of the six border counties. One

is called LA VIDA (Lifestyles and Values Impacting

Diabetes Awareness) and is funded by the CDC. They

are a contractor in this collaborative through a community health center, Hidalgo Medical Services, Inc.,

and are primarily responsible for the establishment

of diabetes resources centers in the three most

southwestern counties of New Mexico and the 

provision of training and continuing education

opportunities for LA VIDA Coalition staff. They are 

in the third fiscal year of this project and the

resource centers have all been set up, stocked with

culturally appropriate bilingual materials, and computer stations (several per site), and the community

health workers (Promotoras) who run the resource

centers have received a series of ongoing trainings

ranging from accessing diabetes health information

over the Internet to customer service. They are currently coordinating a series of 8 to 10 more trainings

for LA VIDA coalition staff over the next 9 months.

The other project began this past June 2003, and is 

a two-county diabetes prevention initiative (3-year)

funded by a regional foundation, the Paso de Norte

Health Foundation. This initiative is focusing the

first year on bilingual training-of-trainers around

diabetes, nutrition, and physical activity utilizing

various different curricula (both local and national).

The second year they intend to go into the schools

and develop a group of student peer mentors utilizing our already established HCOP students. The

third year, they hope to affect policy and have the

vending machines either removed from the school

premises, or at least offering healthier alternatives.

As part of Year One activities for the latter project,

they will be hosting a "Diabetes Summit" in May

2004 where they intend to bring together as many

programs working in the diabetes arena from both

counties to work on a strategic plan that reduces

duplication of services and strengthens collaboration among providers. They will be contracting with

two external facilitators and using the Future Search

model for this Diabetes Summit.

Southcentral PA Area AHEC has provided several

programs on diabetes: March 5, 2003, a satellite

downlink–Diabetes Issues in the Home and School;

and a “Living Well with Diabetes” program in conjunction with The Milton S. Hershey Medical Center,

Deptartment of Family and Community Medicine,

Hershey, Pennsylvania. This program is an educaDMICC ANNUAL REPORT 23 FY 2003
tional seminar that includes information concerning

healthy lifestyles useful to the diabetic, relatives of

diabetics, and the general population with a desire

for a healthy lifestyle that includes delaying or

avoiding the development of diabetes. A curriculum

booklet is provided to a lay coordinator who has

been prepared for the role by a certified diabetes

educator. The coordinator leads the discussion on

the lifestyle issues and general health living. During

the 2002–2003 time period in question they have 

provided 36 programs with over 500 attendees. They

also co-sponsor a program “Annual Diabetes Update”

with the Cambria-Somerset Council for Education of

Health Care Professionals, Inc., on the campus of the

University of Pittsburgh, Johnstown Campus. This

program, which is a continuing education program

for physicians, nurses, and allied health professionals, was held in April 2003, with 125 attendees. They

plan to hold the above programs for the 2003–2004

fiscal year.

Gulfcoast South AHEC Center in Sarasota, Florida,

provided a continued education program for health

professionals entitled “Diabetes Update” and heavily

promoted in their service area an educational CDROM entitled "Diabetes Mellitus Type Two: Clinical

Practice Guidelines.” Fourteen health professionals

benefited from this self-study and 20 additional

copies were distributed, and an interdisciplinary

group of four students completed 768 hours of 

community service in Manatee County focused on

the impact of diabetes on middle and high school

students predominately from African-American 

and Hispanic backgrounds.

South Carolina (SC) AHEC has had a Diabetes

Initiative the last 5 years. They increase awareness,

offer “Best Practices” for care, and assess the State's

incidence of type 1 and type 2 diabetes through the

annual Diabetes Symposium with 200–250 participants. They offer day-long continuing education programs on diabetes. This past year there were numerous downlinks for programs on this topic as well.

These projects have been operating at about the

same funding level for the last 3 to 4 years. Many 

of the medical students who go out into the community have used diabetes as the focus for their community projects for the last 4 years. The Medical

University of South Carolina (MUSC) Dean's 

students are required to address diabetes in their

Community-Oriented Primary Care (COPC) projects.

Upstate (SC) AHEC offered 7 diabetes-related continuing education programs to 156 health care professionals in their region. Staff work with local

Diabetes Coalitions to address community issues

and by supporting the Diabetes Fall Fair, an annual

event held as a kick-off to Diabetes Awareness

Month in November. The Fair includes pharmaceutical representatives, diabetes product representatives, and speakers on foot care, importance of 

exercise, and food choices, as well as the spiritual

and psychological implications associated with 

diabetes. More than 200 health care professionals,

patients, and caregivers attended this Fair in

October 2002. Upstate AHEC's diabetes-related activities have remained fairly level for the last several

years and, at present, they anticipate continuing

efforts at approximately the same level in the near

future. However, they expect to remain flexible

enough to rapidly deploy resources to address 

emergent needs.

Illinois AHEC Program (Illinois Health Education

Consortium/AHEC) Bridges to Health project reports

that 955 Limited English Proficient (LEP) Latinos

with diabetes have received health education from

community health workers, 133 health care professionals and students have attended cultural 

competency workshops and/or Spanish language

programs, and 5 health promoters have been trained

to provide diabetes education for LEP diabetic

Latinos at 5 Chicago clinics within the Cook County

Bureau of Health Services system. Data indicate that

health education and individual counseling provided

by health promoters to LEP Latinos with diabetes

has significantly reduced patient “no-show” rate

within the patient group health promoters see,

helped reduce the hemoglobin A1c for patients who

DMICC ANNUAL REPORT 24 FY 2003
have received three or more visits, and increased

self-monitoring of blood glucose levels. Bridges to

Health has improved health care services and utilization for LEP Latino diabetic patients within the

CCH Network Diabetes Program (NDP) service area.

In Year 2, this initiative expanded to include diabetes prevention education and cultural competency

training for providers and students in the Chicago

metropolitan area. The NDP of the Cook County

Bureau (the Bureau) of Health Services provides

services to patients with diabetes, with priority

given to those with poor metabolic control and complications. The program is a multidisciplinary team

approach to the management of diabetes with a

strong educational emphasis for both clients and

health care professionals. The Bureau cares for

approximately 30,000 diabetic patients, 40 percent 

of whom are LEP Latinos (12,000 patients). The NDP

Team includes physicians, nurses, psychologists,

registered dieticians, a pharmacist, and health 

promoters.

Southwest Louisiana Area Health Education Center

(SWLAHEC) received a contract award from the

Louisiana Office of Public Health Diabetes Control

Program to implement a diabetes educational 

training program. The Defeat Diabetes...through

Education Program strives to enhance diabetes

training with senior-level undergraduate nursing,

health education, and health promotion students

from several universities in Louisiana. The Defeat

Diabetes project provides development and 

facilitation of education and training partners,

enhancement of curriculum utilized by health care

professionals and educators, delivery of low literacy

and culturally diverse patient education materials,

and delivery of patient incentives for improved selfmanagement of diabetes. Activities of the program

included screenings, foot exams, diabetes education

with diabetic patients, community assessment for

diabetes resources and statistics, and the development of teaching tools. Graduate school nurse 

practitioner students worked to develop teaching

materials to respond to the high proportion of low

literacy diabetic patients in Louisiana. To date the

program has enhanced the diabetes training of 364

health profession students and provided 2,607

patients with diabetes screening and education.

Southside AHEC (Virginia) region is composed of 13

underserved rural counties with large and financially deprived populations, plus three small cities

where there is an emerging type 2 diabetes trend

reaching down into the early teens. Despite funds

precluding any dramatic inroads being made to

address this progressive emerging national health

care crisis, the local health care facilities do conduct

diabetes clinics. In addition, the Southside AHEC in

collaboration with the Piedmont Health District has

a loosely knit group meeting periodically to try and

develop a regional diabetes program in the Piedmont

Health District. Lack of funding has precluded the

program from progressing beyond review and

assessment. The Southside AHEC in collaboration

with the local Piedmont Health District, Southside

Health District, and the Crater Health District (all

within the Southside AHEC region) intends to apply

for the upcoming Federal STEPS Diabetes, Obesity &

Asthma proposal grant for FY 2005.

Eastern Arizona Area Health Education Center

(EAHEC) has developed the Diabetes Prevention 

and Action Class (DPAC). It is a 25-hour curriculum

designed to increase the likelihood that minority/

disadvantaged students enroll in health career education programs upon graduation from high school.

DPAC was delivered to 58 students in 4 freshmanyear health classes at Globe High School during the

2002–2003 school year. The Arizona AHEC Program

has developed a Diabetes Resource Nurse Education

Program and Service Award Project. These are available to registered nurses who live in a community or

area of need as identified by the regional AHECs. The

registered nurse must have an interest in diabetes as

well as reflect the needed individual community criteria that may apply, such as being bilingual in a

border community. The Arizona AHEC Program

financially supported 13 RNs for the completion of a

DMICC ANNUAL REPORT 25 FY 2003
3-day intensive nationally accredited education program for Diabetes Educators, which was held July

22–24, 2003, in Phoenix, Arizona. This program 

prepared registered nurses to sit for the national

Certified Diabetes Educators Exam. The participants

of the July training are developing a statewide network to address their future educational needs

around diabetes, as well as providing a preventive

resource for alleviating professional isolation in

working as the only Diabetes Resource Nurses in

their communities. The Arizona AHEC Program is

assisting them by providing updates and continuing

education information about diabetes through the

facilitation of an online diabetes education forum.

This Program will be offered again in Spring 2004.

Northern Arizona AHEC provides rotations for nursing and social work students at a BPHC diabetes

Health Disparities Collaborative project at North

Country Community Health Center in Flagstaff. It

supports a wellness program at Hopi Jr./Sr. High

School that provides diabetes prevention on the Hopi

Reservation. It also supports a high school program

at the Hopi Health Care Center called Indigenous

Pride Youth Health Workers, in which high school

students do community health projects on diabetes.

The Southeastern Colorado AHEC (SECAHEC) serves

as a regional coordinating agency (RCA) for the

Colorado Trust Healthy People 2010 Initiative.

SECAHEC coordinates eight Colorado Trust grantees

in the region, all of which are focused on diabetes 

prevention through physical activity and nutrition

changes. SECAHEC was responsible for identifying

this problem to the Colorado Trust resulting in

financial support over a 3-year period from the

Colorado Trust. In 2003, SECAHEC hosted its 2nd

Annual "For the Health of It" conference where the

primary focus was primary and secondary prevention of diabetes, physical activity, and nutrition.

Approximately 200 physicians, nurses, dieticians,

coaches, teachers, and the general public attended.

The 3rd annual conference is scheduled for March 5

and 6, 2004. It too will have a strong emphasis on

diabetes prevention, obesity prevention, and physical activity. SECAHEC has participated and supported the Pueblo Community Diabetes Project that

brings business leaders, health care organizations

and professionals, health insurance providers, and

the general community together to address diabetes.

Outcomes to date include collaborative educational

workshops, outreach to local schools, a communitywide physical activity program called “Pueblo on the

Move,” the development of a community web site,

and participation in corporate educational breakfasts. SECAHEC staff members have provided technical and administrative support, assisted in grant

development, served on work groups, and chaired

the Board of Directors during the past year. SECAHEC partnered with the Colorado Prevention Center

to launch a comprehensive medical prevention and

education program for 25 local physicians who are

participating in the “medical detailing” over the next

year. The effort is a secondary prevention intervention for cardiovascular disease and diabetes. A second prong of the program will train 25 nurses and

pharmacists from the southeast corner of the region

about the latest practice guidelines. Other diabetesrelated activities include participation in the local

school district 

consolidated school health advisory committee

where the major focus for the past year-and-a-half

has been obesity and physical activity in children. A

variety of educational trainings specifically related

to diabetes prevention and care have also been

offered. For example, in October 2003, SECAHEC

hosted a 2-day training for a course that provided a

comprehensive overview of diabetes care, population

health management strategies to increase a participant's competency about diabetes care, discussion

of the latest in diabetes and prevention based on

ADA standards of care, and strategies for collaborative practice and population health management.

Western Colorado AHEC sponsored a 1-day 

western slope Diabetes Extravaganza in September

2003 to address the increasing need for prevention

and treatment-related diabetes education. There was

a minimum of 300 individuals in attendance with

nationally recognized speakers. There were approximately 20 RD and RN professionals in attendance

representing small rural communities. This coming

year Western Colorado AHEC has plans to (1) conDMICC ANNUAL REPORT 26 FY 2003
duct a second day-long diabetes event for consumers

and providers in another part of their 21-county

region in partnership with the Mesa County Health

Department and its Steps to a HealthierUS grant,

and (2) conduct focus groups with consumers and

providers within their Hispanic and increasing

migrant and farm worker community to identify the

most appropriate ways to deliver culturally appropriate education messages regarding diabetes 

prevention and treatment.

Maine and New Hampshire AHEC has been working

with Northeast Healthcare Quality Foundation on a

diabetes education project whereby records in clinics and private offices are extracted and a summary

is prepared. The information is presented back to the

practices in a “Lunch N' Learn” to the entire staff of

the practice in an effort to improve the quality of

care as reflected in real numbers from their own

files. The role of the AHEC has been to identify practices that might be interested and provide logistical

support to the educational presentations. They have

recruited a hospital-based practice association into

this effort because many members are also preceptors for students. Future plans are to expand the

program to include the offices of their rural preceptors. At least one staff member is active on the 

ADEF Advisory Committee of a rural hospital. The

Southern New Hampshire AHEC is an active partner

with the New Hampshire Diabetes Education

Program and has collaborated in offering the

Diabetes Today conference providing continuing 

education to over 350 clinicians and diabetes educators. They have offered a number of diabetes trainings both in the evening and using a “Lunch and

Learn” format. Some of the topics include Diabetes

Medication Update; Diabetes Guidelines: Helping the

Patient; Insulin Teaching; and Managing Diabetes in

Your Practice: Caring for Diverse Communities. They

have plans to continue education on diabetes in the

coming year.

Ke Anueue (Hawaii) AHEC is providing Diabetes 

education through their “Ask-a-Doc” program, which

is video teleconferenced through their rural communities in the State. It is a cooperative effort that

involves their three AHEC offices and the community

learning centers that have partnered with other

rural agencies. They also have a partnership with the

Diabetes Counseling and Education Center in Hilo.

They provide screening and counseling services and

conduct nutrition classes.

Ohio Statewide Area Health Education Centers

(AHEC) program presented a statewide conference

April 24, 2003: “Best Practices and Real Results

Conference: Diabetes and Literacy.” Over 100 nurses,

dieticians, physicians, and health educators from 

a variety of practice settings attended the 1-day 

conference. The conference was co-sponsored by the

Ohio Primary Care Association. Continuing education accreditation was through the Medical College

of Ohio. The conference goal was to bring the latest

clinical diabetes research and demonstrated diabetes management practices together with proven

effective approaches for communicating with the

most vulnerable populations for low literacy. Both 

of the AHEC-sponsored summer career camps for

9th graders use diabetes as the clinical topic since

most childern know someone who has it. In addition,

the Ohio AHEC provides a huge number of CME programs in rural areas including many 1-hour or grand

rounds diabetes programs. In May 2003, they offered

a 1-hour CME program for family physicians on

“Guidelines for Diabetes Management.” In September

2003, the AHEC sponsored a diabetes and hypertension screening event at a shopping mall where 

second-year medical students did the screenings 

as a Service Learning activity.

Missouri AHEC program shares with Kirksville

College of Osteopathic Medicine (KCOM) the services

of a Health Outreach Coordinator who provides community and professional education in 12 counties

surrounding Kirksville on type 1and 2 diabetes. This

registered nurse is a certified diabetes educator and

since has offered Chronic Disease Self-Management

training to communities throughout northeast

Missouri, providing individual counseling and supports an outreach clinic allowing diabetes patients

with complex needs to consult an endocrinologist.

Regional AHEC centers in Missouri also offer periodDMICC ANNUAL REPORT 27 FY 2003
ic continuing education on diabetes. The MidMissouri AHEC in 2002 offered programs for health

care providers on recent advances in type 1 and 

type 2 diabetes. In FY 2003, the East Central

Missouri AHEC (affiliated with the Saint Louis

University AHEC Project) provided a CME program

for area professionals.

New York State AHEC System is a co-investigator in

the IDEATel (Informatics for Diabetes Education 

and Telemedicine) project, a major joint research

project of Columbia University School of Medicine

and Upstate Medical University through a Federal

contract with the Centers for Medicare & Medicaid

Services (CMS) (formerly HCFA). The purpose of the

project is to test whether the use of telemedicine and

enhanced diabetes education delivered directly in

the home to Medicare-eligible diabetics living in

HPSAs (Health Professional Shortage Areas) will

result in reduced morbidity and mortality and lower

costs of care. The Institute for Urban Family Health

serves as the New York Metropolitan Region Office

for the New York State AHEC System. As a result,

students placed at any Institute site have the opportunity to be exposed to the work of two important

Federal initiatives addressing diabetes, including

health promotion, nutrition and fitness interventions, and best practices in diabetes care. As a 330

Center, the Institute has participated in the HRSA

Diabetes Collaborative and is in the process of replicating the collaborative goals through the use of an

electronic medical record system at 12 locations. As

the grantee for the REACH program, the Institute

works with a community coalition of 30 community

and faith-based organizations to address racial 

and ethnic disparities in health outcomes related 

to diabetes and heart disease.

North Carolina Northwest AHEC at Wake Forest

University School of Medicine offers a 1-day 

continuing education certificate program for pharmacists designed to provide a unique educational

opportunity in the area of diabetes care, focusing 

on the interpretation of current national guidelines,

including proper diet/exercise and drug therapy.

This continuing education certificate program has

been offered in both 2002 and 2003 and is cosponsored with the North Carolina Greensboro

AHEC. Once pharmacists are certified, they must

renew their certificate each year. The number of participants ranges from 20–30. The North Carolina

Northwest AHEC at Wake Forest University School 

of Medicine also provides a Diabetes Management

Conference co-sponsored with the Diabetes

Conference Center. This continuing education program has been offered in both 2002 and 2003. The

number of participants ranged from 45–75. Other

North Carolina Northwest AHEC programs in the

time period October 1, 2002–September 30, 2003

include The Fifth Annual Diabetes Management

Conference (Pharmacy); Statewide Diabetes

Conference (Public Health); Diabetes Update for

Nurses (Nursing); and Diabetes Awareness, Training

and Action (DATA) Program (Public Health).

Milwaukee AHEC is working with the State of

Wisconsin Division of Public Health's Diabetes

Prevention and Control Program to expand diabetes

prevention and control in Milwaukee and southeastern Wisconsin by (1) assessing community needs

for diabetes interventions, (2) developing, enhancing

and maintaining partnerships with community 

representatives of Milwaukee and southeastern

Wisconsin's major ethnic groups (African-American,

Hispanic/Latino, American Indian and Asian), and (3)

assisting with cooperative agreements and strategic

planning to enhance identification and elimination

of disparities regarding diabetes. Milwaukee AHEC

has hired a Diabetes Prevention and Control

Community Specialist to work with the Division of

Public Health to coordinate these efforts.

DMICC ANNUAL REPORT 28 FY 2003
Indian Health Service (IHS)

http://www.ihs.gov

Overview of the IHS National Diabetes Program

The mission of the IHS National Diabetes Program

(NDP) is to develop, document, and sustain a public

health effort to prevent and control diabetes in

American Indian and Alaska Native (AI/AN) people.

The agency promotes collaborative strategies for 

the prevention of diabetes and its complications in

the 12 IHS Administrative Service Areas (regions)

through coordination of a network of 19 Model

Diabetes Programs and 12 Area Diabetes Consultants. They in turn provide resource distribution,

program monitoring and evaluation activities, and

technical support to 36 Federal hospitals, 63 Federal

health centers, 44 Federal health stations, 13 Tribal

hospitals, 158 Tribal health centers, 76 Tribal health

stations, 34 urban Indian health centers, and 170

Alaska village clinics at the local level in the delivery of comprehensive health care to over 1.5 million

American Indians and Alaska Natives. The NDP also

continued to develop and operate the Special

Diabetes Program for Indians grant program with

318 grantees in 35 States.

The IHS National Diabetes Program provides: 

• Comprehensive diabetes surveillance (including

total and age-specific prevalence rates of diabetes

and diabetic complications across Indian country)

at the local, regional, and national levels through

collaboration with Centers for Disease Control and

Prevention (CDC) epidemiologists and use of contract epidemiologists and statisticians.

• Research translation through training and technical assistance provided via its extensive network.

• Promotion of quality assurance/improvement

activities in clinical and community programs

through updated Standards of Care for Diabetes,

the annual Diabetes Care & Outcomes Audit, and

the Integrated Diabetes Care and Education

Recognition Program.

• Technical support to IHS/Tribal/Urban (I/T/U) 

sites nationwide through bulletins, updates, and

comprehensive website information.

• Resource information on a full complement of

training opportunities, including specialized

training related to primary outpatient treatment

models of diabetes management.

• Health care provider/consumer education

resources and “best practices” information to 

IHS, Tribal, and urban health programs.

• Development, field-testing, and distribution of

Native American-specific diabetes education

printed and audiovisual materials to IHS and

Tribal health centers. In FY 2003, over 5700 diabetes education materials were sent to over 300

I/T/U programs nationwide.

In addition, the NDP serves as the key IHS contact

and source of information for outside organizations

and agencies working on diabetes and disparities

related to diabetes.

Diabetes was one of the most frequently identified

health problems in IHS Area Tribal consultation

workshops for FY 2003 planning. Type 2 diabetes

disproportionately affects AI/AN adults who are 

over three times more likely to have diabetes than

the general U.S. population. A recent alarming trend

is the increase in prevalence of type 2 diabetes 

in young AI/AN. Over an 11-year period, from

1990–2001, the prevalence of diabetes rose 68 percent in AI/AN adolescents and young adults. Recent

data show that diabetes mortality is 4.3 times higher

in the AI/AN population than in the U.S. population.

There was a 24 percent increase in the American

Indian age-adjusted diabetes-related death rate from

1991–1993 to 2000. There is clear evidence that for

Indian people the health disparity related to diabetes is increasing.

DMICC ANNUAL REPORT 29 FY 2003
Current Activities

Special Diabetes Program for Indians: 1997 Balanced

Budget Act, 2001 Consolidated Appropriations Act,

and P.L. 107-360. The IHS National Diabetes Program

administered Year 6 of the Special Diabetes Program

for Indians (SDPI) the 1997 Balanced Budget Act and

the Consolidated Appropriations Act of 2001. One

hundred million dollars per year have been distributed from these funds through 286 non-competitive

grants administered at 318 sites throughout Indian

country. Over 96 percent of these funds are distributed through grants to Tribes, IHS facilities, and

urban Indian centers while 3.8 percent are withheld

for administration of the grant program. Tribal 

entities are the direct recipients of 81 percent of the

grants, while Federal and urban programs comprise

the remainder. The IHS National Diabetes Program

works closely with the Tribal Leaders Diabetes

Committee (TLDC) to administer this program. The

Request for Applications (RFA) developed by the IHS

NDP this year once again included a Best Practices

approach with 14 strategies identified (see below),

researched and compiled for use by applicants. Sixtyseven percent of the grantees have indicated that

they devote a significant portion of their funding to

primary prevention of diabetes. The IHS NDP sponsored a national diabetes conference in collaboration

with the TLDC in Denver, Colorado, in December

2002. The conference featured successful grant 

programs and results of the Diabetes Prevention

Program study.

Congress stipulated that the SDPI have a strong 

evaluation component. To that end, the IHS NDP

applied CDC’s Framework for Public Health

Evaluation, a mixed methods approach (both qualitative and quantitative methods), to the SDPI, and a

preliminary analysis has been completed. A number

of positive, significant short-term and intermediate

term outcomes have been identified. In addition, the

IHS NDP has improved the accuracy of baseline longterm measures (prevalence and mortality) and established a Diabetes Data Warehouse and “Data Mart”

using RPMS (Resource and Patient Management

System) data to measure accurately the long-term

complications of diabetes. A Final Report to the

Congress summarizing the findings from this evaluation has been prepared and is currently being printed. It will be distributed to Congress in early 2004.

The Special Diabetes Program for Indians grant 

program was reauthorized in December 2002, for 5

years (2004–2008).

IHS Used a Best Practices Approach to Sharing

Lessons Learned From the Special Diabetes Program

for Indians. In 2002, based upon Congressional

direction, the IHS NDP developed a consensus-based

Indian health “best practices” approach. This was

accomplished by convening a Best Practices Workgroup, consisting of experts from IHS, the Tribes,

urban Indian organizations, the IHS Model Diabetes

Programs, and project coordinators from SDPI grant

sites. The Workgroup developed 14 Best Practice

Model approaches for successful diabetes prevention, treatment, and education practices in AI/AN

communities based on findings from the latest diabetes scientific research, outcomes studies, and their

own successful experiences. The Best Practice Models

were used by applicants to identify strengths in diabetes resources and services in their communities,

find gaps in diabetes services or programs, establish

program priorities, find best practice models that

could be applied within their own communities, and

to begin a work plan to develop their own local best

practice models.

To assess use of the consensus-based Best Practice

Models for AI/AN Communities, IHS Area Chief

Medical Officers and Area Diabetes Consultants 

completed assessments of Best Practice Model use

with their review of each grant application. Data

were then compiled by the NDP. In 2003, elements of

the Nutrition and Physical Fitness Best Practice

Model approach were used by 72 percent of grant

programs, the Diabetes Screening Best Practice

Model approach was used by 64 percent of grant 

programs, and the Basic Diabetes Care and Education Best Practice Model approach was used by 63

percent of SDPI grantees.

DMICC ANNUAL REPORT 30 FY 2003
Clinical Standards of Care and the IHS Diabetes Care

and Outcomes Audit. In 2003 the IHS National

Diabetes Program updated the IHS Standards of Care

for Diabetes (originally published in 1986) to reflect

new science and best practices. The Annual IHS Diabetes Care and Outcomes Audit, a voluntary medical

records review of 87 clinical care and public health

practices and outcomes, is designed to measure and

trend use of these standards and outcomes of diabetes care, including blood sugar and blood pressure

control, screening for complications, and preventive

health services.

The standards and audit summary results are distributed to providers IHS-wide through a network of

regional Area Diabetes Consultants and local 

Diabetes Coordinators and are used as quality 

indicators at the local, regional, and national levels 

to identify specific problems and to determine policy

and practice. In FY 2003 we reviewed over 30,000

medical records representing care to over 110,000

patients with diagnosed diabetes at 190 IHS/Tribal

health facilities in the 12 IHS Areas.

This diabetes care surveillance system has been

instrumental in the improvement of diabetes care

practices in many Indian health settings. For example, in a special program in Alaska and in northern

Minnesota from 1989–2002, lower extremity amputation rates were reduced by 60 percent in people

with diabetes who received complete foot screening

and protective footwear. This same system enabled

IHS to measure significant improvements in blood

sugar control nationwide and in blood pressure control in Montana after an intensive intervention.

Screening for Diabetes, Pre-diabetes, and Metabolic

Syndrome. Diabetes has reached epidemic proportions in AI/AN communities. To address this epidemic

and to proactively reduce the burden of this disease,

many Tribal communities have planned or established community-based diabetes screening programs. With the publication of the DPP clinical trial

results and the dissemination of these results to our

communities, hope has been given to AI/AN communities that the epidemic of diabetes can be stopped.

To implement the results of these studies to prevent

diabetes, communities must first find those individuals who are at highest risk. This is accomplished

through widespread screening efforts. In 2002, 86

percent of the Special Diabetes Program for Indians

grant programs reported that general screening for

diabetes and pre-diabetes had increased and was a

major emphasis in their diabetes programs, as 

compared with 14 percent prior to SDPI. Screening

for the risks of diabetes in adults identifies people 

at an earlier stage and allows for intervention. In

2002, the diabetes grant programs reported that they

screened adults (ages 26–54 years) for the following

major risk factors:

• 78% screened for pre-diabetes.

• 91% screened for overweight and obesity.

• 39% screened for acanthosis nigricans.

• 18% screened for offspring of a diabetic pregnancy.

Elders have higher rates of diabetes. In 2002, the 

diabetes grant programs reported that they screened

elders (age 55 years and older) for the following

major risk factors:

• 76% screened for pre-diabetes.

• 88% screened for overweight and obesity.

In order to improve the development and implementation of community-based diabetes screening 

programs, IHS NDP is reviewing a Diabetes Screening

Toolkit prepared by the Western Tribal Diabetes

Project and Portland Area Indian Health Service.

Plans are to disseminate the toolkit widely as it 

provides information on readiness assessment,

preparation, implementation, and follow-up. Other

resources will be included in the NDP revision to

support the scientific basis for screening efforts.

Technical assistance and training regarding screening program development and implementation will

be provided at seven Regional Meetings being

planned for SDPI grantees in the upcoming months.

DMICC ANNUAL REPORT 31 FY 2003
A draft version of clinical guidelines for the care 

of individuals with pre-diabetes and metabolic syndrome has been developed and is being modified by

the NDP and the IHS Area Diabetes Consultants.

This will be a useful tool for improving the quality 

of care to individuals who will be identified in these

screening efforts.

In addition, the NDP is an active partner in the

Secretary’s Diabetes Detection Initiative (DDI). The

U.S. Department of Health and Human Services

(DHHS), under the leadership of Secretary Tommy

Thompson, has developed the “Diabetes Detection

Initiative: Finding the Undiagnosed” to address 

this growing public health challenge of undiagnosed

or unrecognized diabetes. Many DHHS agencies 

have significantly contributed to the planning,

implementation, and evaluation of the DDI, including

the Centers for Disease Control and Prevention,

the Health Resources and Services Administration

(HRSA), the Agency for Healthcare Research and

Quality, the Indian Health Service, Centers for

Medicare & Medicaid Services, the Food and Drug

Administration, and the National Institutes of

Health. The IHS NDP Director has served on the

Steering Committee for this Initiative and NDP staff

serve on the Evaluation Team and the Operations

Team. Two AI communities have participated in the

launch—Wind River of Wyoming and Choctaw Nation

of Oklahoma. Tools developed in the Initiative such

as the health care provider tool will be shared with

the Indian health diabetes network. The purpose of

this tool is to (1) help health care professionals see

the steps in the screening/diagnosis process and (2)

give them information on use of the finger-stick blood 

glucose test (capillary test) done in a health care 

setting as part of the algorithm for determining the

need for further testing.

IHS Became a Deeming Entity for Diabetes

Education Certification. In 2003 the IHS National

Diabetes Program, with agency and Tribal leader

support, established an Indian Health Diabetes

Education Accreditation Program and received notification from the Centers for Medicare & Medicaid

Services that the IHS NDP application to become a

deeming entity had been approved (Federal Register,

April 2002). This process allows Indian health 

diabetes education programs to become certified 

and thus seek Medicare reimbursement for diabetes

education. Thus far 12 programs have applied for 

and have become certified (4 new programs in 2003),

2 sites have provisional accreditation, and 1 additional new application is under review.

Obesity Prevention. For 4 years the IHS National

Diabetes Program has coordinated an obesity 

prevention initiative targeting Head Start children

(0–5 years), families, Head Start staff, and AI 

communities. Four Tribal Head Start pilot sites, in

collaboration with their respective community health

partners, have developed obesity and diabetes prevention interventions in their local communities.

Each Head Start site community action plan includes

multifaceted program activities and milestones

focusing on healthy eating, physical activity, healthy

behavior, and community partnerships. The core

component of the initiative is to develop and sustain

local community partnerships in the implementation

of each program’s interventions.

The Initiative is presently involved in dissemination

activities and sharing promising practices with 

other Head Start programs. In 2003 the Initiative

expanded to include breastfeeding promotion for

Early Head Start grantees. The first focus group was

conducted and recommendations for future 

directions were finalized.

Medical Nutrition Therapy (MNT) and Diabetes 

Self-Management Training (DSMT) for Medicare

Beneficiaries. IHS NDP is taking an active role in the

rapid dissemination of information on the two new

Medicare Part B Benefits: Medical Nutrition Therapy

(MNT) and Diabetes Self-Management Training

(DSMT) for Medicare Beneficiaries who have diabetes

and/or kidney disease. We provide technical assistance and consultation to the I/T/U clinicians and

medical records and patient billing office staff on

putting systems into place for electronic billing,

medical records documentation (i.e., MNT PCC+),

tracking of claims and reimbursements, and impleDMICC ANNUAL REPORT 32 FY 2003
menting systems to determine outcome and costeffectiveness of these services. This provided another

opportunity to promote and facilitate the implementation of the new third-party collections opportunities within the I/T/U system.

Joslin Vision Network Teleophthalmology Project. In

FY 2002 Congress increased the IHS appropriation to

address evaluating American Indians and Alaska

Natives for diabetic retinopathy through a collaborative project with the Joslin Diabetes Center using the

Joslin Vision Network (JVN). The JVN is a telemedicine system that uses low-level illumination and no

pupil dilation to remotely diagnose diabetic

retinopathy. The acquired retinal image is sent electronically to a reading center using existing IHS networks, and an analysis of the level of diabetic

retinopathy is returned to the remote site. The IHS

has deployed imaging sites at the Phoenix Indian

Medical Center (PIMC), Sells PHS Indian Hospital,

Tuba City Indian Medical Center, Parker Indian

Hospital, Hopi Health Care Center, and the Chief

Andrew Isaac Health Center in Fairbanks, Alaska.

Certified readers at the IHS/JVN National Reading

Center in Phoenix evaluate the images acquired from

these sites. Since entering its clinical phase, the program has evaluated more than 1,500 patients who

had not currently met the prescribed level of care.

Many of these required referral due to a dangerous

level of diabetic retinopathy or other ocular pathology. Controlled study of this initial outcome indicates

that this telemedicine system can markedly increase

the annual diabetic retinopathy examination rate.

The most mature deployment site increased its 

examination rate from 47 percent to more than 70

percent in less than 1 year. Ten to fifteen additional

sites will be deployed during the next year at locations throughout Indian country. Primary challenges

to future site development in remote locations

include availability of clinical space and staffing. As

of December 2003, 13 deployment sites are classified

as active, 3 sites are inactive due to staffing difficulties, and 5 sites are scheduled for deployment in

January 2004. Clinical effectiveness has been demonstrated in a 3 percent overall increase in eye exam

rates at deployment sites from baseline measures

established in 2002. In addition, a central office for

all administrative, reading, and training activities

was established at PIMC. New enhancements of 

the project include the development of an IHS/JVN

Teleophthalmology website, a new software application that surveys the RPMS Patient Scheduling 

database to identify patients with diabetes who 

have an appointment for care but have not had an

eye examination within the previous 400 days, and 

a portable IHS/JVN system for deployment at

sites/areas with a diabetic population that is not

practically served by a fixed IHS/JVN deployment.

In addition to the Joslin Vision Network, the IHS 

NDP is partnering with the Joslin Diabetes Center 

to develop a web-based system that is based on the

case management model that tracks diabetes care

and education called the Comprehensive Diabetes

Management Program (CDMP). Its components

include a Clinical Assessment Module, a Behavioral

Assessment Module, and an Education/Reinforcement Module. Healthcare professionals on this 

workgroup comprise clinicians and educators who

specialize in diabetes care and education and represent Joslin, IHS, the Department of Defense, and the

Veterans Administraion. The CDMP will be integrated

with the IHS electronic medical records system database. Beta testing of the Clinical Assessment Module

and the Behavioral Assessment Module at Walter

Reed Medical Center began in January 2003. The

Nutrition Assessment Module is in development with

planned completion by the end of calendar year 2003.

The Phoenix Indian Medical Center (PIMC), IHS

Information Technology Support Center, IHS/JVN,

the IHS National Diabetes Program, and Joslin are

collaborating to deploy CDMP at PIMC in January 

or early February 2004. PIMC is the pilot site. In

2004, following the pilot testing, there will be alpha

testing of CDMP at an additional 3–5 sites in two IHS

Areas, and then a beta testing of CDMP in an additional 3–5 sites in three IHS Areas.

NIDDK/IHS/TLDC/AIHEC Collaboration to Recruit

AI/AN Students into Biomedical Science Research

DMICC ANNUAL REPORT 33 FY 2003
and Diabetes Careers. In FY 2001, at the request of

Tribal leaders serving on the Tribal Leaders Diabetes

Committee (TLDC), the IHS and the National Institute

of Diabetes and Digestive and Kidney Diseases

(NIDDK) collaborated on a project to encourage young

AI/AN students to consider careers in biomedical

research and diabetes. This project also involves 

the CDC and the American Indian Higher Education

Consortium (AIHEC), which represents the 34 Tribal

colleges around the country. An RFA was released 

in spring FY 2002 on this interagency collaborative

project designed to increase diabetes knowledge

among American Indian/Alaska Native students

through a multicultural diabetes-based science education curriculum for grades K–8 and high schools.

By engaging American Indian/Alaska Native youth in

the biomedical sciences at an early age in a culturally sensitive manner, a goal of increasing the number

of American Indian/Alaska Native health science 

professionals can hopefully be achieved. Eight planning grants, have been awarded to AIHEC institutions throughout Indian Country. In 2003, Phase 2—

the Curriculum Development and Pilot Testing

Phase—has begun. Funded Tribal colleges are developing K–4, 5–8, and 9–12 parallel curricula. These

curricula will be pilot tested in selected K–12 schools

and revised for fielding in all K–12 schools in

American Indian and Alaska Native communities in

subsequent years.

CDC/IHS Collaboration on Redesign of the National

Diabetes Prevention Center (NDPC). In FY 2001 and

FY 2002, a collaborative IHS NDP/CDC NDPC strategic action planning process laid the foundation 

for restructure and re-orientation for the National

Diabetes Prevention Center in Gallup, New Mexico.

This activity has ensured consistency with the

NDPC's original mission to provide diabetes outreach, information, and technical assistance to Tribes

throughout the United States. The NDPC's activities

for FY 2003 included gathering, connecting, and disseminating information about “what works” in diabetes care and prevention for all American Indian

and Alaska Native communities. Presently, the NDPC

is working in collaboration with the IHS NDP and 

its partners to pilot and distribute a variety of userfriendly tools such as AI/AN adaptations of the

CDC's CDCynergy, Diabetes Today, and Taking Care of

Your Diabetes. Data approaches to assist in diabetes

care and prevention efforts such as GIS mapping of

diabetes complications and a series of reports about

“what works” in information technology has been

packaged in a CD–ROM format for distribution to

health care leaders in Tribal communities.

The Tribal Leaders Diabetes Committee continued to

provided valuable advice and guidance during this

past year specifically on the Diabetes Education in

Tribal Schools Project, a joint project of NDPC, NDP,

NIH, and the American Indian Higher Education

Consortium to develop a diabetes science-based

national curriculum for Tribal schools.

In addition to collaboration with IHS NDP, the 

NDPC has engaged in projects with American Indian

Research and Education Centers at the University 

of Nevada at Las Vegas and the University of New

Mexico on the development of data software programs for collection and analysis, and support for

development of the Associate of Science curriculum

in diabetes prevention.

IHS NDP continues to collaborate with NDPC on 

the development and printing of educational

resources such as the IHS NDP Health for Native Life

magazine. This popular publication is developed for

members of Tribal communities who have diabetes

and their family members. The focus is on individuals who have diabetes and the various educational

topics around treatment, care, and education and

community-related support systems and activities.

The most recent issue has focused on individual and

Tribal fitness programs, support for persons with

diabetes, and self-care tips. Distribution is to I/T/U

grant programs, facilities, and Tribal organizations

nationwide. In addition, collaborative efforts have

resulted in the development of a 90-Day Journal for

Wellness for American Indian and Alaska Native 

individuals who wish to record a daily record of selfcare activities.

DMICC ANNUAL REPORT 34 FY 2002
Plans include completion of a video on Community

Health Workers, determining feasibility of a documentary on diabetes in AI/AN communities, and 

developing new partnerships such as with the

National Indian Youth Leadership Program.

The CDC Division of Diabetes Translation provides

diabetes epidemiologic support to the IHS National

Diabetes Program with one full-time position and

close collaboration on projects of mutual concern.

Committee on Native American Child Health

(CONACH). The IHS National Diabetes Program 

collaborated with the American Association of

Pediatrics CONACH and Section on Endocrinology 

to develop a new clinical report “Prevention and

Treatment of Type 2 Diabetes Mellitus in Children,

With Special Emphasis on American Indian and

Alaska Native Children.” This article appeared in 

the electronic pages of the October 2003 Pediatrics

journal. This report calls on pediatricians to aggressively work to prevent and treat type 2 diabetes in

AI/AN children, as these children face a higher risk

of contracting the disease than do children of other

ethnicities. According to the report, prevention programs in these communities require a cooperative

effort by pediatricians and other health care professionals, along with appropriate Tribal authorities,

schools, communities, State and Federal agencies,

and local businesses. The report also calls for more

research, prevention efforts, and treatments for children with type 2 diabetes. This clinical report is an

important guideline for both IHS and other health

providers seeing AI/AN children.

Collaboration and Partnership With Other Federal

Agencies and Organizations. Activities Include:

• IHS NDP Director serves as a member of the

Translation Committee of the Diabetes Prevention

Program, an NIH-sponsored study showing that

type 2 diabetes can be prevented.

• IHS NDP Director serves as a member of the

Steering Committee of the National Diabetes

Education Committee, a joint effort of the 

NIH and CDC to promote national awareness 

about diabetes.

• IHS NDP supports the American Diabetes

Association's outreach initiative program for

American Indian/Alaska Native communities:

Strong in Body and Spirit. Provides expert guidance related to diabetes program development and

modification based on participant evaluation.

• IHS NDP participates in the American Indian 

subcommittee of the National Diabetes Education

Program. The IHS NDP provides regular representation to the committee and helps with the 

formulation and distribution of program materials.

• IHS NDP participates in the Diabetes in Children

and Adolescents Work Group of the National

Diabetes Education Program. The IHS NDP 

contributed to the development of the Diabetes in

Schools Guide and will assist in its dissemination

to schools serving AI/AN students.

• A key partnership has been established with the

American Indian Higher Education Consortium

(AIHEC) Board to help build Tribal college and 

university capacity and infrastructure for 

diabetes training and program activities in 

AI/AN communities.

• Several IHS Area Diabetes Programs have partnered with CDC’s State Diabetes Control Programs

(e.g., Montana, Alaska, California, New Mexico) to

share skills, resources, and training.

DMICC ANNUAL REPORT 35 FY 2003
Future Activities

• In 2004 the IHS NDP will develop a competitive

grant program within the SDPI focused on primary

prevention of type 2 diabetes CVD (cardiovascular

disease) risk reduction in AI/AN with diabetes. A

Diabetes Collaborative approach, based on the

model used by the Bureau of Primary Health Care

at HRSA, will be used to implement these interventions in 40–60 AI/AN communities.

• IHS NDP will continue to conduct further in-depth

evaluation and validation studies and key informant interviews of Special Diabetes Program for

Indians grant program activities, as well as dissemination of successful grant program strategies.

• IHS NDP will continue to work with partners 

and Tribes to implement and fine-tune culturally

acceptable screening approaches for AI/AN 

communities.

• IHS NDP will continue to develop and provide 

more technical assistance and training (for health

professionals, Tribal leadership, administrators,

paraprofessionals, and patients) and promote

increased awareness regarding new diabetes 

prevention findings through media, booklets,

Internet, and other avenues of communication.

• IHS NDP will lead the effort in partnering with 

the American Indian/Alaska Native Boys and Girls

Clubs and the National Congress of American

Indians (NCAI) to promote healthy lifestyles for

children and youth aimed at reducing the risk for

early onset of diabetes in youth.

• IHS NDP will continue to promote data improvement through implementation of an enhanced 

electronic medical record specific to diabetes to be

used IHS-wide, development of an electronic medical records audit, centralized technical support 

for the Diabetes Management System of the IHS

electronic medical record, and ongoing collaboration with and support for a Diabetes Collaboration

amongst the Tribal Epidemiology Centers.

• IHS NDP will continue to focus efforts on dissemination of information on the Medicare Part B

Medical Nutrition Therapy (MNT) and Diabetes

Self-Management Training (DSMT) benefits to I/T/U

health care facilities. Seeking reimbursement for

MNT and DSMT will have far-reaching benefits 

for Tribes and Tribal communities by increasing

access to diabetes education and nutrition services. Increased access not only benefits those with

diabetes and/or pre-dialysis kidney disease, but

also expands opportunities for lifestyle interventions for the primary prevention of diabetes and

other chronic diseases.

DMICC ANNUAL REPORT 36 FY 2003
National Center for Complementary and

Alternative Medicine (NCCAM)

http://nccam.nih.gov

The National Center for Complementary and

Alternative Medicine is dedicated to exploring complementary and alternative healing practices in the

context of rigorous science, training complementary

and alternative medicine (CAM) researchers, and disseminating authoritative information to the public

and professionals. To achieve its objectives, NCCAM

supports basic and clinical research on CAM, awards

grants to train researchers in CAM and sponsors a

variety of outreach activities. The diabetes-related

projects that NCCAM is currently supporting reflect

its commitment to the clinical study of promising

CAM substances and modalities.

Current Activities

In Fiscal Year (FY) 2001, NCCAM and its cosponsors,

the NIH Office of Dietary Supplements and the

National Institute of Diabetes and Digestive and

Kidney Diseases (NIDDK) released a Program

Announcement (PA), “Chromium as Adjuvant Therapy

for Type 2 Diabetes and Impaired Glucose Tolerance.”

As a result of this PA, in FY 2003, the Center funded

a project that is investigating the effects of daily

chromium for 6 months at two dose levels on serum

measures of glucose tolerance and on endothelial

function in adults with impaired glucose tolerance.

The Center continues to support a study investigating the biochemical basis for chromium

enhancement of insulin action.

Other diabetes-related research includes a new 

pilot study of Maharishi Vedic medicine, which will

determine the feasibility, acceptability, and safety 

of implementing a multimodality intervention for

newly diagnosed type 2 diabetics while assessing

efficacy on glycemic control. Another pilot study 

will examine the effect of yoga on cortisol levels 

and glucose control in diabetes. Also being studied

is whether acupuncture improves impaired gastric

emptying in diabetic rats. NCCAM continues to support basic studies in: (1) examining the mechanisms

by which Ginkgo biloba may accelerate pancreatic

function and reduce glucose metabolism, and (2)

identifying the anti-hyperglycemic constituents of

Panax ginseng berry and the synergistic effects

between these constituents.

NCCAM’s Division of Intramural Research established a Diabetes Unit in April 2002. Its primary

research goal is to understand the molecular 

mechanisms of insulin action and insulin resistance

and the contribution of various CAM modalities to

the diagnosis, prevention, treatment, and cure of 

diabetes, obesity, and their vascular complications.

The Diabetes Unit currently has three active clinical 

protocols. One protocol is developing simple methods for assessing insulin sensitivity and insulin

secretion in vivo in humans. The other two protocols

are investigating effects of oral vitamin C and oral

glucosamine on insulin sensitivity and vascular

function in diabetic, obese, and healthy subjects.

The Diabetes Unit is also pursuing a number of 

laboratory-based projects to evaluate the role of

dietary supplements DHEA and carnitine to modulate metabolic and vascular actions of insulin and

adiponectin in adipose cells and endothelial cells.

Other studies are evaluating cross-talk between

inflammatory signaling pathways and metabolic

insulin signaling to understand the molecular 

mechanisms of insulin resistance.

In 2003, one percent of the NCCAM clearinghouse

inquiries were related to diabetes and CAM therapies. The NCCAM web site provides links to informative fact sheets on diabetes and CAM.

Future Activities

The PA “Chromium as Adjuvant Therapy for Type 2

Diabetes and Impaired Glucose Tolerance” is still

posted on the NCCAM web site and continues to generate interest from the research community. Further,

NCCAM encourages researchers to submit investigtor-initiated applications related to diabetes.

DMICC ANNUAL REPORT 37 FY 2003
National Center for Health Statistics (NCHS), CDC

http://www.cdc.gov/nchs

The mission of the National Center for Health

Statistics, as it relates to diabetes, is to monitor and

provide national diabetes statistics in the form of

summary health measures, as well as, individual and

healthcare encounter level data for research. This

information originates from vital records, interview

and examination surveys, medical records, and

patient encounters.

Current Activities

During 2003, NCHS continued to improve the

Nation’s understanding of the impact of diabetes 

by collecting new data on diabetes, preparing current

statistics on diabetes trends, and publishing collaborative study findings on diabetes. Examples of these

accomplishments include:

• Implementing a new U.S. Standard Certificate of

Live Birth that, when fully in place in all States,

will provide data to distinguish pre-pregnancy 

diabetes from gestational diabetes and to assess

the relationship of maternal weight gain to other

pregnancy risk factors, such as, diabetes.

• Collecting National Health Interview Survey 

(NHIS) data on preventive health care among people with diabetes, with support from the National

Institute of Diabetes and Digestive and Kidney

Diseases (NIDDK).

• Releasing National Vital Statistics data on diabetes-related mortality.

• Collaborating with the Centers for Disease Control

and Prevention (CDC) Division of Diabetes Translation (DDT) to release the first national data from

the National Health and Nutrition Examination

Survey (NHANES) on lower extremity disease

among diabetic adults.

• Publishing a new section on diabetes in the 2003

edition of Health, United States Chartbook on

Trends in the Health of Americans.

• Issuing a new publication, Health Care in America:

Trends in Utilization, which presents National

Health Care Survey (NHCS) data that documents

the increase in use of hospital and physician services, as well as, medications for diabetes.

• Preparing jointly, across multiple public and

private organizations, the 2003 National Diabetes

Fact Sheet.

• Conducting and publishing a study on the relationship between glucose impairment to cancer 

mortality.

• Collaborating with the Agency for Healthcare

Research and Quality to present National Health

and Nutrition Examination Survey (NHANES) 

data on diabetes control and National Hospital

Discharge Survey data on diabetes-related complications in two reports to Congress: The National

Healthcare Quality Report and National Healthcare

Disparity Report.

• Presenting a Healthy People 2010 progress report

to Department of Health and Human Services

(DHHS) Assistant Secretary of Health on achieving

the national health objectives for diabetes.

Future Activities

National Center for Health Statistics (NCHS) will

release 2003 National Health Interview Survey data

on diabetes care and 2001–2002 National Health 

and Nutrition Examination Survey data on physical

exams in persons with diabetes.

DMICC ANNUAL REPORT 38 FY 2003
With support from CDC’s Division of Diabetes

Translation and NIDDK, the National Center for

Health Statistics will develop the 2005 NHANES 

protocol to examine a sample of Americans for prediabetes, undiagnosed and diagnosed diabetes,

and metabolic syndrome. This effort is designed to

include oral glucose tolerance testing, hemoglobin

A1c, and other measures of diabetes management,

including blood pressure and lipid levels.

Future research will include investigations of

NHANES data on lower extremity disease among diabetic persons and analysis of data from the National

Survey of Family Growth to assess maternal health of

women with gestational diabetes.

NCHS will continue to obtain information on diabetes-related hospitalizations, ambulatory care visits, and nursing home stays. These data characterize

trends in health care utilization for diabetes; delivery

of preventive care services, including counseling on

diet and exercise; diagnostic screening; services provided; medications; and diabetic-related complications, including those resulting in hospitalization.

National Center for Research Resources (NCRR)

http://www.ncrr.nih.gov

NCRR develops and supports research technologies

and shared resources that are critically important to

the research efforts directed at maintaining and

improving the health of our Nation’s citizens.

Selected highlights of NCRR-supported diabetes

research activities and future plans that relate to

diabetes are presented below.

Current Activities 

Now beginning their third year, the 10 NCRR-supported Islet Cell Resource (ICR) centers:

• Provided approved transplant programs throughout the country with approximately 35 million

clinical grade islets to treat 52 patients afflicted

with severe type 1 diabetes.

• Established procedures through which human

islets can be provided to qualified investigators

engaged in approved basic research.

• Are developing islet assays predictive of clinical

success via collaborative efforts between several

groupings of ICRs.

• Are optimizing culture, storage, and shipping conditions to increase the likelihood of successful

transplantation.

• Have enlisted the coordinating center to provide

administrative, bioinformatics, and biostatistical

support for laboratory studies and clinical programs that use ICR-generated islets nationwide.

• Are establishing an islet web-based processing

database to share information with the NIDDKsponsored Collaborative Islet Transplantation

Registry to enable one-time data entry and

decrease the reporting burden for investigators.

DMICC ANNUAL REPORT 39 FY 2003
The 82 General Clinical Research Centers (GCRCs)

and their satellites provide the infrastructure needed by diabetes investigators, who are funded by

NIH, private foundations, and corporations, to:

• Study normal and abnormal glucose metabolism,

diabetic complications, islet and whole pancreatic

transplantation, risk factors, epidemiology, genetics, and pharmaceutical interventions.

• Investigate the pathologic consequences of diabetes using high intensity MRI (magnetic resonance imaging).

• Develop novel treatments using continuous 

glucose sensors and insulin pumps.

• Determine the role of race and ethnicity, gender,

age, pregnancy, and patient education in diabetes

prevention and treatment.

Several of NCRR’s Science Education Partnership

Awards focus on diabetes, providing inquiry-based

educational programs for K–12 students and disseminating information about risk factors and prevention through local science centers and museums,

schools, churches, and community groups.

The NIH Clinical Loan Repayment Program enables

talented physicians to continue their clinical

research. NCRR sponsors eight such individuals

engaged in diabetes research.

The WiCell Research Institute received an NCRR

Human Embryonic Stem Cell Infrastructure grant to

expand and distribute human embryonic stem cells,

which may lead to new methods by which islet cells

can routinely be generated for subsequent transplantation into diabetic patients.

The Shared Instrumentation Grant program provided

funds for mass spectrometers, flow cytometers, phosphoimagers, and DNA sequencers to support diabetes

research.

Diabetes-related research is being supported at five

NCRR-supported Research Centers in Minority

Institutions (RCMIs). Studies include:

• Self-care interventions for Hispanic and AfricanAmerican adults with diabetes.

• Use of an animal model to assess the effect of 

diabetes on ischemic brain damage.

• Relationship of Highly Active Anti-Retroviral

Therapy (HAART), and the increasing prevalence 

of diabetes in AIDS patients.

• Establishment of a twin registry that allows the

study of metabolic and hereditary conditions.

• Glucohomeostasis and metabolism in type 2 diabetes and obesity, and behavioral aspects of nutrient selection in human diets.

• DNA sequencing and genetic linkage computational resources for determining genetic contributions

to the high incidence of diabetes in the PuertoRican population.

Several Research Facility Improvement Program

awards for construction and renovation of research

facilities will benefit diabetes research, such as:

• Establishment at the University of Missouri of a

major Center for Diabetes and Cardiovascular

Health and a National Swine Research and

Resource Center.

• Construction of both the Maryland MedStar

Research Institute of Minority and Women's

Health Core Laboratory and the Drew University

Life Sciences Center’s Biomedical Research Unit

will allow the study of the natural history and

treatment of diseases that disproportionately

affect minorities, such as diabetes.

DMICC ANNUAL REPORT 40 FY 2003
Through the Institutional Development Award (IDeA)

Program, research on diabetes and its complications

continues through the study of:

• Hereditary, behavioral, and cultural elements that

contribute to the observed increase in diabetes risk

factors, such as obesity, among Alaska Natives.

• Diabetic retinopathy to aid understanding of diabetes-associated retinal degeneration.

• Whether antioxidant treatment of pregnant diabetic mothers decreases the rate of type 2 diabetes

in offspring.

• The role of an enzyme, human alkaline phytoceramidase, in regulating the formation of new blood

vessels from pre-existing ones, which might yield

new strategies to treat angiogenesis-related diseases, such as diabetic retinopathy.

• Diabetic oral health, focusing on periodontal disease, immune function, and glycemic control and

pilot testing an oral health educational program

for African Americans.

• The effectiveness of physical activity intervention

among African-American women with hypertension, including type 2 diabetes.

• The use of gene therapy to counter the deleterious

effects of oxidative stress on major regulatory signaling pathways in vascular smooth muscle and

endothelial cells in a mouse diabetic vascular 

disease model system.

Research model programs benefit the following diabetes research:

• Establishment of a Type 1 Diabetes (T1D)

Repository at The Jackson Laboratory to serve as a

distribution resource for mouse strains, to cryopreserve sperm and embryos, and to disseminate

information through a web site.

• Development and characterization of rat strains

that demonstrate very significant differences in

aerobic capacity, adiposity, glucose metabolism,

and insulin resistance.

• Investigation of the success and functionality of

pancreatic islet cell allograft survival in macaques

and baboons, as well as xenografts of islet cells

from pigs to diabetic macaques.

• Establishment of the National Swine Research and

Resource Center to serve as a central resource for

depositing, maintaining, preserving, and distributing swine models.

A research group at the University of Texas

Southwestern Biomedical Magnetic Resonance

Facility determined glucose metabolism via three

pathways: gluconeogenesis from glycerol, glycogenolysis, and gluconeogenesis from the citric acid cycle.

Future Activities 

An RCMI Clinical Research Network (RCRN) will

support the performance of clinical trials and other

research that addresses ethnic health disparities.

The RCRN will be comprised of the five RCMI clinical research centers and basic scientists at RCMI

sites with expertise in genomics, proteomics, imaging, and health outcomes research.

DMICC ANNUAL REPORT 41 FY 2003
NCRR, in collaboration with the National Institute 

of Arthritis and Musculoskeletal and Skin Diseases

(NIAMS), National Center on Minority Health and

Health Disparities (NCMHD), National Institute of

Diabetes and Digestive and Kidney Diseases (NIDDK),

National Heart, Lung, and Blood Institute (NHLBI),

National Eye Institute (NEI), National Institute on

Aging (NIA), and National Institute on Drug Abuse

(NIDA), will continue Clinical Research Education

and Career Development support of diabetes-related

research and training at Meharry Medical College,

the University of Puerto Rico, Medical Sciences

Campus, and Charles R. Drew University of Medicine

and Science.

NCRR will continue efforts to develop the nonhuman primate model for diabetes, using molecular

tools to search for naturally occurring diabetes 

in non-human primates and to detect genetic 

predisposition.

National Center on Minority Health 

and Health Disparities (NCMHD)

http://ncmhd.nih.gov

Statistics show that racial and ethnic minority populations constitute about 25 percent of adults with

diabetes in the United States. African Americans,

Hispanic/Latino Americans, American Indians, and

some Asian Americans and Native Hawaiians and

other Pacific Islanders are at particularly high risk

for type 2 diabetes.

The purpose of the National Center on Minority

Health and Health Disparities is to promote minority

health, as well as to lead, assess, and support 

the National Institutes of Health’s (NIH’s) effort to

reduce and ultimately eliminate health disparities.

The NCMHD is primarily responsible for coordinating all minority health and health disparities

research conducted or supported by the NIH. The

NCMHD supports basic, clinical, social, and behavioral research; promotes research infrastructure

development and training; fosters emerging programs; disseminates information; and reaches out to

minority and other health disparity communities.

The NCMHD is addressing health disparities in

racial and ethnic minorities with respect to diabetes

through the support of research in three broad

areas: preventing or delaying the early onset of 

diabetes through diabetes education and lifestyle

changes; improving the management of and therapies for diabetes; and the identification of biological

and genomic risk factors for diabetes. In FY 2003,

the NCMHD supported over 30 diabetes-related 

projects. NCMHD is committed to supporting diabetes research and training in partnership with

other NIH Institutes and Centers, particularly the

National Institute of Diabetes and Digestive and

Kidney Diseases (NIDDK), as well as other Federal

agencies such as the Centers for Disease Control 

DMICC ANNUAL REPORT 42 FY 2003
and Prevention. The NCMHD’s programs such as the

Centers of Excellence (Project EXPORT) and Loan

Repayment Program also offer opportunities for

institutions and individuals to assist the NCMHD 

in addressing diabetes.

The Centers of Excellence (Project EXPORT) program,

promotes the conduct of minority health and/or

health disparities research; the participation of

members of health disparity populations in biomedical and behavioral research, prevention, and

intervention activities through education and training; and builds research capacity in minorityserving institutions. Through Project EXPORT, the

NCMHD supports approximately 33 projects that

focus on diabetes among health disparity populations; 18 of those are new awards.

The Loan Repayment Program (LRP) offers two 

specific programs, the Loan Repayment Program 

for Health Disparities Research and the Extramural

Clinical Research Loan Repayment Program, which

are aimed at attracting a number of highly qualified

health researchers with an interest in health disparities or individuals from disadvantaged backgrounds

to pursue clinical research careers. Four LRP awards

were to researchers focusing their work on diabetes.

Current Activities

The Oklahoma Native American EXPORT Center at

the University of Oklahoma Health Sciences Center

focuses on reducing health disparities in Native

Americans, with an emphasis on diabetes prevention

and health promotion strategies aimed at children

and adolescents. Community outreach activities

include disseminating information on the epidemiology, intervention, and prevention of diabetes and

obesity to American Indian communities; encouraging and preparing communities; to participate in scientific studies of health; and providing science education opportunities to American Indian high school

students.

The Teamwork in Research and Intervention to

Alleviate Disparities (TRIAD) Project at the University

of North Carolina at Greensboro is aimed at developing and enhancing research infrastructure and 

partnerships to address major health disparities 

of African Americans, Hispanics, and low-income

children and adults in central North Carolina.

Components of the TRIAD Project are interdisciplinary/interagency, interactive, and synergistic to

ensure comprehensive efforts to address HIV/AIDS,

cardiovascular disease, and diabetes and their related risk factors. The anticipated short-term outcome

is an increased quality and quantity of prevention

and risk avoidance research, training, and outreach

efforts to eliminate health disparities. The overarching goal is to assist the community, region, and State

in meeting the critical health needs of a rapidly

increasing, diverse citizenry in a culturally and linguistically competent manner through research,

training, and outreach.

The Columbia Center for the Health of Urban

Minorities (CHUM) at Columbia University will build

on existing research programs to develop an interdisciplinary center of research in minority health

and health disparities. The research focus of CHUM

will be access to care. One research core will focus

on primary (financial) barriers to care, and other

cores will focus on non-financial barriers in four

specific areas: cardiovascular disease, mental health,

diabetes, and injury and disability prevention. A

Community Planning Council will be created and

will work with a public health promotion specialist

to facilitate collaboration between the community

and the academic health center. CHUM will also 

support the training and research career development of minority investigators and provide the 

university with a unique opportunity to develop 

and institutionalize a cross-cultural curriculum for 

medical students.

DMICC ANNUAL REPORT 43 FY 2003
National Eye Institute (NEI)

http://www.nei.nih.gov

The National Eye Institute’s mission is to conduct

and support research, training, health information

dissemination, and other programs concerned with

blinding eye diseases, visual disorders, mechanisms

of visual function, preservation of sight, and the special health problems and requirements of the blind.

Diabetes is responsible for diabetic retinopathy, an

eye disease that is the leading cause of blindness in

people between the ages of 24 and 70 years. This 

disease is characterized by a progressive breakdown

of the normal retinal vascular system.

Current Activities

The NEI has joined other NIH institutes in issuing

RFA DK-03-024, “Proteomics and Metabolomics in

Type 1 Diabetes and its Complications” to encourage

the scientific community to use proteomics technologies to study type 1 diabetes and its complications. The NEI has joined other NIH institutes in reissuing an RFA (DK-03-001) “Bench to Bedside

Research on Type 1 Diabetes and Its Complications”

with the goal of translating advances in the understanding of the molecular basis of type 1 diabetes

and its complications into new therapies for the 

prevention, treatment, and cure of this disease.

The NEI joined other NIH institutes in issuing 

RFA-DK-03-020, “Small Business Innovation

Research (SBIR) and Small Business Technology

Transfer (STTR) To Develop New Therapies for Type 

1 Diabetes and Its Complications” to encourage the

small business community to apply cutting edge

technology to research to develop new approaches 

to prevent, treat, and cure type 1 diabetes and its

complications.

NEI continues its interest along with the National

Institute of Diabetes and Digestive and Kidney

Diseases (NIDDK) in the genetic aspects of diabetic

retinopathy through PA-02-020 , “Strategies to

Identify the Genetic Basis of Diabetic Retinopathy,”

which alerts the scientific community to this continuing interest and encourages research on the genetic

basis of this disease. This Program Announcement

(PA) seeks a broad range of grant applications in

gene discovery, genetic epidemiology, methodological studies of phenotypic assessment of retinopathy,

including possible surrogate markers, and the 

development and application of novel statistical

methods relevant to analyzing genetic data on 

diabetic retinopathy.

NEI continues its collaboration with other NIH 

institutes and the American Diabetes Association

(ADA) on PA-02-153, “Translational Research for the

Prevention and Control of Diabetes.” This PA seeks

translation of recent advances in the prevention and

treatment of type 1 and type 2 diabetes into clinical

practice for individuals and communities at risk.

The NEI continues to participate with other NIH

institutes in a PA entitled “The Role of Antioxidants

in the Prevention of Diabetic Complications.” This 

PA focuses on the role of antioxidants in preventing,

delaying, or ameliorating the micro- or macrovascular complications of diabetes as well as the mechanism(s) by which antioxidants might prevent 

diabetic vascular disease.

NEI continues to participate with NIDDK, the

National Institute of Dental and Craniofacial

Research (NIDCR), the National Institute of

Neurological Disorders and Stroke (NINDS), and the

National Heart, Lung and Blood Institute (NHLBI)

in a program announcement (PA–99–159) on “The

Role of Growth Factors in the Development of 

Diabetic Complications.” This PA encourages grant

applications on the role of growth factors in the 

etiology and pathogenesis of the micro-and

macrovascular complications of diabetes.

NEI continues to co-sponsor ACCORD (Action to

Control Cardiovascular Disease Risk in Diabetes),

a large multicenter trial supported by NHLBI and

DMICC ANNUAL REPORT 44 FY 2003
NIDDK to assess treatments to reduce risk of 

cardiovascular disease in type 2 diabetes. For this

trans- NIH effort, NEI is sponsoring an eye examination with fundus photography at baseline and at 

4 years of follow-up to assess the effects of these

treatments on diabetic retinopathy in these patients.

Another initiative seeks to identify genetic associations in patients with microvascular complications

of diabetes. NEI continues to supplement the FIND

(Family Investigation of Nephropathy and Diabetes)

study funded by NIDDK to investigate the genetics 

of individuals and special populations of patients

with renal disease. NEI is supporting detailed eye

examinations for these patients and will search for

genetic associations with microvascular disease.

NEI is supporting the continuation of two NIDDKsupported clinical trials that are now follow-up

studies, the Diabetes Control and Complications

Trial/Epidemiology of Diabetes Interventions and

Complications Study (DCCT/EDIC) and Diabetes

Prevention Program/Diabetes Prevention Program

Outcomes Study (DPP/DPPOS). The eye component 

of these two studies are important outcomes in

these studies of systemic treatments for both the

prevention and the treatment of diabetes and its

complications such as diabetic retinopathy.

Under the National Eye Health Education Program,

the NEI completed its formative research with the

American Indian/Alaska Native community. This

research on diabetic eye disease is being used to

complete a communication plan on diabetic eye 

disease that will be implemented in 2004. Strategies

will include working with the Indian Health Service

and Tribal councils on diabetes. A series of community-based projects on diabetic eye disease were

implemented as part of NEI’s Healthy Vision

Community Awards Program. This program provides

support to communities addressing vision objectives

in Healthy People 2010. The NEI joined with the

National Urban League (NUL) to support five diabetic eye disease components of the NUL’s Lift Every

Voice Diabetes Program. Plans are underway to

develop a mass media, community-based promotion

on diabetic eye disease during May 2004, Healthy

Vision Month. A Spanish public service campaign

will be released during May. Through this effort,

NEI hopes to increase awareness about the importance of 

dilated eye exams for people with diabetes.

NEI continues support of the evaluation of new

treatments for diabetic macular edema, a major

cause of visual loss in patients with diabetes

through the Diabetic Retinopathy Clinical Research

Network (DRCRN). This network supports core 

centers to plan, implement, and conduct clinical 

trials on the treatment of diabetic macular edema.

The overall goal of this project is to develop an

infrastructure to accelerate the development and

conduct of clinical trials of the treatment of diabetic

macular edema. These include both medical and surgical approaches. Grant awards have been made for

a coordinating center in Tampa, Florida, a reading

center in Madison, Wisconsin, and a chairman’s

grant in Boston, Massachusetts. Over 100 clinical

centers have been identified as participants in the

network. A randomized clinical trial testing two different laser approaches for diabetic macular edema

has been started and another randomized, phase 3

clinical trial evaluating a novel intravitreal steroid

preparation for diabetic macular edema is planned

to begin in the second quarter of 2004.

Future Activities

NEI will continue to incorporate the scientific priorities outlined in the Report of the Congressionally

Established Diabetes Research Working Group in

making funding decisions. The National Eye Health

Eduction Program (NEHEP) will continue to develop

and implement outreach activities for people with

diabetes. NEI will continue to encourage experienced investigators from outside vision research to

apply their expertise to develop novel strategies for

increasing knowledge about the pathophysiology

and treatment of diabetic retinopathy.

DMICC ANNUAL REPORT 45 FY 2003
DMICC ANNUAL REPORT 46 FY 2003

National Heart, Lung and Blood Institute

(NHLBI)

http://www.nhlbi.nih.gov

The primary cause of death in patients with diabetes

is cardiovascular disease (CVD). NHLBI has continued to expand its comprehensive programs of basic

and clinical research to understand the pathogenesis, improve treatment, and develop effective prevention strategies to reduce or postpone the cardio-vascular complications of diabetes. Despite reductions

in CVD mortality in the general population, patients

with diabetes continue to have 2–4 times the CVD

rates of non-diabetics of the same age, gender, and

ethnic group. With increases in diabetes in the

United States, diabetes will become an increasingly

important cause of heart and vascular disease.

Current Activities

During the past year, NHLBI has continued work on

three major clinical trials that will evaluate several

therapeutic approaches designed to reduce cardiovascular complications of diabetes. The Action to

Control Cardiovascular Disease Risk in Diabetes

(ACCORD) trial successfully completed a 1,000

patient Vanguard phase and initiated recruitment 

for the main phase (9,000 additional patients). The

cohort will be followed over the next 5 years to 

evaluate the benefits of intensified control of hyperglycemia compared to conventional glucose control

and also will test the benefits of aggressive blood

pressure control and intensified control of the dyslipidemias associated with diabetes upon CVD rates.

The Bypass Angioplasty Revascularization Investigations II–Diabetes (BARI 2D) trial is recruiting 2,300

patients to evaluate whether elective coronary artery

revascularization plus optimal medical management

of cardiovascular risk factors and symptoms is superior to optimal medical management alone. It will

also evaluate the important issue of whether reducing insulin resistance provides protection against

CVD complications by testing whether insulin-sensitizing drugs are superior to injected insulin or to

oral drug regimens that stimulate insulin secretion

at 

levels of glycemic control that are attainable with

current conventional treatments. The National

Institute of Diabetes and Digestive and Kidney

Diseases (NIDDK) is providing partial support for

both of these trials. NHLBI is also helping to fund

the NIDDK-sponsored Action for Health in Diabetes

(Look AHEAD) trial, which is evaluating the effect of

obesity treatment on CVD complications in type 2

diabetic patients.

Taken together, these three trials should lead to new

clinical approaches that reduce cardiovascular complications of both type 1 and type 2 diabetes.

NHLBI also supports basic research to identify new

ways to treat and prevent the major vascular complications of diabetes. It is particularly important to

develop new therapies that can reduce the macrovascular complications of diabetes without requiring

intensive efforts at glucose control. NHLBI has

expanded basic research related to CVD complications of diabetes including continuation of several

large project grants originally cosponsored with the

Juvenile Diabetes Foundation.

NHLBI has also participated, alone and in collaboration with NIDDK, in the development and initiation

of a number of programs aimed at improved understanding of diabetic macrovascular complications.

These programs are: 

• Progression of Cardiovascular Disease in Type 1

Diabetes HL-04-013

http://grants2.nih.gov/grants/guide/rfa-files/RFAHL-04-013.html 

• Proteomics and Metabolomics in Type 1 Diabetes

and its Complications DK-03-024

http://grants.nih.gov/grants/guide/rfa-files/RFADK-03-024.html 
DMICC ANNUAL REPORT 47 FY 2003

• Innovative Partnerships in Type 1 Diabetes

Research DK-03-015

http://grants1.nih.gov/grants/guide/rfa-files/RFADK-03-015.html 

• Bench to Bedside Research on Type 1 Diabetes 

and Its Complications DK-03-019

http://grants1.nih.gov/grants/guide/rfa-files/RFADK-03-019.html 

• Small Business Innovation Research (SBIR) and

Small Business Technology Transfer (STTR) to

Develop New Therapies for Type 1 Diabetes and 

its Complications DK-03-020

http://grants1.nih.gov/grants/guide/rfa-files/RFADK-03-020.html

These programs have involved studies of the effects

of diabetes on vascular smooth muscle and endothelial cells, effects on circulating growth factors and

adhesion molecules, reactive oxygen species,

advanced glycated end products, and the effect of

salt restriction on insulin sensitivity. Grants have

also been awarded to elucidate the etiology of diabetes-associated cardiomyopathy, an abnormality

that contributes to the high rates of congestive 

heart failure in diabetic patients.

Other programs, through multidisciplinary research

efforts, attempt to delineate the role played by

hyperglycemia and insulin resistance in the genesis

of cardiovascular disease in diabetes. Hypotheses to

be tested include whether elevated glucose and/or

insulin resistance leads to accelerated cardiovascular disease by increasing oxidative stress and inflammatory signals in the vessel wall. Progress has been

made in elucidating the role of regulatory mechanisms of high glucose and fat (lipoxygenase) in 

initiating and accelerating atherosclerosis. The

results should increase our knowledge of the factors

leading to accelerated CVD in diabetes and lead to

new therapeutic advances.

With the goal of elucidating biochemical, metabolic,

and genetic mechanisms of macrovascular disease 

in insulin-dependent diabetes mellitus, NHLBI is

supporting programs to define how multiple pathological processes interact at the level of the arterial

wall to promote atherosclerosis. The investigators

are examining changes in the composition and 

modifications of lipoproteins, the effects of longterm protein glycation and oxidative stress, autoimmune responses to modified lipoproteins, and

changes in the kallikrein/kinin system, and testing

for mechanisms and interrelationships between

these factors using cell culture systems and in vivo

metabolic studies.

Other investigations include the biology of nuclear

receptors, as they serve as central integrators of

gene regulation to a variety of physiological and

pathophysiological stimuli. These studies should

provide significant new insights into mechanisms 

by which therapy could be designed to control specific abnormalities involved in diabetes and cardiovascular disease.

Additional investigations are examining the

proatherogenic effect of consumption of a high

glycemic load diet on the blood vessel walls and

blood clotting. Studies will provide much needed

information about the cardiovascular consequences

of some of the commonly used diets in order to properly advise individuals and the public at-large about

the long-term consequences of dieting.

NHLBI has also participated, in collaboration with

NIDDK, in the program of small, innovative grants

aimed at utilizing state-of-the-art gene therapy

approaches for treatment of diabetes and its complications. The information that will be gained with the

completion of these experiments will be significant

in the continued development of angiogenic factor

gene therapies, offering new technology that will

render the therapies safer for treating cardiovascular

ischemic disorders of diabetes.
DMICC ANNUAL REPORT 48 FY 2003

Finally, it is important to recognize that many of the

other research efforts supported by NHLBI may help

to reduce or improve treatment for cardiovascular

diseases occurring in patients with either type 1 or

type 2 diabetes. This is because the effect of diabetes

on macrovascular disease is, at least in part, to

accelerate progression of the underlying atherosclerosis that is also common in non-diabetic individuals in middle and older ages. Thus, studies on 

treatment of congestive heart failure, treatment of

arrhythmias, including public access to defibrillation, implantation of vascular stents that contain

drugs that reduce restenosis rates, regeneration of

cardiac muscle, and other treatments may have

major benefits for patients with diabetes.

Taken together, the clinical and basic studies

described should provide better guidance for physicians to reduce cardiovascular complications of 

diabetes in the near future and, in later years, lead 

to development of easier to use, more effective 

therapies.

National Human Genome Research Institute

(NHGRI)

http://www.nhgri.nih.gov

The National Human Genome Research Institute led

the National Institutes of Health’s (NIH) contribution

to the International Human Genome Project (HGP),

which had as its primary goal the sequencing of the

human genome. This project was successfully completed in April 2003. Now, the NHGRI’s mission has

expanded to encompass a broad range of studies

aimed at understanding the structure and function

of the human genome and its role in health and disease.

To that end, NHGRI supports the development of

resources and technology that will accelerate

genome research and its application to human

health. In the laboratories of the Division of Intramural Research (DIR), with the tools produced by 

the HGP, scientists are developing and using the

most advanced techniques to study the fundamental

mechanisms of inherited and acquired genetic 

disorders, including type 2 diabetes mellitus.

Current Activities

Finland–U.S. Investigation of NIDDM Genetics. Type

2 diabetes is one of the major causes of morbidity

and mortality in the developed world. While environmental factors such as diet play a significant

role, familial clustering indicates that there must 

be significant genetic susceptibility factors at work.

For the past 10 years, researchers at NHGRI have

been engaged in a large collaborative study known

as the Finland–United States Investigation of NonInsulin Dependent Diabetes Mellitus (FUSION), in

which over 5,000 individuals with diabetes and 

suitable controls from Finland are being studied,

using careful phenotyping of diabetes and diabetesassociated traits and genome-wide genetic linkage

and association. Researchers at NHGRI have developed new approaches in the laboratory to achieve

high-throughput microsatellite and SNP (single
nucleotide polymorphism) genotyping, which has

allowed the collection of a massive amount of data

from these Finnish diabetics and their families. This

project has made significant progress, focusing on

fine mapping of regions on chromosomes 6, 11, 14,

20, and 22, where prior linkage analyses have shown

evidence for susceptibility genes for diabetes or

related traits. In particular, researchers have identified a small region on chromosome 22 that contains

a haplotype conferring an odds ratio of 1.5 for type

2 diabetes and has been confirmed and narrowed 

by studying a West African diabetic population.

Researchers have also identified susceptibility 

variants in a small region of the promoter of an

excellent candidate gene on the long-arm of chromosome 20, a region where a dozen groups have 

independently shown evidence of linkage for 

type 2 diabetes. These variants seem to account 

for most or all of the linkage signal and have just

been confirmed in an independent study of

Ashkenazi diabetics.

Statistical Genetic Analysis of Traits Related to Type

2 Diabetes. Researchers at NHGRI are also analyzing

statistical genetic data on type 2 diabetes provided

by collaborators from the Genetics of NIDDM study

and GlaxoSmithKline suggesting candidate regions

on chromosomes 1 and 14 in Japanese Americans.

Other collaborators have provided genetic marker

data from these potential candidate regions in an

independent sample comprising 175 JapaneseAmerican families with a high prevalence of diabetes from a Hawaiian population. The goal of this

project is to attempt independent replication of

results in these potential candidate regions, with

further evaluation in the event of positive results.

In FY 2003, work on this project included statistical

linkage and association analyses in type 2 diabetes

with DNA markers in candidate regions on chromosomes 1 and 14. Evidence of both linkage and 

association was obtained in the candidate region 

on chromosome 14, constituting independent replication of previous results in this region. These

results provide additional support for the hypothesis that a susceptibility locus for type 2 diabetes

may reside in this candidate region on chromosome

14. Future plans include statistical analyses of DNA

markers in this candidate region using the expression level of adiponectin, a protein related to 

obesity and type 2 diabetes. The locus influencing

adiponectin level was independently mapped to 

the candidate region on chromosome 14, providing 

a possible mechanism for genetic susceptibility in

this population.

Cultural and Ethical Issues Associated with Genetic

Family Studies. The institute’s Ethical, Legal, and

Social Implications (ELSI) Program is designed to

provide a novel approach to scientific research by

identifying, analyzing, and addressing the ethical,

legal, and social implications of human genetics

research at the same time that the basic scientific

issues are studied. The ELSI Program is funding a

project that aims to examine cultural and ethical

issues associated with participation in genetic family studies by patients with a family history of type 2

diabetes mellitus, in order to enhance the ascertainment process and establish strategies for genetic

counseling of patients and relatives with a family

history of type 2 diabetes and diabetic neuropathy.

Technology Development for Natural Genetic

Variation. In FY 2002, NHGRI created a program 

to establish new academic Centers for advanced

genome research. These Centers of Excellence in

Genomic Science (CEGS) will support multi-investigator, interdisciplinary teams to develop innovative

genomic approaches to address biological problems.

One of the CEGS aims to develop tools for studying

natural genetic variation and to apply those tools 

to develop an improved understanding of the 

molecular basis of genetic susceptibilities to type 1

diabetes, progressive supranuclear palsy, and neutropenia. More broadly, the center expects, through

its development of new technology and close 

interactions between theory and experiment, to 

contribute indirectly to many research projects

directed at understanding the genetic contributions

to human health and disease.

DMICC ANNUAL REPORT 49 FY 2003
DMICC ANNUAL REPORT 50 FY 2003

National Institute of Allergy and Infectious

Diseases (NIAID)

http://www.niaid.nih.gov

The National Institute of Allergy and Infectious

Diseases supports a broad range of research on 

the immunopathogenesis of autoimmune diseases,

including type 1 diabetes. Basic research focuses 

on understanding the genetics of autoimmunity,

elucidating the mechanisms of self-tolerance, developing approaches to induce self-tolerance, and 

characterizing pathways of immune-mediated tissue

destruction. These studies provide the knowledge 

to develop new treatments and diagnostic tests for

autoimmune diseases, including type 1 diabetes, and

novel treatments for ongoing disease.

The NIAID chairs the NIH Autoimmune Diseases

Coordinating Committee (ADCC), established in FY

1998 at the request of Congress to increase collaboration and facilitate coordination of research among

NIH Institutes and Centers, other Federal agencies,

and private organizations. In 2002, the ADCC completed and submitted to Congress a comprehensive

strategic and collaborative research plan for

autoimmune diseases, which was mandated in the

Children’s Health Act of 2000 (P.L. 106-310). The

ADCC Research Plan is a comprehensive, long-term

agenda for autoimmune diseases research in 

epidemiology and burden of disease; etiology and

pathogenesis; diagnosis, treatment, and prevention;

and training, education, and information dissemination. The ADCC Research Plan highlights new programs and research areas in which future progress

will benefit all autoimmune diseases and facilitate

the translation of new knowledge into more effective

treatments and prevention strategies. Since submitting its report to Congress, the NIH ADCC has 

initiated a comprehensive inventory of NIH-supported initiatives and activities in autoimmune diseases

research to help identify areas of the plan that are

being addressed and those areas that may need

additional effort.

Current Activities 

The NIAID is committed to furthering the understanding of the immunopathogenesis of autoimmune

diseases, including type 1 diabetes, and to promoting the translation of basic research to clinical

applications. During the past year, the NIAID has

continued to expand its research program in type 1

diabetes. In FY 1999, NIAID established the Immune

Tolerance Network (ITN), an international consortium dedicated to the clinical evaluation of novel

tolerance induction approaches for autoimmune diseases, asthma and allergic diseases, and prevention

of graft rejection. The goal of these therapies is to

“re-educate” the immune system to eliminate injurious immune responses and graft rejection while preserving protective immunity to infectious agents. An

important aim of the ITN is to explore the immune

mechanisms underlying efficacy (or lack of efficacy)

of candidate approaches. The ITN is conducting

clinical trials of tolerance induction approaches for

multiple autoimmune diseases, including type 1 diabetes. Examples of the ITN-supported clinical trials

for type 1 diabetes include: 

• The ITN is conducting the “Edmonton Protocol,”

an experimental islet transplantation protocol for

brittle type 1 diabetes based on the approach pioneered at the University of Alberta. The ITN trial

will further assess the safety and efficacy of this

regimen; expand the capacity for islet preparation

and clinical transplantation at nine sites in the

United States, Canada, and Europe; establish the

baseline success rate for islet transplantation; 

and facilitate the evaluation of new tolerogenic

approaches for islet transplantation. In 2003, the

ITN plans to initiate enrollment in two clinical

studies to evaluate the potential for an antibody 

to CD52 or an antibody to CD3 to induce tolerance

to transplanted islet cells.
DMICC ANNUAL REPORT 51 FY 2003

• The ITN is developing therapeutic approaches for

the prevention and reversal of type 1 diabetes. The

ITN is currently recruiting new onset type 1 diabetics into two trials to evaluate the use of a

humanized anti-CD3 monoclonal antibody, which

showed promise in the Phase I trial. Another trial

giving insulin B chain with adjuvant in new onset

diabetics demonstrated safety and is currently

expanding recruitment. If this approach proves

safe without the induction of immunity to the

insulin B chain, further studies to test the ability

of this combination to interrupt the autoimmune

process in new onset or at-risk individuals 

will follow.

• ITN clinical trials have integrated studies aimed at

identifying the underlying mechanisms involved in

disease progression and therapeutic actions of the

treatment regimens. In 2003 the ITN established a

contract with The Wellcome Trust Sanger Institute

(U.K.) to sequence key areas of the NOD mouse

genome. The data will be deposited into Genbank

for use by the research community.

The ITN includes more than 80 basic and clinical

scientists and physicians from over 40 institutions

in the United States, Canada, and Europe, and is cosponsored by NIDDK and the Juvenile Diabetes

Research Foundation International (JDRF). More

information about the ITN is available at

http://www.immunetolerance.org.

The NIAID, in collaboration with multiple NIH

Institutes and Offices, has established several large

multidisciplinary research programs for autoimmune diseases, including type 1 diabetes: 

• Autoimmunity Centers of Excellence (ACEs) program, co-sponsored by NIAID, National Institute 

of Diabetes and Digestive and Kidney Diseases

(NIDDK), and Office of Research on Women’s

Health (ORWH), was renewed in 2003 and expanded to nine centers. The ACEs conduct clinical trials

and basic research on immune-based therapies for

autoimmune diseases, including type 1 diabetes.

The program enhances interactions between scientists and clinicians to facilitate the translation of

scientific research findings into medical applications. ACE investigators and NIAID representatives

form the Steering Committee, which met in

Bethesda in November. Protocols for clinical trials

in type 1 diabetes are under development.

• The Centers for Autoimmune Disease Prevention,

co-sponsored by NIAID, NIDDK, JDRF, National

Institute of Child Health and Human Development

(NICHD), and ORWH, focus on advancing knowledge for the prevention of type 1 diabetes and

other autoimmune diseases. The Prevention

Centers initiate and support pilot projects for the

rapid testing of new ideas and technologies with

potential application to prevention of autoimmune

diseases, including a cutting-edge comprehensive

longitudinal study of gene expression during the

development of diabetes in the NOD mouse.

• NIAID and NIDDK will co-sponsor the Request for

Applications (RFA), “Clinical Islet Transplantation

Consortium: Clinical Centers” (CITC) to perform

islet/beta cell transplantation studies in adult

type 1 diabetes patients. The consortium of investigators and institutions will develop and implement a program of single- and/or multi-center

clinical studies, accompanied by mechanistic 

studies, in islet transplantation (with or without

accompanying kidney transplantation) for the

treatment of type 1 diabetes. A complementary

RFA will establish a Coordinating Center to provide statistical support, data monitoring, and 

core laboratory support to the CITC.
DMICC ANNUAL REPORT 52 FY 2003

• NIAID and NIDDK reissued the RFA “Innovative

Partnerships in Type 1 Diabetes Research” to 

provide access to specialized expertise or technologies and facilitate the formation of interdisciplinary research partnerships to investigate

significant biological and medical problems associated with type 1 diabetes. This initiative 

provides for collaborative research partnerships

between independent principal investigators with

expertise in different aspects of type 1 diabetes.

Eighty-one applications have been reviewed.

• NIAID and NIDDK co-sponsored the RFA “Bench to

Bedside Research on Type 1 Diabetes and its

Complications” to support partnerships between

clinical and basic researchers to translate

advances in the understanding of the molecular

basis of type 1 diabetes into new therapies for the

prevention, treatment, and cure of this disease. A

total of 69 applications were reviewed for this

year’s initiative; 2 of the 10 funded applications

were assigned to NIAID. The Bench-to-Bedside initiative will be reissued in 2004.

• NIAID and NIDDK co-sponsored the RFA “Gene

Transfer Approaches to Enhance Beta-Cell

Transplantation” to support feasibility and pilot

projects for methods to engineer beta cells or alter

islets to enhance their viability. In FY 2003, NIAID

supported five R21 grants to investigate various

methods of genetically modifying islets or beta

cells to express molecules involved in immune

modulation and the effects of genetic modification

on tolerance induction and survival of islets after

transplantation. Successful completion of these

projects could provide important insights for more

efficacious treatment of type 1 diabetes.

Future Activities

NIAID will continue to support basic research and

clinical trials of promising therapeutic approaches

for multiple autoimmune diseases through the Autoimmunity Centers of Excellence (ACEs), the ITN, and

the Centers for Autoimmune Disease Prevention.

NIAID and NIDDK will co-sponsor “Clinical Islet

Transplantation Consortium: Clinical Centers”

(CITC) to perform islet/beta cell transplantation

studies in adult type 1 diabetes patients and a complementary RFA to establish a Coordinating Center

for the CITC to provide statistical, data monitoring,

and core laboratory support.
DMICC ANNUAL REPORT 53 FY 2003

National Institute of Biomedical Imaging and

Bioengineering (NIBIB)

http://www.nibib.nih.gov

The NIBIB will lead the development and application

of breakthrough technologies from science and engineering to establish a foundation to understand

complex biological processes and to improve health.

Consistent with its mission and vision, the NIBIB

supports diabetes-related research in the areas of

imaging, sensor technology, and telehealth.

Current Activities

The NIBIB, along with the National Institute of

Diabetes and Digestive and Kidney Diseases (NIDDK)

and the Juvenile Diabetes Research Foundation

International, held a workshop entitled, Imaging the

Pancreatic Beta Cell, in April 2003. The workshop

was effective in providing an overview of recent

advances in beta cell biology; summarizing new

approaches for cellular and molecular imaging; disseminating results of research supported under 

previous initiatives; fostering interactions between

beta cell biologists, imaging scientists, and engineers; and pointing to future applications of 

imaging techniques in understanding the natural

progression of diabetes and monitoring clinical

treatments for diabetes.

In FY 2003, the NIBIB issued three research solicitations relevant to diabetes—Operation of Sensors In

Vivo (EB-03-001), Research and Development of

Systems and Methods for Cellular and Molecular

Imaging (EB-03-003; co-sponsored by the National

Institute of General Medical Sciences (NIGMS)), and

Telehealth Technologies Development (PA-03-030).

The NIBIB also supports diabetes-related research

through investigator-initiated projects.

In the area of imaging, researchers are focusing on

the use of magnetic resonance imaging (MRI) as a

non-invasive tool to assess encapsulated transplanted islets for viability and the ability to secrete

insulin in response to changing glucose concentrations (this grant is supported under EB-03-003—

Research and Development of Systems and Methods

for Cellular and Molecular Imaging). NIBIB-supported scientists are also developing improved MRI

probes, high-resolution imaging, and novel imaging

techniques to measure responses to therapy and to

monitor the development of diabetic complications.

In the area of glucose sensors, NIBIB-supported

researchers are striving to improve the technology

both for implanted sensors and non-invasive sensors. For example, advances in miniaturization and

magnetic field technology are enabling scientists to

explore the design of a sensor to measure certain

compounds in saliva. In related work, researchers

have developed, and are working to refine, a noninvasive glucose sensor using an iontophoretic

approach to pass a low level electrical current

through the skin to obtain measurements of glucose

and other compounds. Investigators are also

improving the technology for implantable glucose

sensors to improve responsiveness and to extend

their functional lifetime.

Obesity and type 2 diabetes are emerging epidemics

in the United States. A modest weight loss has been

proven to reduce the risk for developing diabetes

and can reduce or eliminate the need for anti-diabetic medications. However, the implementation of

behavioral weight loss programs in a primary care

setting is challenging. While Internet-based weight

loss programs are effective, access to personal 

computers may be limited especially in the elderly

and low-income populations. Investigators supported through PA-03-030 (Telehealth Technologies

Development) will develop an interactive diet and

exercise program to be conducted with patients in

their own home via a television set. Success in this

endeavor would result in a convenient, intuitive,

and inexpensive way to conduct large-scale interventions to combat obesity and type 2 diabetes.
DMICC ANNUAL REPORT 54 FY 2003

Other investigators supported through PA-03-030

are exploring the development of various Internetor cable television-based interactive monitoring 

and educational systems for chronic diseases,

including diabetes.

Future Activities

During FY 2004, the NIBIB will issue a program

announcement for the micro-imaging of pancreatic

islets. In addition, the NIBIB will also co-sponsor a

workshop in islet encapsulation along with the

National Institute of Diabetes and Digestive and

Kidney Diseases and the Juvenile Diabetes Research

Foundation International.

In summary, the NIBIB is developing a robust

research program in biomedical imaging and bioengineering that will focus on developing fundamental new knowledge, fostering potent new 

technologies, nurturing and supporting promising

researchers, and facilitating cross-cutting capabilities. Within its research mission, the NIBIB will continue to support technology-driven research to further advance all areas of diabetes-related research

and to translate these discoveries to improve the

health of individuals with diabetes.

National Institute of Child Health and 

Human Development (NICHD)

http://www.nichd.nih.gov

The mission of the National Institute of Child Health

and Human Development is to promote the development of healthy children. Understanding genetic 

and environmental factors that contribute to the

development of diabetes is consistent with this 

mission, given the prevalence of both type 1 and type

2 diabetes in children and the serious complications

of diabetes later in life. The NICHD focuses its efforts

on the earliest pathogenesis of type 1 diabetes and

on optimizing insulin therapy in children with type 

1 diabetes. In addition, NICHD supports research on

the origins of type 2 diabetes in adolescents and on

improving the outcome of pregnancy in women with

gestational diabetes mellitus.

Current Activities

In efforts to prevent type 1 diabetes, the NICHD 

pioneered methods in stratifying levels of risk for

type 1 diabetes mellitus according to genetic and

immunologic markers. This work forms the basis of

a collaboration with the Juvenile Diabetes Research

Foundation (JDRF) to co-fund two large prospective

studies of infants who have relatives with type 1

diabetes in order to ascertain the earliest immunologic changes in the pathogenesis of type 1 diabetes.

The incidence of type 1 diabetes has increased

steadily over the past 30 years. It is presumed that

environmental factors account for this striking

increase in incidence. Epidemiologic studies and

animal models implicate cow milk antigens in infant

formula as an environmental agent that may trigger

an autoimmune attack on the beta cells of the pancreas. In order to test this hypothesis, the NICHD 

is supporting an international randomized controlled clinical trial. Screening began in FY 2002 to

enroll 2,000 infants at high genetic risk of type 1

diabetes, based on family history and HLA genotype.

The infants are randomized to standard infant 

formula or to Nutramigen®, a casein hydrolysate.

The investigators are documenting the development 
DMICC ANNUAL REPORT 55 FY 2003

of autoantibodies in these children. Mead-Johnson

is providing the standard formula and the

Nutramigen®. The study is funded by the NICHD, the

JDRF, the Canadian Institutes of Health Research,

the European Foundation for the Study of Diabetes,

and the Netherlands Diabetes Foundation. Specially

appropriated type 1 diabetes research funds are

also being used to support the project. These funds

are administered by the NIDDK.

The NICHD is currently supporting a 15-site,

prospective, international study of hyperglycemia

and adverse pregnancy outcomes. The investigators

of this study of gestational diabetes mellitus are in

the process of enrolling 25,000 women early in their

pregnancy. These women will be followed through

their gestation, delivery, and postpartum period.

Their infants will be studied as well. The NIDDK 

is co-funding this landmark study.

Congressional Report 106-293 encourages the

NICHD to work with the National Institute of

Allergy and Infectious Diseases (NIAID) and NIDDK

on efforts to develop a vaccine to prevent juvenile,

or type 1 diabetes. In response to this Report,

NICHD joined the NIDDK in co-funding TrialNet, a

Network of 14 centers designed to perform clinical

trials of new immunomodulatory agents to treat,

delay, or prevent the onset of type 1 diabetes. The

NICHD also joined the NIDDK and the NIAID in 

co-funding the Cooperative Study Group for Autoimmune Disease Prevention, a network of investigators who are developing new methods to induce

immune tolerance to self-antigens of the beta cells

of the pancreas. Ultimately, this collaborative

research promises to mitigate or reverse the autoimmune process that leads to type 1 diabetes.

The NICHD supports a cooperative multicenter

research network consisting of five clinical centers

and a coordinating center. The mission of the

Diabetes Research in Children Network (DirecNet) is

to investigate the potential use of glucose monitoring technology and its impact on the management 

of type 1 diabetes in children. Funding, initiated in

September 2001, was received from specially appropriated funds for research in type 1 diabetes.

Specific goals for the network include the assessment of the accuracy of continuous monitoring

devices in order to determine if these are useful in

improving glycemic control and preventing hypoglycemia in diabetic children. Additional goals are

to determine the optimal utilization of continuous

glucose monitors in the management of diabetes in

children and to assess the impact of continuous 

glucose monitoring on quality of life for the child

and family. DirecNet has recently published glucose

monitoring accuracy studies in two articles appearing in the November 2003 issue of Diabetes

Technology and Therapeutics. Additional accuracy

protocol findings, specifically studying the monitoring systems during hypoglycemia, will soon be 

published in Diabetes Care.

The Intramural Research Program of the NICHD is

following children in a 15-year study designed to

understand the earliest pathogensis of insulin

resistance and glucose intolerance in obese children

and in non-obese children of obese parents. In two

randomized clinical trials, these investigators are

also studying the effects of metformin and orlistat

in obese insulin-resistant children. An important

intramural study is now underway that is designed

to develop ways to improve glycemic control in children with type 1 diatbetes.

Future Activities

DirecNet is currently recruiting subjects for an outpatient randomized controlled study examining 

continuous glucose monitoring systems vs. conventional care using conventional monitors in diabetic

children. Furthermore, a protocol examining the use

of continuous glucose monitors during exercise is

currently in development. In response to a newly

released RFA (Request for Applications) on establishing the precursors of the metabolic syndrome in 

children, the NICHD in conjunction with the NIDDK

plans to fund new studies designed to ascertain the

earliest origins of insulin resistance and glucose

intolerance in children who are at increased risk 

of developing type 2 diabetes later in life.
DMICC ANNUAL REPORT 56 FY 2003

National Institute of Dental and Craniofacial

Research (NIDCR) 

http://www.nidcr.nih.gov

The mission of NIDCR is to support research on the

causes, prevention, diagnosis, and treatment of oral

and craniofacial diseases and conditions. The oral

complications of diabetes include greater prevalence

and severity of periodontal diseases, increased 

susceptibility to oral mucosal infections, impaired

wound healing, salivary gland dysfunction, and neuropathies resulting in loss or alteration of taste,

smell, and mucosal sensory perception. The NIDCR

supports research on the oral complications of diabetes and the effects of oral diseases and conditions

on the metabolic control of blood glucose.

Current Activities

FY 2003 diabetes-related accomplishments include

the following:

• lA-2 and glutamic acid decarboxylase (GAD) are

major autoantigens in type 1 diabetes with

between 80 and 90 percent of newly diagnosed

type 1 patients showing autoantibodies to one or

the other of these autoantigens. Three separate

intramural collaborative clinical studies measured

these autoantibodies in patients with type 2 diabetes. Approximately 5 percent of type 2 diabetes

patients were found to have one of these autoantibodies. The investigators suggest that either these

subjects had been misdiagnosed and actually had

type 1 diabetes or that these patients’ disease

combined features of both type 1 and type 2 diabetes. Since there are over 16 million people in the

United States with type 2 diabetes, these findings

raise the possibility that an additional 1 million

persons may actually have type 1 diabetes or,

alternatively, that the numbers of persons with

diabetes involving autoimmunity may significantly exceed levels previously estimated.

• Oral inoculation of normal and diabetic NOD mice

with a periodontal diseases-causing bacterium

resulted in a failure of bone formation in diabetic

mice, resulting in a net loss of bone. More inflammatory genes were upregulated and a more 

prolonged inflammatory response occurred in 

diabetic mice as compared to normal mice.

• A pilot case-control study is determining the

extent of periodontal disease in Asian-Pacific

Islander (API) type 1, type 2, gestational diabetes,

or non-diabetic women who have term and preterm deliveries. Fetal cord blood is being analyzed

for markers of fetal exposure to oral pathogens of

maternal origin. Ultimately, the investigators will

seek to test the hypothesis that the prevalence of

periodontal diseases and levels of fetal exposure

to oral pathogens is higher for both diabetics and

non-diabetics whose pregnancies result in preterm deliveries vs. those delivering at term.

• Another clinical study in low-income AfricanAmerican and Hispanic children with type 1 or

type 2 diabetes aims to (1) identify their oral 

disease burden, (2) determine the relationship

between oral/periodontal changes and early signs

of other complications (retinopathy and nephropathy), (3) test an intervention to promote awareness

of the oral complications of diabetes mellitus

among medical staff providing care for children

and adolescents with diabetes, and (4) evaluate

the intervention’s impacts on early detection 

of oral diseases and utilization of oral health

services.
DMICC ANNUAL REPORT 57 FY 2003

• A pilot clinical trial on periodontal infection 

treatment and its effect on glycemic control will

complete patient followup in 2004. Estimates are

being obtained of changes in hemoglobin A1c and

the variability of those changes over time. Results

from this pilot project are expected to provide

preliminary data supporting the design of a Phase

III randomized clinical trial to evaluate the effect

of treating periodontal infection on glycemic control in type 2 diabetes.

Future Activities

During FY 2003 NIDCR continued to participate in

one Program Announcement (PA) "Enhancing

Adherence to Diabetes Self-Management Behaviors."

No additional initiatives are planned.

National Institute of Diabetes and Digestive 

and Kidney Diseases (NIDDK)

http://www.niddk.nih.gov

The National Institute of Diabetes and Digestive and

Kidney Diseases is the lead agency of the Federal

Government for research efforts to combat diabetes

and its complications. The Division of Diabetes,

Endocrinology, and Metabolic Diseases has responsibility for extramural programs related to diabetes

research and research training. The Division of

Intramural Research; the Division of Digestive

Diseases and Nutrition; and the Division of Kidney,

Urologic, and Hematologic Diseases support additional diabetes-related activities. In addition to the

diabetes research the NIDDK supports through its

regularly appropriated funds, the Institute also

leads and participates in a special U.S. Department

of Health and Human Services (DHHS) program 

on type 1 diabetes research, described below.

Special Statutory Funding Program for Type 1

Diabetes Research 

Section 330B of the Public Health Service Act 

provides the Secretary, DHHS, special funding for

research on the prevention and cure of type 1 diabetes. The Secretary has designated the NIDDK as

the lead organization for planning, implementing,

and evaluating this program. The special diabetes

programs were mandated for the period of FY 1998

through FY 2003 by the Balanced Budget Act of 

1997 (P.L. 105–33) and by the 2001 Consolidated

Appropriations Act (P.L. 106–554). The program was

extended for the period of FY 2004 through FY 2008

by the Public Health Service Act Amendment for

Diabetes (P.L. 107–360).

Under the leadership of the NIDDK, the Special

Statutory Funding Program for Type 1 Diabetes

Research has engaged in a broadly consultative

process that includes the participation of multiple

NIH Institutes and Centers, the Centers for Disease

Control and Prevention (CDC), and other DHHS components in all aspects of program planning, imple-
DMICC ANNUAL REPORT 58 FY 2003

mentation, and evaluation. In addition, the active

involvement of external scientific and lay experts

with respect to type 1 diabetes and the major 

diabetes voluntary organizations—the Juvenile Diabetes Research Foundation International and the

American Diabetes Association—has been vital to

the program's success in establishing a vigorous

and productive research enterprise.

The laws that established the special diabetes funding programs also mandate interim and final 

evaluation reports to the Congress. The interim

report on the special funding program for type 1

diabetes research was transmitted to the Congress

in June 2000. The enactment of P.L. 107–360 changed

the due date of the final program evaluation report

from January 1, 2003, to January 1, 2007. The NIDDK

has printed the evaluation report that was originally

intended to meet the January 2003, statutory reporting requirement. The document, entitled, “Special

Statutory Funding Program for Type 1 Diabetes

Research: Report on Progress and Opportunities,”

was issued as an important interim assessment of

the program by external scientific experts, grant

recipients, and NIH and CDC staff who analyzed the

associated scientific literature and other relevant

data on the program. Moreover, the report contains

a highly useful summary of research opportunities

identified by external experts in the field. These

opportunities can thus serve as a scientific guidepost in developing this trans-DHHS program in 

the years ahead.

The NIDDK has also launched a new website dedicated to the Special Program, which can be accessed

at: http://www.niddk.nih.gov/fund/diabetesspecialfunds/. Investigators can use this website to find

information on new and upcoming research funding

opportunities, the consortia and networks supported

by the program, special resources that are available,

and the recently published report.

Current Activities

The NIDDK supports a vigorous program of both

basic and clinical research to further understanding

of the development, treatment, prevention, and cure

of diabetes and its complications. To maximize

research on diabetes, the Institute has fostered collaborations among the many NIH Institutes and

Centers, as well as with the Centers for Disease

Control and Prevention (CDC), the Juvenile Diabetes

Research Foundation International (JDRF), and the

American Diabetes Association (ADA).

Capitalizing on and responding to recent advances

and emerging opportunities, the NIDDK continues 

to foster cutting-edge research in diabetes—from

the recognition and support for innovative ideas 

in investigator-initiated research, to the Instituteled establishment of consortia focused on important

fundamental and clinical research issues. Examples

of ongoing activities and new initiatives for 

FY 2003 follow.

Genetics of Type 1 Diabetes: Type 1 diabetes is an

“autoimmune disease,” in which the immune system

mistakenly attacks and destroys the beta cells of 

the pancreatic islets—the sole producers of insulin.

Without insulin, the body cannot properly regulate

glucose, lipid, and protein metabolism, which

results in physiologic alterations that can rapidly

cause death. Researchers have yet to determine the

precise factors that cause the immune system to 

initiate this misguided attack. However, many studies have suggested that an environmental exposure

may trigger this process in individuals who have an

underlying genetic susceptibility. Multiple genes 

are believed to be involved in an interplay with each

other and with the environment to initiate the cascade that leads to disease development. Identifying

genes that confer susceptibility or resistance to type

1 diabetes will propel the search for novel therapeutic targets and new assays to pinpoint those at risk

who can benefit from prevention strategies.
DMICC ANNUAL REPORT 59 FY 2003

International Type 1 Genetics Consortium.

Established by the NIDDK, in collaboration with 

the National Institute of Allergy and Infectious

Diseases (NIAID), the National Human Genome

Research Institute (NHGRI), and the JDRF, the consortium organizes international efforts to identify

genes that determine an individual’s risk of developing type 1 diabetes. Because large sample sizes are

required to identify susceptibility genes, the consortium will develop a renewable source of DNA on

7,500 families with a type 1 diabetic child. A consortium database containing clinical, genetic, and 

medical history information will facilitate the

search for susceptibility genes. The consortium 

also plans to develop a centralized DNA repository,

which will be accessible to genetic researchers in

the diabetes community.

Genetics of Type 2 Diabetes and Obesity: As with

type 1 diabetes, susceptibility to type 2 diabetes and

obesity is determined by both genetic and environmental factors. Environmental factors such as poor

diet and inactivity are risk factors, but less is

known about the genes involved. It is critically

important to identify genetic variations that predispose to type 2 diabetes and obesity, given the large

and increasing health burden they impose on the

American people.

International Type 2 Diabetes Genetic Linkage

Analysis Consortium. The NIDDK has sponsored 

this consortium to accelerate the search for type 2

diabetes susceptibility genes. The pooling of genetic

data from the many groups in the consortium

increases the probability of identifying genes that

influence this genetically complex disease. This 

combined effort also means that more samples are

available for analysis of individual ethnic groups

than is possible within a single study. Members of

this consortium are currently finishing genetic 

linkage studies.

Genetics of Obesity-Related Traits in Model

Organisms. The NIDDK, in collaboration with the

National Heart, Lung, and Blood Institute (NHLBI)

and the National Institute on Aging (NIA), is sponsoring an initiative to take advantage of the speed

and power of genetics in small model organisms—

such as fruit flies and zebrafish—in order to identify

obesity susceptibility genes. This information would

help to identify the corresponding genes in mice and

humans. This strategy might afford a quicker route

to identification of genes influencing these traits in

humans than attempts to identify such genes by

direct genetic analysis of mice or humans.

Genetics of the Complications of Diabetes: Genes

are a critical factor not only in the onset of type 1

and type 2 diabetes, but also in the onset and 

progression of the complications that result from

both forms of the disease. Familial clustering of

complications of diabetes suggests an important

genetic component to their development. Finding

susceptibility genes for complications has important implications for identifying and intervening in

individuals at increased risk for them, as well as 

for developing new therapeutic approaches. Several

initiatives aim to identify genes that predispose

individuals with diabetes to the development of

complications such as kidney and eye disease.

Epidemiology of Diabetes Interventions and

Complications (EDIC). The well-characterized 

participants in the Diabetes Control and Complications Trial (DCCT), and the follow-up Epidemiology

of Diabetes Interventions and Complications (EDIC)

study, provide an opportunity to elucidate the genetic factors that influence the risk of complications.

DNA and cell lines from over 1,400 DCCT/EDIC 

participants and their diabetic and non-diabetic 

relatives are being collected and analyzed to aid 

in the search for susceptibility genes for diabetes

complications.
DMICC ANNUAL REPORT 60 FY 2003

Family Investigation of Nephropathy and Diabetes

(FIND). Studies have shown that diabetic kidney 

disease is a highly heritable trait. In response to

this knowledge, the NIDDK established the FIND

study to uncover candidate genes associated with

development of kidney complications in patients

with type 1 or type 2 diabetes. FIND has also incorporated a retinopathy study. A specific objective is to

search for susceptibility genes in subpopulations of

Caucasians, African Americans, Hispanic Americans,

and Native Americans across the United States.

Three additional sites for recruitment of minority

participants have recently been added.

Animal Models of Diabetic Complications

Consortium (AMDCC). The NIDDK, in collaboration

with the National Eye Institute (NEI), the National

Institute of Dental and Craniofacial Research 

(NIDCR), NHLBI, and the JDRF, has expanded 

the “Mouse Models of Diabetic Complications

Consortium” to include other animal models.

Researchers in this consortium are developing animal models of diabetes complications to facilitate

the study of disease prevention and treatment and

the testing of candidate genes that emerge from

human genetic studies. The NIDDK, with the

National Institute of Environmental Health Sciences

(NIEHS), NHLBI, NEI, and the JDRF, recently sponsored a meeting, “Diabetic Complications: Progress

through Animal Models,” which emphasized the use

of animal models in discovery and translational

research. The meeting included presentations on

current and emerging animal models of diabetic

complications, molecular and cellular mechanisms

that lead to tissue damage, and the use of animal

models to understand complex trait genetics and 

to design clinical trials. Discussion sessions regarding areas of future scientific opportunity were 

also included.

Translational Research for Type 1 Diabetes and

Its Complications: It is critical to overcome barriers that prevent promising molecules and concepts

from moving from the bench, or laboratory, to the

bedside, where therapeutic agents can be tested for

efficacy in treating human disease. For example,

many academic scientists do not have the resources

necessary for the pre-clinical development of therapeutic agents. This can cause a promising agent to

be “stuck” in the laboratory, instead of moving forward for testing in human clinical trials. The Special

Statutory Funding Program for Type 1 Diabetes

Research has enabled the NIDDK to develop initiatives and resources to help investigators overcome

these types of barriers.

Type 1 Diabetes–Rapid Access to Intervention

Development (T1D–RAID). The NIDDK, in collaboration with the National Cancer Institute (NCI), has

launched the T1D–RAID program to foster development of new therapeutics for type 1 diabetes.

T1D–RAID is a special mechanism to make available

to academic investigators the necessary resources to

move novel molecules and concepts from bench-tobedside more rapidly and effectively. T1D–RAID 

will assist investigators by providing preclinical

development steps, the lack of which may be obstacles to clinical translation. Therapeutic agents that

can be developed through the T1D–RAID program

include small molecules, biologics, or vaccines for

the treatment or prevention of type 1 diabetes 

and its complications.

Bench-to-Bedside Research. The NIDDK has reissued

this initiative, which fosters interactions between

basic and clinical scientists to move discoveries

from a laboratory setting to preclinical or clinical

testing of new therapies that could improve the

health of individuals with type 1 diabetes.

Industry Participation. In collaboration with multiple other NIH Institutes, the NIDDK has sponsored 

a new Small Business Innovation Research (SBIR)

and Small Business Technology Transfer (STTR)

Request for Applications (RFA) on type 1 diabetes

and its complications. The purpose of this initiative

is to propel the small business community to use

cutting-edge technology in the research and development of commercial products, such as therapeutics, to prevent, treat, and cure type 1 diabetes and

its complications.
DMICC ANNUAL REPORT 61 FY 2003

Emerging Technologies To Study Type 1 Diabetes

and its Complications: The recent completion of

the Human Genome Project is a key example of how

an emerging technology—high-throughput DNA

sequencing—allowed researchers to achieve a

momentous accomplishment. Other new and innovative technologies are continually being developed.

Examples include technologies to describe the

dynamics of protein interactions (“proteomics”) and

technologies to study cellular metabolites, such as

lipids, amino acids, and carbohydrates (“metabolomics”). Proteomic technologies have been 

successfully used for studying several biological

processes relevant to human health. High throughput metabolic profiling has been recently implemented for metabolomic studies. However, these

technologies have only been applied in a limited way

to study type 1 diabetes and its complications.

Proteomics and Metabolomics in Type 1 Diabetes

and Its Complications. The NIDDK, in collaboration

with the NIAID, NEI, NHLBI, the National Institute

of Neurological Disorders and Stroke (NINDS), and

the National Institute of Child Health and Human

Development (NICHD), has sponsored an initiative 

to take advantage of new and innovative technologies to enhance understanding of type 1 diabetes

and its complications. These types of studies, which

can be performed at different times of disease development, could lead to invaluable information for

understanding the etiology and development of type

1 diabetes and its complications. Through this initiative, the NIDDK is promoting collaborative efforts

between investigators with expertise in proteomics

or metabolomics and investigators with expertise in

type 1 diabetes. These partnerships will encourage

type 1 diabetes investigators to expand their

research to include use of these technologies and

also provide proteomics investigators access to 

biological samples from type 1 diabetes patients or

animal models.

Beta Cell Biology and Cell Signaling: Beta cells 

of the pancreatic islets sense glucose levels in the

blood and respond by releasing insulin into the 

circulation when glucose levels exceed a physiologically-optimal range. Further understanding of cell

signaling in the beta cell has been a top priority

because altered function of this cell is central to the

pathogenesis of both type 1 and type 2 diabetes.

Beta Cell Biology Consortium (BCBC). The NIDDK has

bolstered research efforts through the BCBC, which

was created to facilitate interdisciplinary approaches to advance understanding of pancreatic islet

development and function. A new initiative, Seeding

Collaborative Research in Beta Cell Biology

(SCR–BCB), will promote collaboration among scientists working on areas such as development, systems biology, and pancreatic beta cells for the purpose of accelerating efforts towards the development of cell-based therapies for insulin delivery. A

related effort is the Endocrine Pancreas Consortium,

which works to apply the tools of functional

genomics to the endocrine pancreas, to identify the

genes expressed in mouse and human pancreas at

all stages of development, and to generate DNA

arrays and other tools to facilitate the identification

of important signaling components. The Consortium

has recently generated a research tool, called

PancChip 5.0, which contains over 14,000 mouse

genes that are important in the development of the

pancreas. This chip can be used by the diabetes

research community to study gene expression in the

pancreas, which may provide insights into diabetes.

Pilot-and-Feasibility Program in Human Islet Biology.

The importance of the need to obtain basic information about the general architecture and organization

of human islets was underscored at a recent NIDDKsponsored workshop, “Beta Cell Biology in the 21st

Century: Engineering a Pathway to Greater Understanding,” and also at an advisory meeting on islet

transplantation held in May 2003. In response to 

the challenges identified, the NIDDK has sponsored
DMICC ANNUAL REPORT 62 FY 2003

an initiative to increase understanding about the

structure, organization, and signaling properties 

of human islets. The information gained from these

studies should increase the ability to develop new

reagents for use in in vivo imaging studies of the

human islet, to develop assays for use in predicting

human islet transplant success, and to further

develop cellular therapies for potential use in the

treatment of type 1 diabetes.

Comprehensive Programs in Beta Cell Biology.

Pancreatic beta cells are in close contact with other

hormone-producing cells that collectively work to

regulate blood glucose levels. This initiative bolsters

investigator-initiated collaborative research focused

on signaling networks within the adult beta cell and

the integration of signaling networks within the

pancreatic islet. It seeks to characterize each step in

the molecular pathway by which glucose stimulates

insulin secretion, mechanisms by which other signals modify beta cell function, and the factors that

regulate beta cell growth.

Obesity—Critical in Diabetes and a Major Health

Problem of Its Own: The number of overweight and

obese Americans has risen dramatically in the past

two decades and is now at epidemic levels. Of 

particular concern is the increase in overweight in

children and adolescents. Obesity is a major risk

factor for numerous serious diseases, including type

2 diabetes, heart disease, and cancer. Overweight

and obesity disproportionately affect minority populations, particularly African-American, Hispanic,

and Native-American women and children. NIDDKsupported investigators are working to elucidate the

molecular factors that control appetite, metabolism,

and energy storage and are identifying potential 

targets for the development of new pharmacological

agents to promote safe, long-term weight loss. As

demonstrated recently by the landmark Diabetes

Prevention Program (DPP) clinical trial, a five-toseven percent sustained reduction in weight—

achieved through modest improvements in diet and

exercise—can delay or prevent the onset of type 2

diabetes in a high-risk population. Investigators 

are continuing behavioral research, such as that

employed in the DPP, to help people achieve lifestyle

modifications that include increased physical activity and improved diet.

The NIDDK Director has established an Office of

Obesity Research to encourage multidisciplinary

approaches to obesity and to coordinate all obesityrelated research within the Institute. The office will

coordinate the work of more than 11 programs with

major obesity-related components—ranging from

basic research to large clinical trials. The coDirectors of the Office of Obesity Research also lead

a Trans-NIDDK Obesity Research Working Group,

which synergizes efforts in this area across the

Institute. The NIDDK also supports Obesity/

Nutrition Research Centers and Clinical Nutrition

Research Units, which conduct both basicand 

clinical research studies.

The NIDDK Director and the NHLBI Acting Director

serve as co-chairs of the NIH Obesity Research Task

Force (ORTF), which was established in April 2003,

by the NIH Director to coordinate and facilitate obesity research efforts across the NIH. The ORTF

membership includes numerous NIH Institutes,

Centers, and Offices, as well as other NIDDK senior

scientific staff. The ORTF is developing a strategic

plan for obesity research, with external scientific

and public input, in order to address areas of 

scientific promise that can benefit from collaborative efforts.

Look AHEAD (Action for Health in Diabetes) Trial.

With support from other NIH Institutes and Centers,

the NIDDK has launched Look AHEAD—a multicenter clinical trial that will examine the health effects

of intentional weight loss in 5,000 obese diabetic

patients, with particular emphasis on cardiovascular health. Enrollment, begun in June 2001, is now

near completion. Trial participants, who will be followed for up to 11.5 years, are randomly assigned 

to one of two protocols, the Lifestyle Intervention,

which is designed to help participants achieve and

maintain weight loss over the long term, or Diabetes

Support and Education.
DMICC ANNUAL REPORT 63 FY 2003

Bariatric Surgery Clinical Research Consortium

(BSCRC). The NIDDK has established this

Consortium to facilitate research that would

enhance patient evaluation and selection and may

also lead to improved understanding of factors

underlying the development of obesity and its associated co-morbidities, with implications for new

strategies for prevention and treatment. The consortium also seeks to understand the risks and benefits

of bariatric surgery as a treatment modality.

Clinical Trials and Clinical Research: The NIDDK

has expanded clinical trials and clinical research

directed at advancing the prevention and care of

diabetes. Considerable work has been done to establish the clinical infrastructure essential for the efficient conduct of large, long-term trials by creating

national, multicenter research networks or consortia. Many of these consortia provide opportunities

for partnerships among the NIH, academia, and

industry for collaboration, co-funding, and support

of clinical research training in diabetes. This section

of the report describes major new results achieved

and new clinical research undertaken.

Cooperative Clinical Islet Transplantation

Consortium (CCITC). The NIDDK is currently creating

a major new islet transplantation network—the

Cooperative Clinical Islet Transplantation Consortium (CCITC). The purpose of the CCITC is to design

and implement human islet transplantation studies

that may eventually result in more effective treatment of type 1 diabetes. Some of the studies may

include: transplantation of islets alone, islets after

kidney transplantation, and simultaneous isletkidney transplantation; studies to better understand

islet engraftment or rejection; and new approaches

to minimize the toxicity of immunotherapy.

The Environmental Determinants of Diabetes in the

Young (TEDDY). An international consortium has

been established to provide a coordinated, multidisciplinary approach to understand the infectious

agents, dietary factors, or other environmental conditions that trigger type 1 diabetes in genetically

susceptible individuals. This information is crucial

for developing prevention strategies. In this longterm effort, high-risk infants will be identified at

birth and followed through adolescence. TEDDY is

supported by the NIDDK, in partnership with NIAID,

NICHD, NIEHS, CDC, JDRF, and ADA.

Type 1 Diabetes TrialNet. A consortium of investigators, clinical recruitment centers, and core support

facilities has been established to perform intervention studies to preserve pancreatic beta cell function in patients with new-onset type 1 diabetes and

to prevent type 1 diabetes in high-risk individuals.

TrialNet has recently completed the DPT-1 oral

insulin trial in individuals at intermediate risk for

developing type 1 diabetes. Researchers found no

difference in disease development between the study

participants who received oral insulin and those

who received placebo. TrialNet will also soon launch

a “Natural History Study of the Development of Type

1 Diabetes” for the screening of first-degree relatives

for the presence of autoantibodies; the assessment

of risk of diabetes based on number of antibodies

present, HLA type, and glucose intolerance; and the

assessment of the natural history of diabetes onset

in autoimmune pre-diabetes.

Continued Benefits of Improved Blood Sugar

Control. The landmark Diabetes Control and Complications Trial (DCCT) previously showed that intensive control of blood glucose levels reduced the 

risk of damage to small blood vessels and nerves 

in type 1 diabetes patients. The follow-up study,

the Epidemiology of Diabetes Interventions and

Complications (EDIC), continues to demonstrate

long-term benefits of intensive therapy in these

patients. In May 2002, EDIC investigators reported

that the 6.5 year period of intensive treatment 

during the DCCT continued to reduce the risk of 

eye disease as long as 7 years after the study ended.

Building on this exciting finding, a study in October

2003, showed that the former intensive treatment

group had a decreased incidence of both kidney
DMICC ANNUAL REPORT 64 FY 2003

damage and high blood pressure compared to the

former conventional treatment group 8 years after

the end of the DCCT. These long-term benefits were

observed despite nearly identical blood glucose control in the patients after completion of the DCCT.

While the DCCT proved that glucose control could

prevent small vessel damage, which causes kidney,

eye, and nerve problems, controversy remained

about the effect of high glucose levels on the large

vessels damaged in cardiovascular disease (CVD). In

June 2003, the DCCT/EDIC research group showed

that intensive control of blood glucose levels

decreased progression toward atherosclerosis in

type 1 diabetes. These results were achieved through

use of both ultrasound to measure thickening of the

wall of the carotid artery and also electron beam

computed tomography (EBCT) to measure coronary

calcification. This finding is significant because 

CVD causes death in two-thirds of patients with

diabetes.

The DCCT and EDIC studies have provided conclusive evidence that patients should begin intensive

therapy as early as safely possible. By maintaining

intensive therapy, patients have significantly

reduced development of diabetic complications,

including damage to both large and small blood vessels. Researchers will continue to investigate mechanisms by which glucose exerts its devastating

effects in the development of complications, with a

goal of discovering therapeutic targets for treatment

or prevention strategies.

Prevention of Type 2 Diabetes in People at High Risk.

The Diabetes Prevention Program (DPP) demonstrated that individuals at substantial risk of developing

type 2 diabetes could prevent or delay disease onset

and improve their blood sugar levels through modest improvements in diet and exercise. Minority

groups who are affected disproportionately from

type 2 diabetes—African Americans, Hispanic

Americans, Asian Americans and Pacific Islanders,

and Native Americans—made up 45 percent of the

over 3,200 individuals enrolled in the trial. The DPP

was the first major clinical trial to show that

improvements in diet and exercise can effectively

reduce diabetes in a diverse American population 

of overweight people with pre-diabetes. Results

from the DPP demonstrated a 58 percent decrease 

in the risk of developing diabetes with lifestyle

intervention, and a 31percent decrease in risk with

metformin treatment. The NIDDK is conducting follow-up studies of the DPP participants to determine

the durability of the DPP interventions in preventing

or delaying type 2 diabetes, as well as studying 

the long-term effect of the interventions on the

development of complications. This research will

also provide important information on the clinical

course of new-onset type 2 diabetes in this diverse

study population.

NIDDK Central Repositories. The NIDDK Central

Repositories were established for biosamples and

data collected in clinical studies. The purpose of the

Repositories is to expand the usefulness of these

studies by providing access to the biosamples and

data to a wider research community beyond the end

of a clinical study. The Repositories have three components: (1) Biosample Repository, which gathers,

stores, and distributes biological samples from

studies; (2) Genetics Repository, which receives and

processes blood samples to allow genetic analyses;

and (3) Database Repository, which gathers, stores,

and distributes the incremental or finished datasets

from studies. Samples and data from many diabetes

clinical trials will be deposited in the NIDDK

Central Repositories, which will be accessible to the

greater research community for additional studies.

Understanding Hypoglycemia in Type 1 Diabetes:

The potential for episodes of hypoglycemia, or low

blood sugar, has limited the use of intensive insulin

therapy that is known to reduce the risk of long-
DMICC ANNUAL REPORT 65 FY 2003

term diabetic complications. Normally, the brain

senses hypoglycemia and initiates a compensating

cascade of signals to elevate blood glucose levels.

However, in diabetic individuals who experience

repeated episodes of hypoglycemia, the brain fails 

to respond. Because of the importance of the brain

in this process, the NIDDK, in collaboration with

NINDS, is sponsoring an initiative to promote

research on how the brain and other critical tissues

sense and respond to hypoglycemia, understand the

effects of hypoglycemia on brain function, and

develop more effective methodologies to prevent

hypoglycemia.

Translating the Results of Clinical Research into

Clinical Practice: The dramatic, positive results 

of large clinical trials have given insights into

improved tools, treatment, and prevention strategies

for both type 1 and type 2 diabetes. A key challenge

is to ensure that the American people benefit from

these discoveries. One approach to this challenge is

to disseminate information, to those at risk and

their health care providers, about measures proven

effective for treating type 1 and type 2 diabetes and

for preventing type 2 diabetes in individuals at high

risk for this disease. It is also necessary to develop

methods to take interventions that have been

demonstrated to be beneficial in careful clinical

investigations and extend or adapt them to larger

populations or other settings. There is also increasing recognition that behavioral factors play a major

role in the increased prevalence of obesity and type

2 diabetes and in the management of diabetes and

its complications.

National Diabetes Education Program (NDEP). The

NDEP is a partnership among the NIDDK, the CDC,

and over 200 public and private organizations working together to reduce the morbidity and mortality

associated with diabetes. A key feature of this 

program is the participation of individuals who 

represent communities such as African Americans,

Hispanics/Latinos, Native Americans/Alaska

Natives, and Asian and Pacific Islanders who are

disproportionately affected by type 2 diabetes. The

NDEP’s “Small Steps, Big Rewards, Prevent Type 2

Diabetes” is a campaign to translate the positive

results of the DPP into real health improvements 

for the public. The educational material contains a

“Game Plan” that provides patients with information

about implementing a program to prevent or delay

disease onset. The NDEP's health awareness campaign, "Be Smart About Your Heart: Know the ABCs

of Diabetes,” is aimed at helping people with diabetes to better understand the need to control all

aspects of their diabetes to help prevent heart

attacks or strokes. The NDEP also has valuable

resources for children with diabetes and their caregivers. “Helping the Student with Diabetes Succeed,

A Guide for School Personnel” is a new comprehensive guide to empower school personnel, parents,

and students to ensure a safe learning environment

and promote a team approach to carry out a student’s diabetes care plan. The NIDDK plans to 

distribute this important Guide to all schools in the

country. The NDEP is also participating in the

“Diabetes Detection Initiative (DDI): Finding the

Undiagnosed,” which is an effort to identify individuals at high risk for undiagnosed type 2 

diabetes and then refer them for initial screening 

in a clinical setting and follow-up care, if needed.

The DDI is being piloted in 10 communities in a

variety of urban and rural settings, with future

plans for expansion.

National Kidney Disease Education Program

(NKDEP). This pilot program aims to prevent kidney

disease by raising awareness about the seriousness

of the problem and the importance of early diagnosis and appropriate treatment. The NKDEP is

designed to close the gap between scientific evidence and medical practice by educating physicians

and at-risk individuals, with the goal of identifying

kidney disease in its early, treatable stages. The

NKDEP pilot phase will initially target primary care

providers and people at highest risk for kidney dis-
DMICC ANNUAL REPORT 66 FY 2003

ease—particularly African Americans with diabetes,

high blood pressure, or a family history of kidney

disease—in four cities: Baltimore; Cleveland;

Jackson, Mississippi; and Atlanta.

Behavioral Research—Key to Prevention and

Treatment of Diabetes. Recent clinical trials have

provided definitive evidence that type 2 diabetes can

be prevented with lifestyle change and that rigorous

control of blood glucose, blood pressure, and lipid

levels can delay or prevent diabetes complications.

Yet, this control can be arduous—requiring adherence to a complex regimen of medications, diet, and

physical activity—therefore, very few Americans

with this disease can attain optimal control.

An initiative is intended to further research in

implementing the treatment and lifestyle changes

required to prevent diabetes in high-risk groups or

to improve outcomes in individuals with diabetes.

Clinical or behavioral studies are encouraged on

improving methods of health care delivery to

patients with or at risk of diabetes, improving 

methods of diabetes self management, and developing cost effective community-based strategies to

promote healthy lifestyles.

The NIDDK is also supporting research to study the

interactive nature of diabetes and co-occurring

depression. The NIDDK collaborated with the

National Institute of Mental Health (NIMH) and 

the NIH Office of Behavioral and Social Sciences

Research (OBSSR) in holding a major conference to

determine the state of knowledge with regard to the

co-morbid condition of depression and to propose a

research agenda for the future. Based on recommendations from this conference, an initiative was

developed to increase research activity on depression in relationship to diabetes, chronic renal disease, and obesity and eating disorders. As a result,

research efforts and interest in this field have

expanded significantly.

Advancing Research by Building Partnerships

and Attracting New Research Talent: Type 1 and

type 2 diabetes research spans an extraordinarily

broad range of scientific disciplines including

endocrinology and metabolism; immunology; cell

signaling; genetics and the influence of environmental factors; obesity; the physiology of the heart, eyes,

kidneys and urologic tract; and the central and

peripheral nervous system. In addition, research

efforts in these fields extend from basic laboratory

studies to clinical trials in human patients. Understanding the underlying biological mechanisms that

lead to onset of type 1 and type 2 diabetes, and

developing new strategies for prevention and cure,

will require a cadre of scientists with diverse

research training and experience. Furthermore, it is

important that scientists with diverse expertise collaborate—a multidisciplinary approach will propel

greater understanding of complex diseases.

Bringing Together Basic and Clinical Researchers. An

innovative “bench-to-bedside” program supports collaboration between basic research scientists, whose

findings have potential direct applicability to development of new treatments or diagnostic tests, and

clinical scientists, who can help translate these

basic discoveries into pre-clinical or clinical trials.

Attracting New Talent to Diabetes Research. An

innovative partnership program is promoting 

collaboration among diabetes researchers and 

those in areas other than diabetes who have expertise or technology that could advance diabetes

research projects. The goal is to encourage diabetes

researchers to act as “talent scouts” to identify other

researchers who could contribute to research breakthroughs in diabetes.
DMICC ANNUAL REPORT 67 FY 2003

Developing Clinical Researchers for Childhood

Diabetes. In collaboration with the ADA and the

JDRF, the NIH supports a program that fosters

development of a diverse and highly trained workforce of pediatric endocrinologists to assume leadership roles related to the Nation's biomedical and

behavioral research efforts in the area of pediatric

diabetes. This effort supports a combination of complementary programs at institutions with particular

strength in pediatric diabetes research. These combined programs will support development of new

researchers by providing research training during

pediatric endocrinology fellowships followed by a

special career development award framed to provide

research support for individuals who have completed their research training and have dedicated themselves to becoming independent clinical researchers.

National Institute of Environmental Health

Sciences (NIEHS)

http://www.niehs.nih.gov

Many environmental agents have been investigated

as contributing to the risk of diabetes. Environmental components have been suggested, especially

for type 1 diabetes, because concordance rates

between identical twins, where one twin has diabetes, remain at 30–50 percent. However, other environmental influences may also contribute to the 

rising incidence of type 2 diabetes as well.

The NIEHS is pursuing research in several areas 

relevant to environmental influences and diabetes,

as summarized below.

Current Activities

Recent studies have raised the possibility that certain chemicals in the environment, such as nitrates

in well water, increase the risks of type 1 diabetes.

Studies in the United Kingdom, Finland, and

Colorado indicate that the incidence of childhood

diabetes is higher in areas with elevated levels of

nitrate in the drinking water. This finding is significant for agricultural communities because well

water can have elevated nitrate levels in areas where

there is extensive use of fertilizers. Current and

future activities in this area by NIEHS intramural

scientists include:

• Initiation of a nested case-control study of environmental risk factors (e.g., pesticides, nitrates in

drinking water, animal contacts) for diabetes in

children of farmers enrolled in the Agricultural

Health Study, a prospective cohort study involving

nearly 60,000 licensed pesticide applicators and

32,000 spouses of applicators who are farmers.
DMICC ANNUAL REPORT 68 FY 2003

• Evaluation of diabetes risk along with other

health outcomes in the Agricultural Health Study.

Farmers are an otherwise healthy group whose

active lifestyle ought to decrease their risk for

type 2 diabetes. Against this background, the role

of potential environmental risk factors should be

easier to detect.

In other studies, intramural investigators at NIEHS

have reported an association between the body 

burden of a persistent organic pollutant (polychlorinated biphenyls) and type 1 diabetes. Current and

future studies in this area include:

• Further studies to examine the relation between

diabetes and body burden of persistent organic

pollutants are either underway or being planned.

For example, DNA is being collected from a cohort

of men so that polymorphisms in the Ah-receptor

(binds with dioxin-like polychlorinated biphenyls)

can be examined in relation to body burden of

persistent pollutants and risk of diabetes.

In extramural studies supported by the NIEHS,

investigators are studying the possibility that

arsenic in drinking water causes an increase in diabetes risk. Elevated levels of arsenicals in drinking

water are common throughout the world, and oxidative forms of arsenic are known to have cytotoxic

effects. These studies will:

• Investigate the effects of trivalent arsenicals 

and related compounds on glucose-stimulated

insulin secretion in pancreatic islets and cell 

culture systems.

• Examine the effects of these compounds on

insulin sensitivity in insulin-sensitive peripheral

tissues and in intact animals.

• Examine the possibility that arsenic is exerting

diabetogenic effects through direct interaction

with glucocorticoid receptors.

Other extramural research efforts are examining the

contributions of stress-activated protein kinases to

insulin resistance and type 2 diabetes, the mechanisms of action of xenobiotic beta-cell toxins in 

animal models, and a potential role for glutamatecysteine ligase gene polymorphisms in the pathogenesis of type 1 diabetes.

As noted above, the intermediate concordance rates

for type 1 diabetes have stimulated the search for

contributing environmental factors. Current and

future activities in this area by intramural investigators include:

• In collaboration with investigators in the United

Kingdom, the NIEHS is investigating the hypothesis that persistant materno-fetal michrochimerism

influences the development of type 1 diabetes in 

a set of monozygotic twins discordant for 

type 1 diabetes.

• The NIEHS is investigating the possibility of

establishing a discordant monozygotic twin registry in the United States for twins with type 1

diabetes, so that prospective studies of at-risk

twins can be carried out.

• The NIEHS is carrying out in-depth proteomic

evaluations of plasma and urine from patients

with diabetes in an attempt to identify novel 

protein markers of diabetes control and 

complications.

• Intramural investigators are carrying out studies

of risk factors for the development of polycystic

ovary syndrome in female twins. This common

syndrome of women of reproductive age is accompanied by insulin resistance, frequently leading to

diabetes, and this study hopes to develop novel

prevention strategies for this condition.
DMICC ANNUAL REPORT 69 FY 2003

Future Activities

Recent findings by intramural investigators using

knockout mice have identified the guanine

nucleotide regulatory or G protein G0 as an important regulator of glucose tolerance and glucosestimulated insulin secretion in mice. Future studies

will involve:

• Investigations into the molecular nature of the

enhanced glucose tolerance seen in the intact G0

knockout mice.

• Studies of the molecular mechanisms of the

enhanced glucose-stimulated insulin secretion

seen in isolated islets from the mice.

National Institute of General Medical Sciences

(NIGMS)

http://www.nigms.nih.gov

The National Institute of General Medical Sciences

supports research and research training in the basic

biomedical sciences that provide the foundation for

a better understanding of fundamental life processes. Some of this work has relevance to understanding

and treating diabetes.

Current Activities 

NIGMS supports the Human Genetic Cell Repository,

a collection of over 8,700 cell lines from individuals

with a wide variety of genetic disorders, including

diabetes, and from normal individuals. Cell lines in

the collection include those from individuals with

both type 1 and type 2 diabetes mellitus and its

complications. The repository includes an extensive

collection of cell lines from members of an extended

pedigree with maturity-onset diabetes of the young.

This collection is of value in studies designed to map

and characterize the gene(s) responsible for these

disorders.

DNA is also available for many of the cell lines in the

Human Genetic Cell Repository. In new initiatives,

the Repository has continued to collect new, large

panels of cell lines from individuals in ethnically

identified, minority populations within the United

States. These new collections supplement the panels

of cell lines from hundreds of unrelated individuals

that were acquired earlier, in order to facilitate

analyses of the genetic diversity of the U.S. population. This resource has proven to be of great value to

researchers for the discovery of DNA polymorphisms

important in pharmacogenetic studies and in the

identification of genes involved in complex genetic

disorders such as diabetes. The NIGMS Human

Genetic Cell Repository will continue to cooperate

with the National Human Genome Research Institute

in the collection of cell lines from around the world

for the HapMap project.
DMICC ANNUAL REPORT 70 FY 2003

NIGMS has an interest in understanding how genetic

and environmental components interact to result 

in complex diseases such as diabetes. The Institute

supports a portfolio of grants to develop better statistical methods for mapping and identifying genes

underlying complex traits, develop mathematical

models for studying gene-gene and gene-environment interactions, investigate DNA sequence 

variation and its evolution, examine gene activities

and the consequences of abnormalities in these

activities, and optimize sampling strategies. NIGMS

also supports pre- and postdoctoral training that

emphasizes statistical and computational skills and

workshops to provide additional training in statistical methods to biologists.

NIGMS support for research on the mechanisms

underlying individual variations in drug response,

while not specifically targeting diabetes, has the

potential to have an impact on the treatment of 

diabetes and its complications. Researchers are

studying the structural features of a powerful

peripheral vasodilator related to insulin identified 

as an important prospective drug for peripheral

angiopathies associated with diabetes.

NIGMS, in conjunction with several other Institutes,

is supporting a mouse mutagenesis and phenotyping

center whose emphasis is the high-throughput generation and identification of mice with mutations in

biochemical and developmental pathways that may

prove useful as models for human diseases.

NIGMS is also participating in the Trans-NIH

Zebrafish Initiative, whose goal is to improve the

genomic resources for the zebrafish, another potentially valuable model for diabetes studies.

NIGMS is now supporting a center to model 

metabolic systems in cells and tissues. A multicenter effort has also been funded to produce an

accounting of all of the types of lipids and lipidassociated proteins that are involved in every 

aspect of cell function.

NIGMS is sponsoring multiple research programs

that are seeking to understand the physiologic

processes involved in normal wound healing. While

this support has primarily been directed toward

efforts focused on trauma and burn injuries, there is

now an increasing interest in investigations of infectious, inflammatory, and metabolic factors that can

compromise wound repair in the context of chronic

conditions such as diabetes.

Future Activities

In the future, NIGMS will continue to support basic

research that focuses on underlying mechanisms 

and principles that are expected to shed light on

both normal and disease processes and to lead to 

the development of new modes of treatment and 

prevention.
DMICC ANNUAL REPORT 71 FY 2003

National Institute of Mental Health (NIMH)

http://www.nimh.nih.gov

The National Institute of Mental Health supports

research on the processes and mechanisms underlying co-morbid mental disorders and diabetes. It 

also supports research to develop and test preventive, treatment, and rehabilitative interventions 

for mental disorders in people with diabetes. The

interventions may be pharmacologic, behavioral,

or psychosocial.

Current Activities

In FY 2000–2001, NIMH and the National Institute 

of Diabetes and Digestive and Kidney Diseases cosponsored a major research conference, “Depression

and Mental Disorders in Patients With Diabetes,

Renal Disease, and Obesity/Eating Disorders,” on

January 29–30, 2001 at the Natcher Conference

Center, National Institutes of Health. The papers

resulting from the conference have been published 

in a 2002 special issue of the Journal of Psychosomatic Research (October 2002; 53(4)). The two

Institutes jointly released a Request for Applications

to fund new research projects in 2002. The NIMH

supported two applications with its available funds.

In addition, NIMH re-issued in 2002 its program

announcement calling for research applications 

on co-morbid mental and physical disorders, including diabetes.

National Institute of Neurological Disorders 

and Stroke (NINDS)

http://www.ninds.nih.gov

The National Institute of Neurological Disorders and

Stroke supports investigations of the neurological

complications of diabetes. Particularly important are

the neuropathies found in at least 60 percent of people with diabetes with symptoms such as pain,

numbness, double vision, and weakness at times to

the point of paralysis. Sensory impairment even

when sub-clinical, almost certainly contributes to

the development of foot ulcers in diabetics and these

may lead ultimately to amputations. The painful neuropathy/radiculopathy is very hard to manage and

may be mistaken for pain due to a herniated disc.

Symptoms of diabetic autonomic neuropathy can

include heart rate abnormalities, hypertension, dizziness, digestive disturbances, and impotence.

Autonomic neuropathy is an important cause of 

sudden cardiac death in people with diabetes. The

regulation by the central nervous system to maintain

euglycemia is also challenged by diabetes and

insulin therapy. Altered metabolism in the form of

low grade hypoglycemia (hypoglycemia unawareness)

may have long-term consequences in the nervous

system. Prevention and treatment of neurological

complications is a central therapeutic problem in

diabetes mellitus. Research supported by NINDS

spans these diverse areas.

Current Activities

NINDS has participated in nine initiatives related to

the special type 1 diabetes appropriations, three as

the lead institute. As the result of three Requests for

Applications (RFAs) published each year between FY

1998 and FY 2000, NINDS greatly expanded its

research into neurological complications of diabetes. These solicitations address early detection of

diabetic neuropathy, mechanisms of neuropathic

pain, the neurobiology of diabetic complications,

gene transfer for prevention of neuropathy, and

behavioral effects of both hypoglycemia and hyperglycemia.
DMICC ANNUAL REPORT 72 FY 2003

Several new NINDS applications were funded from

two FY 2002 RFAs. Applications in response to 

the RFA “Surrogate Endpoints for Diabetic

Microvascular Complications” are looking for ways

to detect early signs of diabetic neuropathy.

Applicants whose grants were in response to the

RFA “Effects of Hypoglycemia on Neuronal and Glial

Cell Function” are studying mechanisms by which

hypoglycemia effects astrocytes and neurons in the

central nervous system. In FY 2003, NINDS co-sponsored, with several other institutes, four new RFAs

aimed at diabetic complications.

NINDS continues to support a large epidemiological

study of neurological complications of diabetes in

the Rochester, Minnesota, area in the Caucasian and

Mdewakanton Dakota Native American and soon the

Hispanic populations. Diabetes is characterized by

large disparities in prevalence among ethnic groups,

but little is known about the extent of neurological

complications in these populations. This study will

be the first to document the extent and progression

of neurological complications in a longitudinal multiethnic cohort. Additional studies of this type have

been solicited in a new jointly issued Program

Announcement (PA), “Race/Ethnic Disparities in the

Incidence of Diabetes Complications.”

Future Activities

NINDS plans to continue investigations of diabetic

neuropathy and of hypoglycemia and may seek to 

re-issue PAs and RFAs pertaining to these topics.

National Institute of Nursing Research (NINR)

http://ninr.nih.gov/ninr

The mission of the National Institute of Nursing

Research is to support clinical and basic research to

establish a scientific basis for the care of individuals

across the lifespan—from management of patients

during illness and recovery to the reduction of risks

for disease and disability, the promotion of healthy

lifestyles, the improvement of quality of life in those

with chronic illness, and care for individuals at the

end of life. One purpose of this research, specific to

diabetes, is to understand how to promote healthsustaining behavior and to improve quality of life by

relieving the effects of disease processes and their

progression. Nursing research focuses on how physical and psychological responses to diabetes symptoms and treatment of the disease affect health

throughout the lifespan. NINR research programs

pay particular attention to the effect of diabetes in

minority and underserved populations.

Current Activities

In response to Program Announcements (PAs) or

Requests for Applications (RFAs) either directly or

indirectly related to diabetes research, NINR had 

an increase in diabetes funding in FY 2003.

In FY 2003 NINR continued to encourage diabetes

research through its participation in several ongoing PAs: Race/Ethnic Disparities in the Incidence of

Diabetes Complications (National Institute of

Diabetes and Digestive and Kidney Diseases

(NIDDK)); Translational Research for the Prevention

and Control of Diabetes (NIDDK); Enhancing

Adherence to Diabetes Self-Management Behaviors

(NINR); and Diabetes Self-Management in Minority

Populations (NINR). These PAs are consistent 

with Diabetes Research Working Group (DRWG) 

recommendations (NINR was a participant in this

working group).
DMICC ANNUAL REPORT 73 FY 2003

In response to increased congressional support for

type 1 diabetes research, NINR joined NIDDK to

sponsor two new RFAs issued in FY 2003: Small

Business Innovation Research (SBIR) and Small

Business Technology Transfer (STTR) to Develop New

Therapies for Type 1 Diabetes and its Complications;

and Innovative Partnerships in Type 1 Diabetes

Research.

NINR funded grants relating to diabetes research

included career development, postdoctoral training,

and investigator-initiated research. Diabetes-specific

topics include ethnic variations in type 2 diabetes

prevention knowledge, cardiovascular risk in adolescents with diabetes, Spanish language self-management programs, biobehavioral intervention studies

in African-American, Latino, and Korean-American

groups, an intervention for parents of young children with newly diagnosed diabetes, biophysical

determinants of diabetes foot ulcer healing, obesity

and diabetes prevention, diabetes self-management

using telehealth, and exercise and oxidative stress

in diabetes.

Future Activities

NINR plans to continue to support research that

focuses on problems experienced by those affected

by diabetes. Research efforts will be guided by the

following goals:

• FY 2004: NINR will work collaboratively with

other Institutes and organizations to increase and

facilitate diabetes research activities. NINR will

update and reissue productive Program

Announcements.

• FY 2005: NINR will focus support on promising

ongoing and new diabetes research opportunities,

while building on recent nursing science advances.

In summary, NINR activities are designed to support research related to interventions for persons

with diabetes, self-management, quality of life,

special and diverse population needs, problems of

defined age groups and across the lifespan, basic

research, genetics, and other initiatives relevant to

clinical practice and client outcomes. Translation of

science advances to the practice setting is ongoing.
DMICC ANNUAL REPORT 74 FY 2003

National Institute on Aging (NIA)

http://www.nia.nih.gov

The mission of the NIA as it relates to diabetes

research and related issues is to support biomedical

and behavioral research leading to improved therapies to prevent diabetes and its complications, as

well as to improve quality of life of older diabetic

patients.

Current Activities

An NIA-supported project has demonstrated a

cause-and-effect relationship between visceral fat

and major components of the metabolic syndrome.

Surgical removal of visceral fat in aging (20-monthold) F344/Brown Norway (FBN) and in Zucker

Diabetic Fatty (ZDF) (accounting for approximately

18 percent of their total body fat) was sufficient to

restore peripheral and hepatic insulin action to the

levels of young rats. While removal of visceral fat 

in ZDF rats prevented the progressive decrease in

insulin action and delayed the onset of diabetes, it

did not alter plasma free fatty acid levels. This data

suggest that insulin resistance and the development

of diabetes can be significantly reduced in aging

rats by preventing the age-dependent accumulation

of visceral fat.

The NIA Intramural Research Program has been

studying compounds that might be of use for treating type 2 diabetes. They have concentrated on compounds that induce insulin release (insulin release

is deficient in type 2 diabetes) and are protective of

the beta cell of the pancreas. A specific gut hormone, GLP-1, that is released after eating, can lower

blood sugar in type 2 diabetic subjects when given

in pharmacological doses. Exendin-4 is an agonist 

of the GLP-1 receptor. It has all of the benefits of

GLP-1 treatment and has the added advantage of

having a much longer half-life—about 2 hours.

Recently a study of subcutaneous exendin-4, given

twice daily to type 2 diabetic subjects, for 1 month

found: (1) exendin-4 is well tolerated, (2) that it

retains efficacy for at least 1 month, (3) there were

no unexpected side-effects, and (4) that it is at least

as effective in lowering blood glucose as current

treatments for type 2 diabetes. Thus, exendin-4

appears to be a viable potential candidate agent 

for treating type 2 diabetes and phase 3 studies to

evaluate efficacy and safety in a type 2 diabetic population are warranted.

NIA-supported research is also focused on ascertaining the effects of free fatty acids (FFA) on

endogenous glucose production (i.e., on gluconeogenesis (GNG) and glycogenolysis (GL)). Previous work

has established that FFA may mediate hepatic

insulin resistance (i.e., inhibition of insulin suppression of endogenous glucose production). Recent

results showed that insulin suppressed endogenous

glucose production primarily by inhibiting GL, and

elevated plasma FFA levels caused hepatic insulin

resistance by interfering with insulin suppression 

of GL. These observations may have pathophysiologic significance. In diabetic patients, partial unresponsiveness of endogenous glucose production to

hyperinsulinemia is a major problem contributing 

to hyperglycemia. These patients commonly have

elevated plasma FFA levels that may contribute to

this problem by inhibiting insulin-mediated suppression of GL.

Another NIA-funded study investigated the biochemical mechanism by which FFA cause insulin

resistance in skeletal muscle. This study examined

the possibility that FFA-induced insulin resistance

in human muscle is related to alterations in diacylglycerol (DAG)/protein kinase C (PKC) signaling. The

results suggest that the insulin resistance observed

in human muscle when plasma FFA levels were elevated was associated with large increases in DAG

mass and membrane associated PKC activity. The

data suggest that FFA cause insulin resistance by

DAG-mediated activation of PKC in muscle. Based on

other observations, it was suggested that FFA may

stimulate pro-inflammatory and pro-atherogenic

pathways. These new observations may help explain

some of the increased prevalence of coronary artery

disease in obese patients with type 2 diabetes,

because almost all of these patients have increased

plasma FFA levels and are insulin resistant.
DMICC ANNUAL REPORT 75 FY 2003

Caloric restriction (CR, i.e., limiting caloric intake

below ad libitum levels) in animal models, extends

maximum and average lifespan by as much as 40

percent and delays age-related pathologies. Among

the aging changes slowed by CR regimens are

declines in glucose tolerance and insulin sensitivity

and increases in body weight. To evaluate the effects

of CR interventions in humans, the NIA initiated the

group of U01 projects known as CALERIE

(Comprehensive Assessment of Long-Term Effects of

Reducing Intake of Energy). There are three clinical

sites, testing different interventions of CR in nonobese (but mostly overweight) individuals. Locations

of the clinical sites include the Washington

University in St. Louis, Tufts University in Boston,

and the Pennington Biomedical Research Center in

Baton Rouge. The Coordinating Center is located at

Duke Clinical Research Institute. The primary goals

of CALERIE are to gain knowledge: (1) about CR

effects in humans on physiology, metabolism, body

composition, and risk factors for age-related

pathologies, and (2) of similarities, differences and

interactions between the effects of CR and physical

activity on the physiological outcomes of interest

(e.g., changes in energy metabolism, surrogate markers of oxidative stress, endocrine function). Initiated

in early 2002, the CALERIE clinical sites are

presently conducting pilot projects of different CR

interventions involving 20–30 percent restriction of

energy intake. Some of the feasibility studies also

include physical activity interventions designed to

achieve similar levels of negative energy balance as

with CR. The results of these feasibility studies will

be subsequently used to design full-scale clinical

trial(s) of CR sustained for at least 2 years.

The NIA is a cosponsor of the National Institute of

Diabetes and Digestive and Kidney Diseases (NIDDK)

study, Diabetes Prevention Program-2 (DPP2).

The NIA is a cosponsor of the NIDDK Request for

Applications (RFA) (DK-03-022) “Ancillary Studies to

Obesity-Related Clinical Trials.” This initiative has

multiple receipt dates spanning FY 2004 and 2005.

National Institute on Alcohol Abuse 

and Alcoholism (NIAAA)

http://www.niaaa.nih.gov

The National Institute on Alcohol Abuse and

Alcoholism encourages research to understand the

role of alcohol consumption as a risk factor in the

development of obesity and diabetes mellitus. NIAAA

also supports research to determine the effects of

moderate alcohol consumption on diabetes. Several

studies suggest that alcohol consumption may

directly or indirectly contribute to the development

of type 1 diabetes based on the following observations: (a) alcohol impairs pancreatic insulin secretion; (b) chronic alcohol intake increases plasma TNF

levels which have been shown to cause pancreatic

beta cell apoptosis leading to decreased beta cell

number and insulin secretion; and (c) chronic alcohol

consumption may impair beta cell function by 

eliciting immunotoxicity.

Chronic alcohol consumption also has been implicated in the development of type 2 diabetes based on

the following findings: (a) chronic alcohol feeding in

rats reduces the number of insulin-binding sites on

isolated hepatocytes; (b) alcohol impairs insulinmediated tyrosine phosphorylation of insulin receptors in a tumor cell line; (c) chronic alcohol exposure

blunts tyrosine phosphorylation of insulin receptor

substrate-1 in rat hepatocytes and a tumor cell line;

and (d) chronic alcohol exposure inhibits the activity

of rat hepatocyte phosphotidylinositol-3kinase

which stimulates glucose transport. These effects of

alcohol may lead to insulin resistance and impaired

glucose transport.

Current Activities

Currently, NIAAA supports three projects that investigate the relationship between alcohol intake and

diabetes.The following research areas are under

investigation:
DMICC ANNUAL REPORT 76 FY 2003

• Impact of moderate alcohol consumption on the

risk of diabetes mellitus.

• Effects of fetal alcohol exposure on the biochemical and physiological changes in the insulin

response and glucose homeostasis.

• Molecular mechanisms of disruption of insulinmediated glucose transport by ethanol.

Future Activities

NIAAA will build up its portfolio on the interaction

between alcohol consumption and diabetes mellitus

and tissue injury. Activities planned include:

• Workshop. Role of Obesity in Alcoholic Liver

Disease: October 2003.

• Program Announcement. Alcohol, Obesity and

Diabetes Mellitus in FY 2004.

• Proposed Workshop. Alcohol and Diabetes in 

FY 2004.

National Institute on Deafness and Other

Communication Disorders (NIDCD)

http://www.nidcd.nih.gov 

Disorders of hearing, balance, smell, taste, voice,

speech, and language exact a significant economic,

social, and personal cost for many individuals. The

mission of the National Institute on Deafness and

Other Communication Disorders is to support and

conduct research and research training in the 

normal processes and the disorders of human communication that affect many millions of Americans.

NIDCD supports basic and clinical research on 

diabetes mellitus in the area of taste. Taste preferences for sweet-tasting substances play a crucial

role in the development of insulin and non-insulin

dependent diabetes.

Current Activities

NIDCD is supporting research on taste and endocrine factors in women with gestational diabetes.

Gestational Diabetes Mellitus (GDM) is a common

complication of pregnancy with serious consequences for maternal and child health. Diet is an

integral part of the management of GDM, but current

diet strategies for pregnant women with GDM are

poorly defined and often fail. NIDCD-supported 

scientists have observed that GDM increases the

preference for sweet taste and dietary intake of

sweet foods, which could have important implications for the management of this disease. At the 

time of diagnosis (approximately 30 weeks gestational age), pregnant women with GDM showed a

higher preference for sweetened dairy drinks compared to pregnant women without GDM. In addition,

increased plasma glucose in women with GDM was

related to higher preference for the sweet taste of

glucose and higher dietary intake of simple sugars

as fruit and fruit juices. Because these studies were

limited to a single observation point during gestation

and excluded women with severe diabetes or those

treated with insulin, further studies are needed.
The specific aims of this project are: (1) to determine

the relationship between hyperglycemia and increased taste preference and dietary intake of sweet foods

in GDM, (2) to compare the temporal pattern of taste

and dietary changes in women with GDM to those 

of women without GDM across pregnancy stages,

and (3) to relate these taste changes to alterations in

gestational hormone and metabolic profiles. A single

prospective study will be conducted to measure

sweet taste preferences, food cravings, dietary intake

of sweet foods, and plasma indices of selected hormones and metabolites (including insulin, cortisol,

and leptin) during early, middle, and late gestation

and at 6-week and 20-week post-delivery. The longterm goal of this project is to obtain a better understanding of taste changes in women with GDM to

develop better preventative and therapeutic dietary

intervention strategies for this disease.

National Institute on Drug Abuse (NIDA)

http://www.nida.nih.gov

A study on glucose metabolism disorders in HIVinfected drug abusers was funded by NIDA in FY

2003. A brief description of the study follows prepared by Andrea Howard, M.D., Montefiore Medical

Center, Bronx, New York.

Current Activities

Based on the fact that HIV-infected drug users may

be at heightened risk for impaired glucose tolerance

and type 2 diabetes mellitus in association with

protease inhibitor (PI) therapy and co-infection with

hepatitis C virus (HCV), the Principal Investigator is

funded to address these issues in a 5-year prospective study of 300 individuals with or at risk for HIV

infection in order to examine the associations of

HIV, PI therapy, and HCV infection with impaired

glucose tolerance and type 2 diabetes. The Principal

Investigator will: (1) determine the prevalence of

and factors associated with impaired glucose tolerance and type 2 diabetes in HIV-infected drug users,

including PI therapy, HCV infection, socio-demographics, body mass index, and family history of

diabetes; and (2) determine prospectively the impact

of HIV infection, PI therapy, and HCV infection on

the incidence of impaired glucose tolerance and type

2 diabetes. At semi-annual research visits, participants will undergo standardized interviews to

assess socio-demographics, medical history, and

drug use behavior; measurement of height, weight,

and waist/hip ratio; and blood tests for CD4+ count,

HIV viral load, HCV antibody, and HCV RNA level.

In addition, fasting lipid profiles and body composition analysis using dual x-ray absorptiometry will

be obtained. Oral glucose tolerance tests will be performed annually to screen for impaired glucose tolerance and diabetes. Active surveillance for clinical

DMICC ANNUAL REPORT 77 FY 2003
DMICC ANNUAL REPORT 78 FY 2003

disease events will also be performed. The Principal

Investigator’s long-term career goal is to become an

independent investigator of HIV epidemiology in

drug users. She will work closely with a multidisciplinary group of mentors with expertise in research

related to HIV, diabetes, hepatitis C, and substance

abuse and will also complete coursework in the conduct of diabetes-related clinical research, addiction

medicine, and the responsible conduct of research.

The proceedings of a workshop on “Interventions for

Metabolic and Endocrine Complications of

HIV/AIDS and Drug Abuse,” guest-edited by Jag

Khalsa, Sander Genser, and Henry Francis, of the

Center on AIDS and other Medical Consequences of

Drug Abuse, NIDA, was published as a special supplement in the Clinical Infectious Diseases journal

(September 1, 2003, volume 37(#2), pages s37–s153).

National Library of Medicine (NLM)

http://www.nlm.nih.gov

NLM explores the use of new information technologies to enable diabetes patients to manage their 

disease and avoid or delay the onset of costly and

debilitating complications, especially patients from

minority and medically underserved populations.

In particular, NLM seeks to learn how the use of

NLM’s MEDLINEplus website, and other computerbased health information resources, can be helpful

to patients, their families, and members of the public

to learn about and understand the latest research

news on diabetes, nutritional requirements, tests,

devices, and secondary prevention techniques and

for obtaining answers to patient-specific questions.

In the clinical setting, the principal hypothesis is

that MEDLINEplus can reinforce and supplement 

the information provided by physicians, nurses, and

health educators. A related hypothesis is that a 

combination of individualized training and access 

to publicly available computer resources at hospital

libraries and elsewhere in the community can help

bridge the “digital divide” experienced by minority

populations that have less ready access to computers

in the home, school, and workplace than the majority

population.

Current Activities

NLM develops, designs, implements, and evaluates 

a comprehensive program of diabetes-focused outreach initiatives in collaboration with academic

health science centers and libraries, clinical centers,

community-based organizations, and voluntary

health organizations.

Project A. Enhance the usability of MEDLINEplus for

Spanish-speaking users by developing a Spanish language version of the more than 500 health topics,

patient tutorials, medical encyclopedia, and drug

information database and evaluate its acceptance

among diabetes patients.
DMICC ANNUAL REPORT 79 FY 2003

Project B. In collaboration with two churches serving

the African-American community in Montgomery

County, Maryland, experiment with the concept of

“peer tutors” as a means to recruit teenagers at 

risk for type 2 diabetes, enhance their diabetes

knowledge with the use of MEDLINEplus, and

observe changes in risk behaviors by them and by

their peers.

Project C. In collaboration with the University of

Texas Health Science Center at San Antonio, and its

regional health center and clinics in the Lower Rio

Grande Valley, study how computer workstations

installed in clinic waiting rooms and in information

technology centers located in “colonias,” can provide

Hispanic patients with diabetes-related information.

Project D. In collaboration with Columbia University,

conduct field usability testing of IDEATel (informatics for Diabetes Education and Telemedicine) with

seniors and minority populations in New York City

and State. Study and evaluate the user interface and

the cognitive abilities of these patients to effectively

use the interface for remote in-home diabetes monitoring and education.

Veterans Health Administration (VHA),

Department of Veterans Affairs

http://www.va.gov/diabetes

The mission of the Department of Veterans Affairs

Healthcare System is to serve the needs of America's

veterans by providing primary care, specialized

care, and related medical and social support services. To accomplish this mission, VHA needs to be a

comprehensive, integrated healthcare system that

provides excellence in healthcare value, excellence

in service as defined by its customers, and excellence in education and research, and it needs to be

an organization characterized by exceptional

accountability and by being an employer of choice.

The mission of the VHA diabetes program is to

improve the health of veterans with diabetes by

decreasing the incidence of adverse health outcomes, especially macrovascular and microvascular

disease. This will be accomplished through systemslevel integration of guidelines, performance measurement, data feedback, and education to promote

the increased use of evidence-based preventive and

treatment processes. VHA research service supports

this mission through clinical, basic science, and

health services research. VHA reports the following

progress in FY 2003.

Current Activities

Performance Measurement (Office of Quality and

Performance). In FY 2003,VHA, through its ongoing

External Peer Review Program, collected data from a

random sample of veterans with diabetes from each

VHA facility. A patient must have accessed VHA for

any type of care some time at least once 2 years ago

and at least once during the previous 12 months.

The percentage of patients having chart documentation of the following measures, and the increase

from FY 2002, is as follows: 
DMICC ANNUAL REPORT 80 FY 2003

• HbA1c test (94%); 81percent of HbA1c values less

than 9 percent (+3%); lipid profile within 2 years

(94 percent; 71 percent of LDL-C values less 120

mg/dl (+8%); Blood pressure control, 71 percent

less than 140/90 (+13%).

• Dilated retinal examination, 75 percent (+3%).

• VHA adherence to diabetes and non-diabetes indicators exceeded the average in Medicare Fee for

Service in FY 2000 on 12 of 13 common indicators

(Effect of the Transformation of the Veterans

Affairs Health Care System on the Quality of Care,

N Engl J Med, 348: 2218-2227, 2003).

Lower Extremity Amputation Programs (Offices of

Patient Care Services and Medical Inspector). In 

FY 2001 the Under Secretary for Health reissued the

VHA Preservation, Amputation Care and Treatment

Directive (PACT), which mandates multidisciplinary

foot care programs, including screening, surveillance, and salvage components, at all VHA facilities.

Over 92 percent of veterans have an annual visual

foot examination, and about 84 percent have a 

sensory examination. From FY 1999–FY 2002, the

age-adjusted rate of total diabetes-related amputations decreased performed in the VHA has decreased

from 7.68 per 1,000 veteran clinical users to 4.84.

Major amputations decreased from 3.9 per 1,000

veteran clinical users to 2.3, and minor amputations

decreased from 3.78 per 1,000 veteran clinical users

to 2.54.

Guideline Development (Offices of Quality and

Performance and Patient Care Services ). VHA, in

partnership with the Department of Defense, updated its Diabetes Clinical Practice Guidelines (May

2003). The guidelines, covering outpatient management of glycemia, blood pressure, hyperlipidemia,

diabetic retinopathy, foot care, and renal disease,

emphasize transparency of the evidence underlying

clinical recommendations as well as principles 

of absolute risk reduction and patient-clinician

decision-making.

Research Service. There are three VHA Research

Enhancement Award Programs (REAPs) on diabetes

research funded by Medical Research Service. The

REAPs focus on investigating the effects of diabetes

upon the vascular system; the regulation of gene

transcription by insulin and by glucose and its

metabolites in order to improve insulin responsiveness; and the mechanism linking decreased islet

beta-cell function to the abnormal glucagon secretion that occurs during hypoglycemia in patients

with diabetes.

Ongoing programs include the 5-year cooperative

study (VA Diabetes Trial, CSP #465) to evaluate the

effect of near-normal glycemic control upon cardiovascular outcomes in type 2 diabetes.

The VHA Quality Enhancement Research Initiative

(QUERI) has been cited by the Institute of Medicine

as a model for translational research. Diabetes

Mellitus-QUERI program continues to focus upon

more aggressive treatment of modifiable risk factors

and the prevention of progressive complications

among veterans with diabetes and continues to

work with partners outside VHA, including the

Centers for Disease Control and Prevention

(Translating Research Into Action for Diabetes).
DMICC ANNUAL REPORT 81 FY 2003

Education. Over thirty VHA facilities have obtained

American Diabetes Association Recognition of their

patient education programs—more than any other

national system of health care. VHA hosted the

annual VA Diabetes Educators Conference for over

200 VHA clinician educators. This represents an

institutional commitment to translating agency priorities and research findings into results at the field

level.

Future Activities

VHA remains committed to leveraging performance

measurement, its medical informatics system,

research, and patient and clinician education to

improve interim metabolic outcomes (A1c, blood

pressure, and cholesterol), as well as to improve cardiovascular, chronic kidney disease, eye, and foot

care outcomes.
THE NATIONAL DIABETES EDUCATION PROGRAM
DMICC ANNUAL REPORT 85 FY 2003

http://www.ndep.nih.gov

Fiscal Year 2003 Accomplishments

The National Diabetes Education Program (NDEP) 

is sponsored by the National Institute of Diabetes

and Digestive and Kidney Diseases (NIDDK) of the

National Institutes of Health and the Centers for

Disease Control and Prevention (CDC) and is a 

subcommittee of the Federal Government’s Diabetes

Mellitus Interagency Coordinating Committee

(DMICC). The program develops information and

education messages and materials for people with

diabetes and their families, health care providers,

payers and purchasers of health care, health care

system policymakers, and the general public, including people with undiagnosed diabetes and those at

risk for the disease.

The NDEP’s efforts are aided by a Steering

Committee comprised of representatives from 

diabetes-related, health care, racial/ethnic, and 

voluntary service organizations. Federal liaisons to

the NDEP Steering Committee include several representatives from the DMICC. Members of the Steering

Committee serve on NDEP work groups that provide

direction and help implement NDEP initiatives.

The NDEP also has developed a Partnership

Network of over 200 organizations to help disseminate program messages to the mass media,

community groups, and health systems serving 

people with diabetes. The website, “Team Diabetes,”

provides an interactive, online site for NDEP 

partners to exchange resources and information.

Fiscal Year 2003 Highlights

During FY 2003, NDEP supported a variety of activities to promote the importance of comprehensive

diabetes care and diabetes prevention. Highlights 

of NDEP’s activities during the past year are 

summarized below.

Media Campaigns

From June 1998, when NDEP launched its first

Public Service Advertisements (PSA) campaign,

through September 30, 2003, the NDEP’s diabetes

control and prevention television PSAs have

obtained well over $17 million in free advertising

time, and print PSAs have reached over 36 million

readers. NDEP carried out extensive market research

before initiating its PSA campaigns and has developed the messages in conjunction with NDEP work

groups. The program also has provided ongoing 

support for continuing campaigns targeted to

African Americans, Hispanic and Latino Americans,

American Indians and Alaska Natives, and Asian

Americans and Pacific Islanders.

The “Small Steps. Big Rewards. Prevent Type 2

Diabetes” campaign is based on the results of the

Diabetes Prevention Program (DPP) clinical trial that

proved diabetes could be prevented or delayed in an

overweight population with pre-diabetes. The “Small

Steps” campaign encourages people at high risk to

lose a small amount of weight by eating healthy and

getting 150 minutes of physical activity a week.

In November 2002, HHS Secretary Tommy G.

Thompson launched the “Small Steps” campaign 

and the “Get Real” TV PSA. To date, “Get Real” TV

PSAs have generated nearly $1.5 million in free

advertising, and the print PSAs have reached 

almost 1 million readers.

In February 2003, the NDEP held the first national

“Partners in Diabetes Prevention” meeting to encourage NDEP partners, businesses, and communitybased programs to promote NDEP’s diabetes 

prevention messages and materials. NDEP unveiled

and distributed the “Small Steps GAME PLAN”

toolkit at this meeting. The toolkit contains information and education materials for health care

providers to help their patients take steps to lower

THE NATIONAL DIABETES EDUCATION PROGRAM
DMICC ANNUAL REPORT 86 FY 2003

their risk for diabetes. In less than 6 months, 3,000

GAME PLAN toolkits and 3,000 packets for patients

have been distributed.

The “Be Smart About Your Heart: Control the ABCs 

of Diabetes” campaign creates awareness about the

link between diabetes and heart disease and promotes comprehensive diabetes care to control blood

glucose (A1c), blood pressure, and cholesterol—the

ABCs of diabetes.

In November 2002, the NDEP continued partnering

with the American Diabetes Association (ADA) to

promote the ABCs message by distributing the ADA’s

“Broken Heart” campaign materials, including print

and radio PSAs with the NDEP logo, to over 200

NDEP partners.

The NDEP has adapted the “Control the ABCs”

message into Spanish for reaching Hispanic and

Latino Americans and created the “Si Tiene Diabetes,

Cuide su Corazon” (If you have diabetes, take care 

of your heart) campaign. To reinforce the campaign

message, NDEP developed a bilingual flipchart for

health educators to explain the link between diabetes and heart disease, using easy-to-understand

illustrations accompanied by a scripted presentation

and copier-ready handouts (in Spanish and English).

Also in FY 2003, the “Take Care of Your Heart.

Manage Your Diabetes” educational handout was

adapted into 15 Asian and Pacific Islander languages. The handout explains the link between diabetes and heart disease and the importance of managing blood glucose, blood pressure, and cholesterol

and is available in English and the following languages: Cambodian, Chamorro, Chinese, Chuukese,

Gugarati, Hindi, Hmong, Japanese, Korean, Laotian,

Samoan, Tagalog, Thai, Tongan, and Vietnamese.

Media Outreach

In conjunction with these awareness campaigns,

NDEP continued to conduct media outreach to

obtain coverage about diabetes in the print and

broadcast media. Program messages were featured

in a number of national media outlets, including The

New York Times, Time, Newsweek, Ladies Home

Journal, Essence, Prevention, and Woman’s Day,

and generated almost 64 million media impressions.

NDEP Conference Participation

Program spokespersons gave presentations and 

represented NDEP at numerous professional 

meetings in FY 2003, including the American Public

Health Association (APHA) (November 2002); the

CDC’s Diabetes Translation Conference (May 2003);

American Diabetes Association and National

Association of School Nurses (June 2003); National

Association of La Raza (July 2003); and Administration on Aging and the Food Marketing Institute

(September 2003).

Diabetes at the Worksite

NDEP’s Business and Managed Care Work Group 

has designed a web-based resource that employers,

human resource, and health professionals can use 

to assess the scope of the diabetes problem in their

workforces and to conduct diabetes education at 

the worksite. Hosted by the Washington Business 

Group on Health, this resource is available at 

www.diabetesatwork.org. In November 2002,

during the APHA meeting in Philadelphia, NDEP conducted a workshop for local businesses on how to

use the resources on this website. NDEP is planning

to conduct additional workshops during FY 2004.

Diabetes in Children and Adolescents

In June 2003, the NDEP launched Helping the

Student with Diabetes Succeed: A Guide for School

Personnel. This manual helps school personnel

ensure a safe learning environment for children 

with diabetes and equal access to all educational

opportunities. Also released in FY 2003 are four tip

sheets for children with type 2 diabetes and their

families. Topics covered include: what is diabetes,

staying at a healthy weight, eating healthy, and

being more physically active.
DMICC ANNUAL REPORT 87 FY 2003

Systems Changes for Better Diabetes Care

NDEP’s Health Care Provider work group provided

guidance for BetterDiabetesCare.nih.gov, a new 

website. This practical resource is designed to help

health care providers make a difference in the way

diabetes is prevented and treated. The work group

undertook this task to help address the steps outlined by the Committee on the Quality of Health

Care in America in its 2001 report to the Institute 

of Medicine. The NDEP believes that systems change

is essential to provide the type of evidence-based,

patient-centered care needed to manage diabetes

effectively and to prevent its serious complications.

The website provides models, links, resources, and

tools to help the professional assess needs, plan

strategies, implement actions, and evaluate results.

The Pharmacy, Podiatry, Optometry, and Dentistry

(PPOD) work group is finalizing a diabetes primer to

expand PPOD professionals’ understanding of their

role in caring for people with diabetes beyond their

own specialty and to include education about the

need for glycemic, blood pressure, and cholesterol

control for people with diabetes. A poster aimed at

people with diabetes is being developed based on

the principles outlined in the primer.

The Older Adults work group is finalizing materials

to promote the Medical Nutrition Therapy and diabetes self-management benefits for people with 

diabetes who are enrolled in Medicare.

Future Activities

During FY 2004, NDEP will continue to promote

comprehensive diabetes control and diabetes prevention. The NDEP is tailoring the messages and

materials from the “Small Steps” prevention campaign for high-risk population groups, including

older adults, African Americans, Hispanic and Latino

Americans, American Indians and Alaska Natives,

and Asian Americans and Pacific Islanders.

The program also will promote the U.S. Department

of Health and Human Service’s “Diabetes Detection

Initiative,” designed to reach people with diabetes

who are undiagnosed. A component of “Steps to a

HealthierUS,” this initiative focuses on helping

Americans better understand their diabetes risks

and what actions they need to take.

These new and important NDEP prevention and 

control messages and initiatives will add a new

dimension to the NDEP and its goal of “changing 

the way diabetes is treated.” For more information

about the National Diabetes Education Program,

please visit our websites at www.ndep.nih.gov 

and www.cdc.gov/team-ndep on the Internet.
MEETING SUMMARIES
DMICC ANNUAL REPORT 91 FY 2003

DIABETES MELLITUS INTERAGENCY

COORDINATING COMMITTEE MEETING

National Institutes of Health Campus

Natcher Conference Center, Conference Room A

Bethesda, Maryland

February 25, 2003

THE METABOLIC SYNDROME

SUMMARY MINUTES

Dr. Saul Malozowski, Executive Director of the

Diabetes Mellitus Interagency Coordinating

Committee (DMICC), convened the meeting and presented Dr. Allen Spiegel, DMICC Chair and Director,

National Institute of Diabetes and Digestive and

Kidney Diseases (NIDDK), National Institutes of

Health (NIH). Dr. Spiegel welcomed the speakers,

committee members, and guests. He stated that 

they were an important body of persons with the

opportunity to coordinate manifold activities as 

representatives of agencies of the U.S. Department 

of Health and Human Services (DHHS), along with

important stakeholders such as the American

Diabetes Association (ADA) and the American

Association of Clinical Endocrinologists (AACE).

Dr. Spiegel noted that there are critical issues to be

addressed regarding the metabolic syndrome. These

include definition issues, the etiology of the metabolic syndrome, risk factors represented by the 

syndrome, and implications for prevention and

treatment of the syndrome. Since a major definition

was developed by the National Heart, Blood and

Lung Institute’s (NHLBI’s) National Cholesterol

Education Program’s (NCEP’s) Adult Treatment Panel

III (ATP III), the group was fortunate to have Dr.

Peter Savage present today representing NHLBI’s

membership on the DMICC. Dr. Claude Lenfant,

NHLBI Director, regretted not being able to attend

but was looking forward to hearing the results of

the meeting.

Dr. Savage, Director, NHLBI Division of Epidemiology

and Clinical Applications, joined Dr. Spiegel in

emphasizing that today’s meeting provided the

group with a major opportunity to discuss the metabolic syndrome and its relationship to diabetes 

and to cardiovascular complications in non-diabetes. He agreed that there were many questions 

to be answered regarding the definitions and the

magnitude of the problem. An overview of these

issues would be presented by three speakers very

active in the field—Dr. James Meigs, Dr. Steven

Haffner, and Dr. Scott Grundy. Following these

overviews, DMICC agency representatives and members of ADA and AACE would present their groups’

perspective on the metabolic syndrome. (Dr.

Haffner’s and Dr. Grundy’s slide presentations are

available at http://www.niddk.nih.gov/federal/

dmicc/Haffner.ppt and http://www.niddk.nih.gov/

federal/dmicc/grundy.ppt. For informational purposes and due to the need of further analyses only part

of these presentations are available. (Dr. Meigs

slides could not be posted because they contained

data that has not been published yet.)

James B. Meigs, MD, MPH, Assistant Professor of

Medicine, General Medicine Division, Harvard

Medical School, and Massachusetts General 

Hospital, Boston.

Definitions of the Metabolic Syndrome and

Related Risk of Heart Disease and Type 2

Diabetes

Dr. Meigs introduced the NCEP ATP III definition,

developed in 2001, and the World Health

Organization (WHO) definition of 1999 (see box),

which differ in trait thresholds and inclusion criteMEETING SUMMARIES
DMICC ANNUAL REPORT 92 FY 2003

ria. Regardless of the definition

used, the metabolic syndrome is

very common, according to Dr.

Meigs. Those with the syndrome,

again regardless of the definition, are more insulin resistant

and at greater predicted risk for 

coronary heart disease (CHD)

and diabetes. Presence of the

metabolic syndrome doubles 

the risk for CHD events and 

dramatically increases by as

much as 10-fold the risk for type

2 diabetes. Specific clustering of

traits may better predict the risk

or burden of CHD or type 2 

diabetes than the presence of

any three individual traits.

According to data from the

Framingham Heart Study, in which Dr. Meigs has

been a key participant, prevalence of the NCEPdefined metabolic syndrome increased from about

15-20 percent in men and 7-16 percent in women

from the late 1980s to the mid-1990s.

Prevalence by Definition. Based on the National

Health and Nutrition Examination Survey of 1999-

2000 (NHANES III), the metabolic syndrome as

defined by NCEP tends to be heterogeneous across

racial/ethnic populations, is more common in men

than in women, and prevalence increases with age.

Population-based comparisons of the data from

NHANES III, the San Antonio Heart Study, and the

Framingham Offspring Study indicate that, of the

components of the NCEP definition, hyperglycemia

was the least common trait. Components varied

across populations and tended to be most prevalent

in Mexican Americans. It was interesting that both

whites and Mexican Americans had a higher prevalence of the syndrome than white Finnish males in

the Kuopio IHDRF Study, possibly because the

Kuopio men are relatively slender. Comparing the

prevalence of the WHO metabolic syndrome traits 

in populations from the Framingham Offspring

Study, the San Antonio Heart Study, the Botnia Study,

and the Kuopio IHDRF Study, hyperglycemia with or

without insulin resistance (IR) was nearly as common in white Finns from Botnia as it was in the San

Antonio Mexican Americans as was the prevalence 

of the syndrome, with 46 percent of the Botnia 

subjects and 49 percent of the Mexican Americans

having the syndrome.

Issues in Defining the Syndrome. Dr. Meigs listed

several uncertainties that arise in considering any

definition of the metabolic syndrome. Should simple

trait counting be used or empiric weights or 

clusters? Are insulin levels being measured or

insulin resistance? Should high glucose or diagnosed

diabetes be included as part of the definition or as

an outcome? Which is a better indicator, BMI or

waist circumference? What about microalbuminuria

or C-reactive protein (CRP) and other inflammatory

markers? Finally, which thresholds should be used—

NCEP or WHO? Comparison of waist circumference

versus waist:hip ratio is not the same measure 

and NCEP does not include BMI, fasting glucose,

or diabetes.

In counting traits, rather than clusters, Dr. Meigs

said it is important to note that the individual 

syndrome traits do not have equal predictive power.

On the other hand, factor analyses show that certain
DMICC ANNUAL REPORT 93 FY 2003

traits tend to cluster, suggesting physiological trait

clusters exist, and that the most common clusters

include from two to four factors. This may indicate 

a need to define the syndrome by requiring selection

of traits based on their specificity for insulin resistance. For instance, requiring that a large waist 

circumference and low HDL/high triglyceride dyslipidemia be present may increase the specificity of

the diagnosis of metabolic syndrome. Comparisons

were made of Framingham Offspring and San

Antonio Heart Study subjects with factors added,

such as BMI and empiric clusters to the NCEP and

microabluminuria to WHO. Dr. Meigs pointed out

that overall prevalence and the degree of HOMA-IR

(homeostasis model assessment of IR) between

whites and Mexican Americans is highly similar

regardless of the alternative definition used, except

for slightly higher rates according to the WHO definition, especially for Mexican Americans. Also, the

prevalence drops dramatically when the NCEP 

definition is applied with empiric clusters, although

subjects remain quite insulin resistant and at 

elevated predicted CHD risk even by this definition.

Metabolic Syndrome and Risk for CHD and

Diabetes. The risk for coronary heart disease (CHD)

based on the Framingham Heart Study Risk Score 

is also similar, regardless of alternative definitions

used, with both whites and Mexican Americans who

have the metabolic syndrome being at much higher

risk. The 11-year adjusted relative risk for CHD and

all-cause mortality associated with the metabolic

syndrome, regardless of definition, was also true for

Finnish men in the Kuopio IHDRF Study. The relative

risk for CHD and cardiovascular disease (CVD) in the

Framingham Offspring Study participants showed

slight differences between those who had two versus

three traits of the metabolic syndrome, but with

three traits certainly increasing the risk. Dr. Meigs

emphasized that, on the other hand, the presence of

any two or three traits was a powerful indicator of

risk for diabetes.

Dr. Meigs next described the population-attributable

risk percent (PAR%) formula, or the burden of 

disease that can be attributed to a given condition,

as a clinically useful indicator for public health. He

stated that, in the Framingham Offspring Study, the

8-year age-adjusted relative risk and PAR% for CHD

was always highest for those with a three-way 

combination that included lipid and waist traits.

For type 2 diabetes. the PAR% was very high for any

three-way combinations, with those including 

fasting glucose and waist traits being the highest 

for both relative risk and PAR%.

The risk of CHD was higher in those with the 

fasting plasma glucose and waist combination and

increased in those who had any three-way combination, any two-way combination, or the HDL-blood

pressure combination. The burden of CHD increased

as persons had any two-way combination of traits

and increased with any three-way combination or

HDL-blood pressure combination.

For diabetes, the risk increased beginning with the

fasting plasma glucose trait in combination with

any other one or two traits and the risk increased 

or was equal to this with any two- or three-way

combination of traits. The public health burden for

diabetes was predictable given any three-way or

two-way combination of traits and increased with

the presence of the HDL-waist combination.

Steven M. Haffner, MD, MPH, Professor of Medicine,

Department of Medicine/Clinical Epidemiology,

University of Texas Health Science Center,

San Antonio.

Etiology(ies) of the Metabolic Syndrome and

Variations Across Racial/Ethnic Groups

Dr. Haffner presented the risk of CHD and/or of 

diabetes as one criteria for comparing the NCEP 

and WHO definitions of the metabolic syndrome. A

second possible criteria is the relation of the syndrome to IR, and a third is the prevalence of the 

syndrome in the community and by different

racial/ethnic groups. The metabolic syndrome is

associated with increased risk of heart disease,

although the increased risk may not be entirely due

to increased IR. On the other hand, most subjects
DMICC ANNUAL REPORT 94 FY 2003

with the metabolic syndrome do not have type 2 

diabetes. African Americans tend to have low triglycerides and high HDL; therefore, the prevalence of 

the metabolic syndrome in this population is lower

according to the NCEP definition and is higher

according to the WHO definition, a peculiarity that

Dr. Haffner felt deserves consideration. He stated

that another thing to consider is the simplicity or

understandability of the definition in order to apply

it in the general population not just discuss it as a

theoretical aspect.

Dr. Haffner addressed the prediabetic state as a

model for the metabolic syndrome; insulin resistance, insulin secretion, and subclinical inflammation

as predictors of the metabolic syndrome; the relation of inflammation to increased insulin resistance

and decreased insulin secretion; factor analyses

from the Framingham and the Insulin Resistance

Atheroscerlosis Study (IRAS); the metabolic syndrome, diabetes, and coronary heart disease 

prevalence in the NHANES and other database 

populations; and identification of persons with

insulin resistance and beta-cell dysfunction using

alternate definitions of the metabolic syndrome. Dr.

Haffner’s presentation was based on data from five

studies: the San Antonio Heart Study (SAHS), IRAS,

the Mexico City Diabetes Study, the Framingham 

Study, and NHANES

Literature on the Eiology of the Metabolic

Syndrome. Dr. Haffner said the question of clustering of cardiovascular risk factors has been talked

about for at least 35 years. The concept was developed by an Italian group in the late 1960s, and in 

the 1970s there were a variety of papers on the subject. A group in East Germany led by Hanefeld talked

about clustering of cardiovascular risk factors and

about insulin but because the literature was in

German and the wall was still up, this received little

publicity.

Reaven began the discussion about an insulin resistant syndrome, calling it syndrome X (Diabetes, 1987),

and Ferrannini (Diabetologia, 1991), and Haffner

(Diabetes, 1992) added to this. Reaven’s discussion

was based on non-obese persons with insulin resistance. Some people objected to this because in the

United States and other western countries, the 

syndrome occurred primarily in obese persons. John

Despres referred to the hypertriglyceridemic waist

(triglycerides at 176 mg/dL and a 90 centimeter

waist in men), and Peter Wilson discussed the presence of weight gain in multiple metabolic disorders

(Arch Int Med, 2000) from the Framingham Study,

while not referring to the metabolic syndrome.

Glycemia in the non-diabetic range was given as the

primary cause by Gerstein, who called it the dysglycaemic syndrome, and glycemia was also presented

in the DECODE data. There remains an issue that

needs further study about whether the syndrome is

related only to the risk factors within itself or to

cardiovascular risk factors. Subclinical inflammation

has also been presented as a factor.

Prediabetic State as Model of Metabolic

Syndrome. A prediabetic syndrome was an early

attempt at looking at the metabolic syndrome.

Basically, the suggestion was that increased cardiovascular risk factors preceded the onset of type 2

diabetes. An issue was whether it was glucose or

insulin that increased the CVD risk. In nondiabetic

subjects, people who are insulin resistant always

have slightly elevated glucose levels. United

Kingdom Prospective Diabetes Study (UKPDS) data

suggest that the relationship between glucose 

concentrations, while clearly significant related to

myocardial infarction (MI) is a lot more modest than

its relationship to microvascular disease. Dr. Frank

Hu reported (Diabetes Care 2002:25(7):1129-1134)

that in the Nurses Health Study, not only those who

were diabetic at the beginning of the 20-year 

followup had a five-fold increased risk of cardiovascular disease, but those who were prediabetics had 

a three-fold risk prior to diagnosis. In each of the

populations cited in the literature, cardiovascular

risk factors were all higher in prediabetic subjects.

Dr. Haffner explained this is important as part of the

intellectual basis for prevention of type 2 diabetes

as an important strategy as opposed to screening for

diabetes and then managing it with tight control.
DMICC ANNUAL REPORT 95 FY 2003

Insulin as a Predictor of the Metabolic Syndrome

and CHD. Dr. Haffner next addressed insulin resistance, insulin secretion, and subclinical inflammation

as predictors of the metabolic syndrome and noted

that there is some controversy about insulin levels

as a predictor of CHD, although most of the data

indicates a positive correlation. He stated that it is

known that insulin concentrations predict the metabolic disorders and also predict multiple metabolic

disorders. High absolute concentrations of LDL are

not related to baseline insulin levels, but high

insulin concentrations predict the development 

of small dense LDL.

In the San Antionio Heart Study, people with normal

glucose tolerance were followed to see whether 

they developed type 2 diabetes. At baseline, they 

had higher tryglycerides, higher HDL, higher systolic

blood pressure (BP) than prediabetics, slightly higher glucose levels but the differences were really very

small, although significant, and much higher insulin

concentration. The argument was that it was hyperinsulinemia and IR that drove this pre-diabetic

issue. After Gerstein’s data came out, the San

Antonio data was reviewed and an attempt made 

to develop a model for IR versus glucose. From a San

Antonio cohort, where there was information on surrogates of IR and low insulin secretion, and from

earlier studies of the Pima Indians and data from

Joslin, it was shown that low insulin secretion and

IR do predict the onset of type 2 diabetes. Furthermore, when these factors were combined, there was

about a 20-fold excess of incidence of type 

2 diabetes.

Next the SAHS investigators looked at 105 individuals before they became diabetic and compared

them according to IR and insulin secretion and 

traditional cardiovascular risk factors—triglycerides, HDL cholesterol, and systolic blood pressure.

Fifty-four percent were IR, 29 percent were IR but

had fairly good stimulated insulin secretion based

on the change in insulin and in glucose over 30 

minutes of a glucose tolerance test, about 16 percent

had low insulin secretion, and a little less than 2

percent had neither defect, although the latter data

has some difficulties. These subjects were Mexican

Americans and non-Hispanic whites in four groups

with identical glucose tolerance, which allowed

matching for glucose control and comparison of

those who developed type 2 diabetes. The data is

very similar across the ethnic groups. Analysis of

the data strongly suggests that among prediabetics

as a model, it is IR, not small changes in glucose 

levels, that predicts type 2 diabetes.

The two groups with matched glucose and with high

IR had higher rates of conversion to diabetes and

much higher tryglycerides than those with low

insulin secretion who converted, even when stratified and controlled for weight differences. Those

with low insulin secretion who converted to diabetes

had tryglycerides similar to non-converters. There

was a similar pattern with HDL cholesterol and 

systolic blood pressure, in that those with low 

secretion tended to have similar blood pressure and

HDL levels to those who did not convert. These low

secretion converters and the nonconverters had

lower blood pressure and higher HDL levels than

those with IR who converted. LDL data on these

groups also was similar. Dr. Haffner also presented

data from a 25-year followup study reported by

Pyorala et al. (Circulation, 1998; 98:398-404) that

showed that nondiabetic men with the highest IR

are at greatest risk for a major CHD event.

Subclinical Inflammation as a Predictor of the

Metabolic Syndrome and CHD. With regard to CRP,

Dr. Haffner referred to a 1992 consensus conference

sponsored by the American Heart Association (AHA)

and the Centers for Disease Control and Prevention

(CDC). The participants discussed the relative risk of

CVD as predicted by markers of inflammation. Their

recommendations (see Pearson et al., Circulation,

2003; 107:499-511) adopted the following CRP cutpoints: high-sensitivity as 3 m/L or higher (in mg/dL

this would be 0.3 mg/dL), low as less than 1 mg/L,

and average as 1 to 3 m/L.

In the IRAS study with nondiabetics, data adjusted

for demographics (age, sex, clinic, ethnicity) and

smoking (because smoking is related to high CRP
DMICC ANNUAL REPORT 96 FY 2003

levels and some people think it is related to IR as

well), showed a strong correlation of CRP with obesity and waist circumference, a positive association

with fasting insulin levels, a significant but weaker

relationship with systolic blood pressure and fasting

glucose, and an inverse relationship with insulin

sensitivity directly measured by frequently sampled

intravenous glucose tolerance tests. The original

comparison was made prior to the NCEP definition,

but was redone using the NCEP definition and 

the WHO definition, with similar results—the 

higher the CRP level, the greater the number of 

metabolic disorders.

Dr. Haffner also referred to six studies on the 5-year

incidence of type 2 diabetes stratified by quartiles 

of three inflammatory proteins—fibrinogen, CRP,

and PAI-1—that showed that high CRPs predict 

type 2 diabetes, in some circumstances independent

of fasting insulin, although not significantly when

adjusted for IR. PAI-1 (plasminogen activator

inhibitor-1) levels were a stronger predictor, but 

Dr. Haffner said PAI-1 is unlikely to be used for 

clinical purposes because of collection and 

measurement issues.

Effect of Insulin-Sensitizing Interventions on

Reducing CRP Levels. Dr. Haffner cited Diabetes

Prevention Program (DPP) unpublished data presented at an AHA meeting in 2002 that showed 

that two insulin-sensitizing interventions, modest

lifestyle changes and metformin, reduced CRP levels

by 58 percent and 31 percent, respectively, in this

impaired glucose tolerance cohort. Lifestyle changes

caused the most lowering of CRP levels in both 

genders, but were most significant in women who

tend to have higher levels than men. The lowering 

of CRP by lifestyle and metformin continued to

increase for women over the 12-month period. Dr.

Haffner indicated that, although the data covers 

only 1 year, it suggests that lifestyle changes that

produce greater changes in type 2 diabetes may also

have greater effects on CVD. The use of rosiglitazone,

a TZD (thiazolidinedione), with diabetics, a different

population than that of the DPP, showed a 25 percent

reduction in triglycerides, similar to most statin

studies (see Circulation 2002;106:679-684).

Elevated CRP Levels as Predictors of the NCEP

Metabolic Syndrome. Data from the Mexico City

Diabetes Study indicates basically no relationship 

in men between CRP levels and development of the

metabolic syndrome and a very limited relationship

to development of type 2 diabetes. In women, those

in the lowest quartile of CRP levels have about a 7

percent chance of developing the syndrome over a 

6-year period, whereas those in the higher quartile

have about a 3.5-fold increase in risk. CRPs predict

the metabolic syndrome in both lean and obese

women, indicating that obesity, whether determined

by BMI or waist circumference, plays a strong role

as a predictor aside from CRPs. Dr. Haffner 

recommended that additional studies with other

populations be conducted to examine whether 

testing for CRP would be helpful in determining 

risk of developing the metabolic syndrome in

women, independent of BMI and HOMA-IR.

Relationship of Inflammation to Increased IR 

vs. Decreased Insulin Secretion in the PreDiabetic State . Dr. Haffner noted again that in 

the IRAS, those with high IRs who converted to type

2 diabetes had high CRP levels The high IR/high 

CRP group was also more overweight than the other

two groups. There was basically no difference in

CRP levels in those with low secretion but no IR

who developed diabetes regardless of their BMI.

However, the non-converters with high BMI also

tended to have higher CRP levels, though not as 

high as the converters with high IR. Because glucose

levels were similar in all the groups, Dr. Haffner said

this strongly suggests that IR is the major factor 

in predicting type 2 diabetes, but this is a complicated area because most people think that among the

principal determinants of subclinical inflammation 

(CRP is produced by the liver) are cytokines pro-
DMICC ANNUAL REPORT 97 FY 2003

duced in adipocytes such as IL6 and TNF-alpha 

but many of the interventions that lower CRP do 

not actually decrease IL6 in studies, possibly for 

measurement reasons.

Factor Analyses From the Framingham Study and

IRAS. The basic conclusion from factor analyses of

the Framingham study reported by Dr. Meigs in

Diabetes in 1997 and the IRAS analyses described 

by Dr. Anthony Hanley in Diabetes in 2001 is that

hypertension is a separate factor not associated 

with IR. Framingham also included a glucose factor.

In IRAS, there was a metabolic factor that included

adiposity, triglycerides, and glucose levels. IRAS 

also concluded that, along with hypertension, there

was PAI-1 that entered into the metabolic factor 

and a separate inflammatory factor with CRP and

fibrinogen. According to Dr. Haffner, it does not 

look like IR is responsible for all of these factors,

such as hypertension.

Prevalence of Metabolic Syndrome, Diabetes,

and CHD Based on NHANES III and Other Study

Data. Dr. Haffner said that according to a paper 

by Charles M. Alexander et al. to be published in

Diabetes, of which Dr. Haffner is an author, 85 percent of diabetics have the metabolic syndrome based

on NHANES III. The overall risk for CHD appears to

be intermediate between diabetes with and without

the metabolic syndrome. In the NHANES population,

the risk of CHD in those with metabolic syndrome

but no diagnosed diabetes is approximately 14 percent and approximately 19 percent in those with

both the syndrome and diabetes. The risk without

the syndrome or diabetes is 8.7 percent and without

the syndrome, but with diabetes, the risk is 7.5 

percent. Of interest to Dr. Haffner was the relatively

small number of diabetics who do not have the

metabolic syndrome and whose risk of CHD is 

very close to that of nondiabetics without the 

syndrome. This is probably not a surprise, since

hypertension is a well-known risk factor for CHD

among diabetics.

Four other databases, including data from a large

European and American pharmaceutical study in

new diabetics called ADOPT (A Diabetes Outcome

Progression Trial), whether one uses the NCEP or 

the WHO definition, indicate that somewhere

between 75 and 80 percent of diabetics have 

metabolic syndrome. These numbers appear to be

equally true in populations where obesity is less

common than in the United States, as in some 

areas in Europe.

Prediction of CHD based on multivariate logistic

regression analysis of NHANES data do not show

that the metabolic syndrome predicts CHD independently of its individual components. However,

the individual components that have a higher correlation as risk predictors are low HDL, high blood

pressure, and diabetes, which is similar to the 

information provided by Dr. Meigs’ Framingham

data. Therefore, some of the components of the 

metabolic syndrome may be more related to CHD

than are other components.

Comparison of characteristics among the U.S.

population age 20 and older with and without the

metabolic syndrome are similar whether the WHO 

or NCEP definition is used and the IR is similar to

Framingham data. Although the 1998 WHO definition

includes HOMA-IR data and the 1999 definition

involves IR as clamp-assessed glucose uptake, the

comparisons are based on HOMA-IR because no one

had clamp data. When a different measure of insulin

sensitivity is used, there is a different answer, as

discussed below.

Identification of Subjects With IR and Beta-Cell

Dysfunction Using Alternate Definitions of the

Metabolic Syndrome. In IRAS, Dr. Haffner said 

data on the lowest quartile for insulin sensitivity in

three different population groups of nondiabetics—

African Americans and non-Hispanic whites and

Hispanics, all of whom were actually Mexican

Americans—were examined to determine how well

the metabolic syndrome identified persons with IR
DMICC ANNUAL REPORT 98 FY 2003

but without diabetes as a criteria for comparing the

NCEP and WHO definitions. Unlike the Framingham

and NHANES data that look at surrogate measures,

direct measurement of insulin sensitivity presented

a different study. The group with the lowest sensitivity met neither definition. About half the population

with insulin sensitivity met both definitions, and

about one-quarter with sensitivity met one or the

other definition. Combining the criteria of the definitions made no difference. The WHO definition was

better than the NCEP in identifying persons with IR.

Overall, the direct measurement of insulin sensitivity was better than HOMA-IR or any of the NCEP 

or WHO surrogate measures in identifying those

with IR.

In looking at the measure of insulin secretion in

IRAS nondiabetics, the metabolic syndrome did 

predict people with low insulin secretion, with 

NCEP being a better predictor than WHO. Dr.

Haffner pointed out that of special interest in this

data is that the NCEP definition identified a group 

of nondiabetic African Americans with insulin 

secretory defects, and there is literature that indicates that not only does this population have IR as 

a cause for their increased rate of developing type 2

diabetes, but there may be lower glucose effectiveness and lower insulin responses in African

Americans. Dr. Haffner suggested further analysis 

is needed in this area.

In conclusion, Dr. Haffner remarked that the characteristics of the metabolic syndrome need to be

reexamined based on the data from the IRAS. Using

directly measured IR across three different ethnic

groups, the WHO definition was better than the

NCEP as a predictor of IR, but whether this is 

significant enough is another matter. Obesity is a

significant factor in the United States, IR has data

that suggests it is and is not important, and 

subclinical inflammation appears to be important

according to experimental work in epidemiology.

IR is certainly not the cause of the entire syndrome,

but it does seem to be a contributing factor, according to Dr. Haffner.

Scott M. Grundy, MD, PHD, Director, Center for

Human Nutrition, Professor of Internal Medicine,

Chairman, Department of Clinical Nutrition,

University of Texas Southwestern Medical 

Center at Dallas

Issues for Prevention and Treatment of the

Metabolic Syndrome

Dr. Grundy served as Chair of the NHLBI’s National

Cholesterol Education Program (NCEP) Expert Panel

on Detection, Evaluation, and Treatment of Blood

Cholesterol in Adults (Adult Treatment Panel III).

He opened his presentation by explaining that the

NCEP ATP II committee and panel members involved

in developing LDL cholesterol guidelines to prevent

and treat coronary heart disease (CHD) were concerned about a nutritional approach along with the

drug treatment approach that clinical trials had

shown could reduce the risk for CHD. ATP II thus

addressed obesity and physical inactivity, but this

was not really noticed. The increasing evidence 

that obesity and physical inactivity leads to CHD

prompted the ATP III members to take a new

approach. Concerned that the NCEP guidelines

would be seen as only drug treatment guidelines 

for LDL, they decided to define a set of medical conditions related to obesity, physical inactivity, and

nutrition and define these conditions as a metabolic

syndrome. Based on the prevalence of CHD and its

mortality rate in those with type 2 diabetes, the

panel also elevated type 2 diabetes to a CHD risk

equivalent or high-risk condition. The intention was

to get physicians to pay more attention to their

patients at risk for both CHD and diabetes because

of lifestyle-related problems. Therefore, the guidelines addressed high LDL, the cluster of medical

conditions termed metabolic syndrome, and type 2

diabetes that tends to result from or accompany 

the syndrome, as being high-risk factors for CHD.

Dr. Grundy stated that by defining a syndrome,

rather than merely further emphasizing obesity 

and physical inactivity as CHD and diabetes risk

factors, ATP III has successfully moved forward in

acquiring attention about these risk factors.
DMICC ANNUAL REPORT 99 FY 2003

Dr. Grundy stated that it is known through the 

literature reports of clinical studies that therapeutic

lifestyle changes do correct or at least modify all 

of the metabolic syndrome risk factors (excess fat 

in adipose tissue and abdominal fat, high blood

pressure, high triglycerides, low HDL, insulin resistance, high PAI-1, and high CRP). These reports also

show that drug treatment is a potential approach to

managing the individual components such as using

aspirin and hypertensive drugs for the prothrombotic state, the insulin-sensitizing drugs such as

metformin and the TZDs for insulin resistance, the

lipid-lowering drugs to reduce the proinflammatory

state , and drugs besides statins for patients with

atherogenic dyslipidemia. Factors in favor of drug

therapy for the metabolic syndrome would be highrisk individuals such as those with established CVD

and/or type 2 diabetes, persons with multiple risk

factors, and also moderately high-risk patients 

who have a 10-year risk in this range according to

ATP III guidelines.

Issues for Prevention and Treatment of the

Metabolic Syndrome. Dr. Grundy listed public

health and clinical strategies as key issues for the

prevention and treatment of the metabolic syndrome. In clinical strategies, it is important to 

know about risk assessment in patients with the

syndrome, selection of patients for interventions,

both lifestyle, which was made the major part of 

the ATP III guidelines related to metabolic syndrome, and pharmacological intervention. Prevention

and therapy issues include defining the syndrome,

determining its prevalence, identifying the metabolic

components or risk factors and potential treatment

targets, assessing the health consequences of these

components, and understanding the pathophysiology

of the syndrome.

What Is the Metabolic Syndrome? Dr. Grundy

noted that definitions of the metabolic syndrome

have come from several areas, each of which has

particular implications for prevention and treatment

of the metabolic syndrome.. The syndrome has been

defined according to clinical outcomes (CHD and 

diabetes), in relation to underlying causes such as

insulin resistance or obesity; by its metabolic 

components as in the ATP III clustering of metabolic

cardiovascular risk factors, and according to 

clinical criteria as in the NCEP definition based on

cardiovascular disease (CVD) risk factors and the

WHO definition based on insulin resistance as an

underlying cause.

Implications for Therapy and Intervention Based

on Definitions of the Metabolic Syndrome. Dr.

Grundy stated that how the metabolic syndrome is

defined has implications for therapy and intervention in patients identified with the syndrome. When

defined by insulin resistance as the underlying

cause, the metabolic syndrome is often called the

insulin resistant syndrome. When lifestyle, especially obesity, is considered the major underlying cause,

the concept is known as the metabolic syndrome.

Each viewpoint results in different treatments.

Implications Based on Clinical Outcomes. The 

cardiovascular area sees the metabolic syndrome 

as primarily a precursor or risk factor for cardiovascular disease and treats it to prevent CHD. Those in 

the diabetes field view it as mainly a precursor or

predisposing factor for type 2 diabetes and look 

on it and treat it as pre-diabetes. (Dr. Grundy

acknowledged that this is not the ADA definition for

pre-diabetes.) For lifestyle interventions, each viewpoint’s therapeutic implications are much the same,

but for pharmacological interventions, there is 

generally divergence of these two pathways.

Implications Based on Components or Risk Factors.

A variety of components have been identified as

being associated with metabolic syndrome, such 

as those in the ATP III definition: atherogenic dyslipidemia (high triglycerides, perhaps increased

apoliprotein B (apo B), small LDL, and low HDL);

raised blood pressure; insulin resistance with or

without hyperglycemia; a proinflammatory state;

and, increasingly, the prothrombotic state, which

many people see as the dominant component,

whereas from the cardiovascular point of view, these

other factors are equally important. Therapeutic

implications according to this definition see all 
DMICC ANNUAL REPORT 100 FY 2003

these components as potential targets of treatment

and management, independent of the underlying

causes. For instance, in addition to treating high

triglycerides, low HDL, and blood pressure, there is

a great deal of current interest in directly targeting

the proinflammatory state as a separate approach 

to reducing cardiovascular risk. It is also known 

that through aspirin or any platelet therapy, the 

prothrombotic state can be reduced.

Implications Based on Underlying Causes and

Clinical Criteria. The NCEP ATP III definition was

based on obesity, especially abdominal obesity, as

the primary factor that gives rise to the other four

components as a CVD risk, whereas the WHO definition emphasized insulin resistance as the underlying

cause. Although not specifically requiring abdominal

obesity as a requirement, the ATP III definition’s

clinical criteria and therapeutic strategy was meant

to focus on obesity and its treatment, and the public

health strategy was to prevent obesity in the general

population, which is the approach of the NHLBI/

NIDDK Obesity Education Initiative. However, there

has been a developing interest in the field in focusing on treating the individual metabolic components,

which has implications for the use of drug therapies.

The WHO definition’s clinical criteria places more

emphasis on the genetic basis of the syndrome,

rather than obesity. The WHO requirement of IR or

one of the glucose abnormalites (IFG, IGT, diabetes)

for the diagnosis places the therapeutic focus on the

use of drugs to treat patients with the metabolic

syndrome. Dr. Grundy noted that this use of drug

therapy concerns many people in discussing the

value of the metabolic syndrome as a means of 

identifying CVD metabolic risk factors and of recommending interventions to prevent development of 

the disease.

Implications of Including Type 2 Diabetes in the

Definition. Dr. Grundy noted that inclusion of type 2

diabetes in the definition of the metabolic syndrome

also has important therapeutic implications. The

NCEP and WHO include it. The American Academy 

of Clinical Endocrinologists (AACE) and Framingham

analysis do not. If included, clinical intervention will

be emphasized more, including greater emphasis on

drug therapy for the CVD risk factor components

once the patient has developed type 2 diabetes.

Clinical trials have provided evidence of the benefits

of such drug therapy. This also raises the question 

of when should drug therapy for the individual risk

factors be introduced in the pre-diabetic state.

Prevalence of the Metabolic Syndrome and

Implications for Therapy and Intervention.

NHANES III data reported by Dr. Earl Ford of the

Centers for Disease Control and Prevention (CDC) 

in the Journal of the American Medical Association

(JAMA) (Ford et al. JAMA 2002;287:356-359) shows

the rising prevalence of the metabolic syndrome 

by age regardless of gender. Dr. Grundy pointed out

that, although the prevalence of individual components varies, the magnitude of the problem and the

relevant issues for clinical management and public

health are evidenced by the fact that approximately

24 percent of 47 million U.S. citizens have at least

three of the abnormalities defined by the metabolic

syndrome. Some populations, such as Hispanics,

Mexican Americans, Asians, particularly South

Asians, and African-American women, have even

higher prevalences. In the NHANES III period

between 1990 and 1999, diabetes rates as an outgrowth of the metabolic syndrome increased at an

alarming rate, particularly in young adults. Dr.

Grundy stated that there are as many people with

diabetes in the United States as with established

CHD, making these two diseases basically equal for

development of metabolic and cardiovascular complications in the U.S. population.

Implications for Intervention. The fact that 47 

million people have the metabolic syndrome and 18

million have type 2 diabetes appears to indicate that

one-third or more of persons with the metabolic

syndrome will develop diabetes, which has serious

public health and therapeutic implications. This is

true for young adults, older adults, ethnic populations, and women.
DMICC ANNUAL REPORT 101 FY 2003

There is a relatively high prevalence of the metabolic

syndrome among young adults and, in the decade of

1990-1999, there was a 76 percent increase in type 2

diabetes in adults between the ages of 30 to 39. Dr.

Grundy directed the audiences’ attention to the 

CARDIA study that points out the dangers of early

development of the metabolic syndrome and its risk

factors. He stated that the current 35-45 percent

prevalence of the metabolic syndrome in middleage and older people indicates the need to focus

attention on public health strategies that target 

adolescents and young adults to reduce the burden

of the syndrome in the future. It also means clinical

strategies are needed to identify and provide interventions for the substantial number of persons

already affected by the syndrome, and it may possibly indicate the need for public health strategies for

this group.

Dr. Grundy urged that more attention be paid to the

health consequences of the metabolic syndrome in

the ethnic populations who appear to be prone to

the syndrome and that additional research be conducted on interventions for these high-prevalence

groups. With regard to CVD, Dr. Grundy said he 

suspects that the metabolic syndrome may be a

dominant cause of cardiovascular disease in women

in all ethnic groups. The Framingham Heart Study

indicated that although women are at lower risk for

CVD, the metabolic syndrome is very common among

women who develop CVD. NHANES indicates that

the metabolic syndrome is equally prevalent in men

and women, and the risk for type 2 diabetes in those

with metabolic syndrome is also about equal.

Components of Metabolic Syndrome and

Relationship to CVD. From accepted guidelines, it 

is known that the intensity of any therapy should be

proportionate to the level of risk. Therefore, it is

extremely important to know the risk of the metabolic syndrome for both development of CVD and

diabetes. Each of the components of the metabolic

syndrome are connected in some way but vary in

their relative risk for developing CHD and work

through different mechanisms. Dr. Grundy noted

that there is increasing evidence that each of the

metabolic syndrome components are in some ways a

separate risk factor for either atherogenesis or acute

coronary syndromes. If that is the case, then each of

the components as a metabolic risk factor is a

potential target for a lifestyle or drug therapy intervention.

According to Dr. Grundy, this is an area that needs a

lot more investigation. The data may already be contained in the Framingham study and other studies,

but it needs to be mined, analyzed, and studied to

better understand the absolute risk associated with

the metabolic syndrome for these two conditions.

Framingham suggests that people with the metabolic syndrome are perhaps at 2 to 3 times higher risk

for CHD, although this needs to be analyzed in more

detail. The results of the Finnish study also indicate

that coronary mortality is much higher in patients

with the syndrome than in those without it (Laska et

al., JAMA 2002; 288:2709-2726). In a study reported

by Norhammar et al. (Lancet, 2002; 359:3140-2144),

the majority of acute myocardial infarctions (MIs)

occur in people with unrecognized abnormal glucose

tolerance. Dr. Grundy says this needs to be confirmed but is of great interest. In the Norhammer

study, among 200 patients admitted to a Swedish

hospital with acute MI, 20 percent had established

diabetes, another 33 percent without known diabetes

actually had diabetes according to an oral glucose

tolerance test (OGTT), and another 31 percent had

impaired glucose tolerance. Only 35 percent of the

so-called normals (those without known diabetes)

actually had normal OGTTs. Dr. Grundy pointed out

that this report indicates there is a high prevalence

of metabolic disorders in patients who have acute

coronary syndromes or MI, and it illustrates the

importance of glucose and insulin abnormalities in

patients with CVD, factors that should certainly help

bring the two fields together.

Metabolic Syndrome and Risk for CVD. Dr. Grundy

spoke of the confusion that exists about the ATP III

guidelines and the metabolic syndrome as a risk for

CVD. He said it is important to clarify this because

of the possible pharmaceutical versus lifestyle 

interventions that would result based on a miscon-
DMICC ANNUAL REPORT 102 FY 2003

ception. Some people mistakenly believe that the ATP

III defined the metabolic syndrome as a CHD risk

equivalent, which it did not do. ATP III did identify

type 2 diabetes, or diabetes in general, as a high-risk

condition for CHD. Dr. Grundy recommended further

study of Framingham and other databases to determine the absolute risk of CHD among patients with

the metabolic syndrome.

Type 2 Diabetes and Risk for CHD. One of the 

reasons ATP III identified type 2 diabetes as a high

risk condition for CHD is that CVD is the number

one cause of death in type 2 diabetes and probably

in type 1 diabetes also. Furthermore, there is a high

10-year risk in diabetics for developing CHD, a high

lifetime risk, and nearly twice the risk of mortality

after MI compared to nondiabetics after MI.

Relationship of Diabetes to Obesity. NHANES III

showed that as the body mass index (BMI) increases

in U.S. adults ages 20-49, so does the prevalence of

diagnosed diabetes, especially when the BMI is 35 or

more. In adults over the age of 50, 23 percent of

those with a BMI equal to or greater than 35 have

diabetes. There is also a very high incidence of IR in

those with obesity, somewhere in the range of 85-90

percent. Not all of these persons will develop the

beta cell dysfunction that leads to hyperglycemia

and type 2 diabetes, perhaps only 15 to 20 percent.

The relationship between obesity and type 2 diabetes is certainly not universal, as it appears to be

with IR, because it requires a second factor. This has

implications for intervention. Dr. Grundy stressed

that although the majority of people with obesity

and IR do not develop type 2 diabetes, nonetheless

prevention of obesity in the general population will

reduce the prevalence of type 2 diabetes and this is

a worthy goal. He added that the relationship of diabetes to obesity perhaps also indicates the need for

early detection of glucose intolerance to aid in the

selection of patients for prevention of type 2 diabetes beyond just the identification of the obese

individual.

Pathophysiology of the Metabolic Syndrome and

Implications for Intervention. Dr. Grundy divided

the pathophysiology of the metabolic syndrome into

two major areas—upstream abnormalities such as

underlying causes, particularly adipose-tissue disorders, and downstream abnormalities such as the

responses in the risk factors to the underlying 

causes, possible risk factors specific to genetic

abnormalities, and ethnic characteristics that determine the expression of the metabolic syndrome in

the presence of these upstream underlying causes.

Adipose tissue disorders include (1) excess fat in

adipose tissue (obesity), (2) lipodystrophies where

there is a deficiency of adipose tissue, (3) abdominal

fat distribution (abdominal obesity), and (4) primary

IR of adipose tissue, which is a separate and perhaps genetic factor that may or may not be present

in people with these other disorders. There is a 

public health approach for the general population

dealing with excess fat or obesity and clinical therapeutic guidelines for lifestyle changes in the

NHLBI/NIDDK Obesity Education Initiative, which

did not have as a primary focus the subsequent risk

factors associated with obesity, although there was

more emphasis on clinical intervention in overweight people when risk factors were present. Since

a third of overweight/obese Americans have the

metabolic syndrome according to NHANES III, Dr.

Grundy believes these patients need special attention for clinical detection and probably more intensive intervention.

Dr. Grundy said that lipodystrophy, which comes in

several forms, is an interesting model for the metabolic syndrome. When there is a deficiency of adipose tissue, there is a redistribution of fat between

adipose tissue that in many ways serves as a storage

or even protective organ and fat distributed into

muscle and liver, which gives rise to the syndrome.

Patients with lipodystrophy usually manifest the

metabolic syndrome. The congenital, rare lipodystrophies have been studied at NIDDK and by Dr.
DMICC ANNUAL REPORT 103 FY 2003

Abhimanyu Garg at the University of Texas

Southwestern Medical Center. There are also partial

lipodystrophies (lamin A/C mutations, PPAR (peroxisome proliferative-activated receptor) gamma 

mutations, HIV lipodystrophy) that are associated

with the metabolic syndrome. The HIV lipodsytrophy

associated with the metabolic syndrome is quite

common and presents a therapeutic dilemma for

physicians taking care of HIV patients. Dr. Grundy

said that research is needed in this area from a clinical viewpoint and also may provide important

information about how to approach the metabolic

syndrome in other situations.

In speaking of fat distribution patterns, Dr. Grundy

said there is a lot of clinical evidence that patients

with lower body (gluteofemoral) obesity have a lower

prevalence of the metabolic syndrome than those

with upper body obesity. Different kinds of upper

body obesity is perhaps related to different metabolic syndrome components and different implications

for therapy. Some people who have upper body obesity and predominantly subcutaneous fat are at

increased risk for diabetes. Those with predominantly visceral fat also are at increased risk and more

prone to develop dyslipidemia. Dr. Grundy stressed

that if abdominal obesity as a risk factor for the

metabolic syndrome is important, then there is a

need to encourage waist measurement in the clinical

setting to help identify these high risk patients. He

added that perhaps there also is a need for intensive

testing for the presence of the metabolic syndrome

with abdominal obesity and, if present, then more

aggressive intervention for weight reduction and

treatment of risk factors.

Next Dr. Grundy addressed primary IR of adipose

tissue and generalized IR that extends to adipose

tissue. When this occurs, often on a genetic basis,

there is an excessive release of NEFA (non-esterified

fatty acids) in circulation and other adipocyte products associated with mild obesity, which gives rise

to this syndrome. Certain populations are at high

risk for this type of abnormality, particularly South

Asians, who are very insulin resistant on a genetic

or racial basis and who have the metabolic syndrome, premature CHD, and diabetes at exceptional

rates. Studies also show that offspring of diabetic

parents tend to be insulin resistant and manifest the

syndrome even with mild obesity and patients with

primary hypertriglyceridemia probably also have an

underlying IR and adipose tissue that leads to this

hypertriglyceridemia. So there is a high prevalence

of the metabolic syndrome even in the presence of

mild obesity, which illustrates the problem of using

obesity as the only factor in identifying the metabolic syndrome in some individuals. Dr. Grundy stated

that it remains to be seen how far to stress this in

the clinical area. Perhaps there is a need to identify

IR with minimal abdominal obesity in a subpopulation of people or perhaps in certain population

groups because even mild obesity in persons who

have IR by this mechanism accentuates their risks

and should be a target for treatment by weight

reduction and possibly even TZDs, although he did

not advocate the latter.

According to Dr. Grundy , genetic factors contribute

to all the metabolic syndrome components—

atherogenic dyslipidemia (high triglycerides, high

apo B, small LDL, low HDL), hypertension, hyperglycemia, the proinflammatory state, and the 

prothrombotic state.

General Discussion of the Morning Presentations

The general discussion that followed the presentations addressed the definitions of the metabolic syndrome and its etiology, prevalence of the syndrome,

the relationship of the syndrome to risk for CVD and

diabetes, and implications for prevention and therapy. An overall major issue was the heuristic value of

the syndrome.

Definition of the Metabolic Syndrome and Its

Etiology. Dr. Peter Savage, NHLBI, remarked that it

was likely that there are multiple causes of the

metabolic syndrome, which may be difficult to identify, and even the possibility of the chance concurrence of common risk factors in a given individual.

On the other hand, data from the CARDIA study indicates that people who have multiple risk factors
DMICC ANNUAL REPORT 104 FY 2003

tend to persist in having multiple risk factors over

time. So from a pragmatic point of view, regardless

of the etiology, the metabolic syndrome has significance by defining the development of risk later on 

in life. Dr. Savage said that a pragmatic definition is

therefore important and useful, even without universal agreement on what the exact criteria of the

metabolic syndrome should be.

Dr. Judith Fradkin, NIDDK, suggested that perhaps

rather than defining the cluster of risk factors as the

metabolic syndrome, the same purpose of achieving

recognition and attention for the clustering might

be accomplished by using the data to develop a continuous and individualized risk engine. Persons

could then view their personal risk engine and learn

what losing 10 pounds by walking could do in

reducing their own risk of developing diabetes or

heart disease. This might motivate people as much

as presenting them with a syndrome.

Dr. Grundy replied that NCEP tried very hard to get

physicians interested in using Framingham risk

scoring and even made it the core of their guidelines. However, his impression is that the metabolic

syndrome has generated a lot more interest. He is

now hoping that Framingham will include the risk

factors from the metabolic syndrome. He believes

there is something about the simplicity of the idea

of the metabolic syndrome that seems to appeal to

many people who have not yet accepted the

Framingham risk scoring, even though it is a very

powerful tool in defining cost-effective and appropriate therapies.

Dr. Grundy added that another possible component

of the metabolic syndrome might be stone disease.

It is related to obesity and insulin resistance and

there is a lot of data on the mechanisms. He felt 

that if an expanded view was to be developed, then

it would fit in as one of the complications like 

fatty liver.

Dr. Vinicor commented that viewing the metabolic

syndrome as a concept or a vehicle to increase

attention by the practitioner was one thing, but the

use of the word “syndrome” or “disease” creates a

different issue. What is required to move from a

concept to a statement that something is a syndrome or a disease is determined by experts in

nosology who classify diseases. While he agreed that

consensus on a definition was worthwhile, he felt

that it was also important to consider what is necessary to identify this cluster of conditions as a

syndrome because this has huge policy and 

financial implications that go beyond a conceptual

or methodological viewpoint. He urged the group

not to move too easily or quickly from an area that

may be intellectually important or may become clinically important to an area that is practically, financially, and public policymaking important without a

clear understanding of the implications. He referred

to conversations he has had with persons from the

Centers for Medicaid & Medicare Services about

why hypertension is a disease and high cholesterol

is not. However, whether a condition is a risk factor,

a syndrome, or a disease does have very important

implications.

Dr. Grundy said that the NCEP panel had similar

issues in defining individual risk factors. Is hypertension a symptom or a sign or a disease? Is 

diabetes a syndrome or a disease? He agreed that 

defining this concept does present problems but

thinks they are built on top of existing underlying

problems.

Dr. Haffner added that an interesting implication in

establishing guidelines is that if hypertension is a

disease then treatment is not based on the global

risk over the short-term, whereas if cholesterol is a

symptom, then global risk is calculated and considered in treating it.

Dr. Jay Everhart, NIDDK, asked if there was data on

serum leptin in regard to the metabolic syndrome,

particularly since leptin is both a marker of adiposity and a marker of inflammation. Dr. Haffner replied

that there must be, but he could not actually remember seeing it.
DMICC ANNUAL REPORT 105 FY 2003

Prevalence of Metabolic Syndrome. Dr. Frank

Vinicor, CDC, asked what was the role of the aging

U.S. population in the increased prevalence of the

metabolic syndrome based on the Framingham and

NHANES III data. Dr. Haffner answered that it would

be necessary to use broad cohorts to actually look at

that, but it would be interesting to do an analysis by

different age groups to acquire an idea of the magnitude of this increasing problem.

The Metabolic Syndrome and Risk for CVD and

Diabetes. Asked why people who have MI, both

acute and long-term, and diabetes have a mortality

rate that is double that of nondiabetics with MI, Dr.

Grundy replied that it was probably due to the presence of multiple factors such as more hypertension,

advanced atherosclerotic disease because of their

diabetes, and diabetic caridionmiopathy, which is a

complex condition. One reason it is important to

prevent heart disease in the first place in patients

with diabetes is that they are at higher risk for heart

failure once they develop established CHD and have

a very high risk of dying from the CHD.

Dr. Richard Kahn, American Diabetes Association

(ADA), asked if anyone had studied the metabolic

syndrome in a population, such as the Framingham

cohort, by adding CRP to the other components and

identifying which of the components had a greater

effect on development of CVD. Dr. Haffner replied

that a report by Dr. Paul Ridker’s group based on the

Women’s Health Study, which is a very low-risk population, only about 0.2 percent per year, indicated

that CRP was basically independent of the metabolic

syndrome as a risk factor. This may indicate that

CRP is not caused by the metabolic syndrome as

stated in many papers. Dr. Haffner’s data suggests

that CRP is a fairly good risk factor for diabetes,

not as good as glucose levels, but probably as good

as waist circumference. He added that, ironically,

some people think CRP is easier to measure than 

the waist.

Dr. Meigs explained that the Framingham risk score

is calculated as points for the presence of incrementally elevated risk factors even within the normal

range, so that a blood pressure that is mildly elevated gives a little bit of extra risk. Age is a major driver of the Framingham risk score, and what happens

with the metabolic syndrome and age is unknown,

other than that the prevalence increases considerably. Framingham only considers total cholesterol or

LDL cholesterol, but not high triglycerides. Also the

main published use of the Framingham risk score

only considers established diabetes, not impaired

fasting glucose or post-challenge glucose.

Dr. Meigs said that Framingham is working on the

question of what is added by including the metabolic syndrome criteria to the Framingham risk score.

They should have an answer in another month or

two. Dr. Meigs does not consider the current

Framingham risk score as the right tool to measure

whether the metabolic syndrome increases risk

because the metabolic syndrome captures a different

set of risk factors than the Framingham risk score.

He thought it entirely plausible that adding the

metabolic syndrome criteria to the Framingham risk

score would increase the predictive capacity fractionally because of these additional components.

Dr. Haffner stated that the Framingham risk score

handles HDL and blood pressure very well as CVD

risk factors, better than the metabolic syndrome,

because they are separate categories. Although

Framingham does not include any individual glucose

information, just the presence of diabetes, that data

and low HDL may be unimportant in calculating

CHD risk. Framingham does include waist circumference but not BMI. Dr. Haffner wondered if including BMI or weight would have served as a tool to

teach people about the importance of lifestyle

changes. Dr. Haffner agreed with Dr. Meigs that, to

his knowledge, there was no data that tested any

population adding the metabolic syndrome to the

global risk within strata to determine increase in

risk, which would be key to determining implications for therapy.

In response to a question from Dr. Kahn about the

integrity of risk levels associated with the metabolic

syndrome based on the different components and
DMICC ANNUAL REPORT 106 FY 2003

the levels of the individual components, Dr. Grundy

pointed out that there is a consensual similarity

between the metabolic syndrome and the

Framingham risk score in that they are both multrisk factor concepts. Framingham risk scoring

includes one set of risk factors; the metabolic 

syndrome has an overlapping relationship to

Framingham scoring, but goes beyond it by including obesity and triglycerides. These additional 

factors are increasingly common in the population,

and many people believe they are truly independent

risk factors. The PROCAM (Prospective Cardiovascular Münster Heart Study) algorithm being used in

Europe includes weight and triglycerides as independent risk factors. Using the PROCAM algorithm

for patients with the metabolic syndrome results in

an absolute risk somewhat different from that of the

Framingham score. Incorporating weight and triglycerides into Framingham would be a big service in Dr.

Grundy’s opinion.

Dr. Meigs addressed Dr. Kahn’s question by saying

that different trait combinations do confer risk for

different endpoints in Framingham. For example,

people with normal blood pressure but a larger

waist may have a different risk than people with elevated blood pressure and a normal waist. Another

issue is that measurement of thresholds are quite

variable; an individual would certainly require at

least two glucose measurements for the establishment of diabetes. However, a fasting glucose of 127

mg/dL twice would be clinically diagnosed as diabetes even though it is likely that the patient has a

normal hemoglobin A1c. The situation is still taken

seriously because it is known that eventually the

patient is going to have more hyperglycemia and

resultant complications. It is just the timeframe that

is longer than for a person with a higher threshold.

When thinking about metabolic risk factors, this

diabetes analogy is helpful to consider. The CARDIA

study also shows that even a person who is very,

very mildly abnormal, when tracked over time, is

identified as a person in the early stages of cardiovascular risk.

Dr. Kahn stated that ADA is looking at another kind

of modeling of the various risk factors and examining the effect caused by reducing one or the other.

For example, instead of looking at a continuum,

the model will examine a group of people who have

blood pressure or fasting glucose levels that are 

borderline but not severe, such as 130 to 140 or 110

to 125, respectively, and evaluate risk. The model 

will also evaluate risk based on whether an individual has one or more risk factors that are at high 

levels versus one or more risk factors that are at 

low levels.

Dr. David Orloff, FDA, had a question about prevalence data of the metabolic syndrome, the risk of

CVD prior to clinical diagnosis of type 2 diabetes,

and prevention versus screening and aggressive

treatment of diabetes: Dr. Haffner answered that

slides have limitations in presenting data: The

Nurses Health Study was a very large study but 

diabetes was self-reported so the actual onset was

probably earlier. Also, the data were only for women.

The lifetime risk was approximately a 20-year risk.

About 25 percent of the risk of CVD might actually

occur prior to clinical diagnosis. That is not trivial

and could be an impetus for prevention, especially 

if it is believed that lifestyle interventions have an

effect on decreasing CVD even in people who do not

develop diabetes. NHANES and Framingham data

might also be calculated to determine the population-attributable risk of people who eventually

develop type 2 diabetes. Economic analyses could

also be done. The data needs to come from populations of both genders to decide on an optimal strategy between early screening and aggressive treatment

versus prevention strategies.

Dr. Spiegel commented that the followup to the

Diabetes Prevention Program (DPP) will look at data

on this well-characterized population in which the

exact onset of overt diabetes is known and will also

look at the CVD influence. Dr. Haffner agreed that

the DPP data is very important and that hopefully

within a year there will also be atherosclerosis data

based on carotid artery intima-media thickness

(IMTs), which may provide a hint of what is happening in this area.
DMICC ANNUAL REPORT 107 FY 2003

In response to a question from Dr. Spiegel regarding

type 1 diabetes, macrovascular complications, and

inflammation, Dr. Haffner said that there would be

an NIH workshop on this subject in a couple of

months. He stated that the ideal way to study this,

and possibly NIDDK is funding this, is to look at

type 1 diabetes in adults in Scandinavia where there

is a relatively high rate of type 1 diabetes in adults,

and using registry data, match persons who develop

type 1 and type 2 diabetes at the same age and then

follow them prospectively. The problem with studying this issue in children is that it takes a long time

to develop and the risk is very low. It could be done

with atherosclerosis studies, since there is so much

type 2 diabetes starting to occur in adolescence in

the United States and the progression of atherosclerosis is known. Dr. Haffner assumed that those with

type 2 diabetes would have more disease because

they are much more obese than persons with type 1

diabetes when matched for age. In the Diabetes

Control and Complications Trial (DCCT), the early

data on IMTs did not show a difference between

those with type 1 diabetes and normal controls. The

progression data may now be showing an acceleration, but Dr. Haffner is not on that review panel and

so does not have that data. Dr. Fradkin added that

surrogate measures from DCCT do indicate clear 

differences between the treatment groups in terms

of progression.

Implications for Therapy. Dr. Malozowski noted

that even in patients with established diabetes,

long-term compliance with lifestyle changes is difficult to achieve. For persons who have the metabolic

syndrome but have not been diagnosed with diabetes or CVD, he asked what interventions are necessary and practical. Even though lifestyle changes

have been shown to be an excellent approach, the

potential of using different medications has also

been discussed. Among these are the TZDs, which

provide improvements in some of the metabolic

aspects but are known to increase weight gain,

sometimes substantial weight gain.

Dr. Haffner replied that the TZD issue is two issues:

the diabetic issue and the non-diabetic issue. The

diabetic issue is less problematic to some degree

because the TZD does lower glucose. While all diabetes drugs have their own limitations, if you use

conventional definitions of the metabolic syndrome,

whether WHO or NCEP, TZD, in spite of the weight

gain, will improve the metabolic syndrome. They

raise HDL, are slightly beneficial or neutral for

triglycerides, claim to lower blood pressure, and

clearly improve insulin sensitivity. Several studies,

some of which are NIH-funded and some that are

pharmaceutical studies, are looking at the long-term

effects of TZDs on diabetes. BARI2-DM (Bypass

Angioplasty Revascularization Investigation and

Diabetes Mellitus) will presumably collect information on weight gain and will compare sensitizing

versus insulin providing drugs. ADOPT (A Diabetes

Outcome Progression Trial) is probably the clearest

in terms of weight gain and waist circumference and

will resolve some of the issues that measure lipids

in the components. However, this does not mean 

that these agents are better for CVD, according to 

Dr. Haffner, which is a real limitation for their use.

There are very few trials, here or abroad, competently looking at this issue of paying to take a medication that may or may not be more effective than

lifestyle modification for diabetes and may not be

effective for CVD. Dr. Haffner said that he thought

the Food and Drug Administration (FDA) should

require companies to do endpoint studies if they

want to treat non-diabetics with insulin sensitizers

rather than rely on a “leap of faith.”

Dr. Jay Everhart, NIDDK, inquired whether the DPP

has looked at changes in the metabolic syndrome

constellation following the lifestyle intervention. In

terms of the public health aspect, it would be very

attractive to show an effect of lifestyle intervention

on this constellation. Dr. Haffner referred to a paper

submitted to ADA by Dr. Robert Ratner that presents

statistically significant blood pressure, triglyceride,

and HDL changes but does not calculate the metabolic syndrome at the beginning and end of the
DMICC ANNUAL REPORT 108 FY 2003

study. The prevalence of the syndrome in the DPP

cohort was about 60 percent. The study subjects 

had to have impaired glucose tolerance (IGT) and 

a fasting glucose of 95 mg/DL or higher. Dr.

Haffner assumed that the numbers went down 

with the lifestyle intervention. Dr. Kahn said the

biggest change was in triglycerides; blood pressure

went down a fair amount in the first year but less at

the end of the 3 years when the subjects regained

some weight.

Heuristic Value of the Metabolic Syndrome. Dr.

Spiegel remarked that the metabolic syndrome is

basically a concept involving a very heterogeneous

set of disorders with undoubtedly many underlying

genetic sequence variations and environmental

interactions. He noted that much of this will become

clearer after Dr. Francis Collins of the National

Human Genome Project provides the sequence on a

chip. Meanwhile, based on the current definitions of

the syndrome, Dr. Spiegel asked what is the real

heuristic and practical value of the metabolic syndrome. The syndrome presents a constellation of

treatable abnormalities, whether they be lipid

abnormalities, hypertension, or glucose abnormalities. Is this an issue of defining different cutpoints

that would then lead to treatment with drugs? What

is being learned? What is the practical significance

of this concept of a metabolic syndrome?

Dr. Grundy responded that one of the reasons the

metabolic syndrome was introduced or emphasized

in the ATP III guidelines was to get physicians to

pay more attention to the medical aspects of obesity

and its complications, which were being ignored.

Obesity had tended to be considered as something

one could do little about in a clinical setting. If the

metabolic syndrome could draw attention to people

who have risk factors that converge and emerge

from the presence of obesity, then physicians might

begin to internalize this idea, pay more attention to

it, and make it more meaningful in their practice.

Dr. Haffner spoke of the many databases that

include the components of the metabolic syndrome

or the modified metabolic syndrome, but few papers

that discuss the interrelationship of these components. He added that people pay little attention to

behavioral aspects, but if they become convinced

that this is an important syndrome whatever their

actual risk, and if lifestyle interventions are relatively more effective for this syndrome than are drugs,

which he thinks is likely to be true, then they just

they might do the right things, even if not exactly for

the right reasons, which would make this a useful

concept. The concern Dr. Haffner sees people struggling with is whether this is this going to lead to a

huge explosion of drug therapy and the use of new

drugs in non-diabetic patients because they have the

metabolic syndrome.

Dr. Meigs, as a primary care doctor and researcher,

said he thinks the value is two-fold. First, defining

the metabolic syndrome helps to focus attention on

the importance of mildly elevated risk factors in

combination as being important targets for some

form of intervention, rather than ignoring mildly 

elevated blood pressure or mildly abnormal lipid

levels. Defining the syndrome also crystallizes the

concept of multiple risk factors occurring together

as being worthy of some form of intervention. It provides a handle on obesity as a target for intervention

in terms of treating the related risk factors as

defined by the metabolic syndrome. Historically, obesity is difficult to deal with and clinically doctors

tend to view it as not their problem. For these reasons, Dr. Meigs felt it was valuable to move toward 

a consensus definition. on how to actually define it.

Secondly, the etiology of the syndrome seems to

derive largely from lifestyle issues that arise in

childhood and adolescence. It is, therefore, important to address these issues early. The issue of treating basically asymptomatic, otherwise healthy people with drugs to prevent development of a disease

10 or 20 years in the future requires serious evaluation, especially in the setting of emerging data that

lifestyle changes are so effective in preventing at

least diabetes.
DMICC ANNUAL REPORT 109 FY 2003

Agency Presentations

National Institute of Diabetes and Digestive and

Kidney Diseases

Judith Fradkin, MD, Director of Division of

Diabetes, Endocrinology, and Metabolic Diseases

Dr. Fradkin stated that NIDDK is not specifically

investigating the metabolic syndrome, but the

Institute is conducting programs indirectly related

to it such as the Diabetes Prevention Program (DPP).

In February 2003, the National Diabetes Education

Program (NDEP), funded by NIDDK and CDC,

launched the Small Steps, Big Rewards campaign

based on DPP results. DPP showed that a modest

weight loss and 30 minutes of exercise 5 days a

week reduced the risk of developing type 2 diabetes

and the complication of CVD in subjects who were

overweight, had impaired fasting glucose, and a family history of diabetes. NDEP is working with its

partners to develop materials for physicians and

patients based on the DPP lifestyle intervention. As

part of their campaign to put these tools to physicians and patients, they have established a Web site

(http://ndep.nih.gov). The Web site has links to and

now we will talking with partners in trying to get

those materials into the hands physicians and

patients. The website has inks to NHLBI and to the

Obesity Education Initiative that NHLBI helped

develop. NIDDK is also increasing its efforts with

regard to obesity research from trying to identify

new potential targets for therapy from molecular

research to clinical research related to prevention

and intervention.

NIDDK also is developing a school-based prevention

study for type 2 diabetes. Currently in its pilot

phase, the study will collect baseline data on height,

weight, waist circumference, blood pressure, glucose

tolerance testing, and lipids from students in middle

schools with at least 50 percent minority populations. Investigators will use the baseline data to

define metabolic outcome measures for the intervention, not just a weight loss outcome, for the clinical

trial. Dr. Fradkin said these pilot studies will provide a lot of population-based information about the

prevalence of the components of the metabolic syndrome in early adolescent children. She added that

she would be very interested to hear from other

groups about the metabolic syndrome in children,

including what definitions are being used, in order

to coordinate the outcome measures NIDDK is developing. This would likely make the results of the trial

more relevant to the syndrome as defined and used

by others.

Finally, NIDDK is talking with the National Center

on Health Statistics about potentially restoring the

oral glucose tolerance test (OGTT) to NHANES. She

explained that it was done this way in NHANES III

but when the yearly NHANES began, it was dropped,

largely to tie in with the ADA recommendations for

using fasting blood glucose to diagnose diabetes.

With the increasing prevalence of type 2 diabetes

and the DPP and other data related to the risk factors for CVD, the decision to use the 2-hour OGTT is

being reconsidered. Dr. Fradkin said the earliest the

change could happen would be in 2005, but she was

interested in the group’s opinion on how useful this

would be. Drs. Grundy and Haffner agreed this was

an interesting idea.

National Heart, Lung, and Blood Institute

Peter Savage, MD, Director, Division of

Epidemiology and Clinical Applications

Dr. Savage announced that NHLBI in collaboration

with the American Heart Association will conduct

two conferences on the metabolic syndrome, one in

April on the definitions and one in September on

treatment issues. Dr. Grundy will chair both meetings.

Dr. Savage presented opportunities for investigating

the metabolic syndrome through NHLBI-funded

cohort studies including the Framingham Original

Cohort and Framingham Offspring studies, the

Honolulu Heart Program, Atherosclerosis Risk in

Communities (ARIC),Cardiovascular Health Study

(CHS), and the and the Coronary Artery Risk

Development in Young Adults (CARDIA). Like NIDDK,

his Institute is not directly studying the metabolic
DMICC ANNUAL REPORT 110 FY 2003

syndrome but NHLBI does have studies related to it

and data sets that provide an opportunity to look at

questions, some of which had been discussed today.

CARDIA is a study of approximately 5,000 (5,115) 18-

to 30-year-old African American and white young

adults initially examined in 1985-86. Metabolic syndrome defined by ATP III was rare, about 4 percent.

Therefore, the investigators defined a pre-metabolic

syndrome to look at those who were above the gender-specific 90th percentile at the baseline exam for

three or more of the risk factors used by ATP III and

below the 10th percentile for HDL cholesterol.

The group was relatively unique in its balance by

race, sex, education, and age within centers. There

were five examinations over time with a substantial

followup. Seventy-four percent (74%) returned for the

Year 15 examination. What we found was that the

frequency of risk factors increased fairly strikingly

over the 15-year period in these young adults. The

prevalence of the syndrome rose from 4 percent at

baseline to 21 percent. It was highest in those at

year 15 who were already overweight at baseline

versus those who were normal at baseline, 41 percent versus 11 percent. Although all the group

gained some weight, the prevalence was higher in

those who gained 15 kilograms or more versus those

with little weight gain, 44 percent versus 25 percent.

Young adults with the pre-metabolic syndrome at

baseline were much more likely to have the fullblown ATP III syndrome at the end of 15 years. Now

the young adult years between ages 20 and 40 are

relatively silent years. Disease progresses during

that time, but the individuals tend to feel well and

do not have much in the way of symptomatic disease. These are people who are still healthy in young

adulthood and yet they are well on their way to

developing the abnormalities that are likely to lead

to clinical disease sometime in middle age or early

older years.

Dr. Savage next offered data sets available through

NHLBI to address some of the questions about the

metabolic syndrome. In addition to the cohort studies he listed at the beginning of this presentation,

Dr. Savage noted there is also data from current 

clinical trials (Asymptomatic Cardiac Ischemia Pilot

(ACIP); Intermittent Positive Pressure Breathing

(IPPB), Post-Coronary Artery Bypass Graft Study

(Post CABG), Thrombolysis in Myocardial Infarction

Study (TIMI II), Lung Health Study (LHS), Digitalis

Investigation Group (DIG), Beta Agonist in Mild

Asthma (BAGS), Antiarrthymics Versus Implantable

Defibrillators (AVID), and Colchicine in Moderate

Asthma (CIMA)). There is data on almost 50,000 

people who have had longitudinal exams, multiple

racial/ethnic groups, men and women, ages ranging

from about 18 to 100. Dr. Savage explained that

NHLBI is planning to gradually make more and 

more data from the large studies available.

Researchers may collaborate with existing study

investigators or request a public access data tape to

work on at their own pace. He pointed out that collaborating with the primary study investigators on

an issue as complex the metabolic syndrome has

many advantages such as the knowledge of the

investigator, the assistance in doing complex analyses provided by the statisticians of the coordinating

center, and access to the most recent data. The rights

of the primary investigators are protected by giving

those doing epidemiology studies a 5-year period

after the close of an examination and a 3-year period

after publication of the primary paper and the clinical trial. So for access to the most recent, complex

longitudinal data sets, it is important to try and

work with the study group. There are also a set of

rules to protect participant privacy and procedures

about what can and cannot be done with the data. To

obtain data sets directly from NHLBI, researchers

must agree to follow certain rules and procedures to

protect both the rights of the investigators and the

participants.

NHLBI’s Web site (www.nhlbi.nih.gov/resources/

deca/default.htm) provides data documentation, distribution agreement forms, information about

Institutional Review Board (IRB) approval, and the

overall policies that NHLBI has developed. The data

is provided at no cost to the applicant.
DMICC ANNUAL REPORT 111 FY 2003

Centers for Disease Control and Prevention

Frank Vinicor, MD, Director, Division of Diabetes

Translation

Dr. Vinicor stressed the importance of having science-based evidence before launching a public

health program as opposed to a clinical program

related to a disease or a syndrome. There is general

consensus that the 17 million persons diagnosed

with diabetes deserve treatment, not only for the

their glucose problem but for all the components

included in the metabolic syndrome definitions. In

NDEP and in other public health efforts, obesity,

cardiovascular risk factors, and so forth are

addressed. In taking a broad view of diabetes, however, CDC’s Division of Diabetes Translation is asking: When does the diabetes clock start ticking?

There is some question whether CDC should be

looking for the missing roughly 6 million people

with present but undiagnosed diabetes, an issue

that will have to be decided at the policymaking

level more than at the scientific level. Next, there is

a cohort of about 16 million persons who presumably have what is now called pre-diabetes. That

group is reasonably defined by IFG and/or IGT

based on several randomized controlled trials indicating that primary prevention should work and the

question is how to make it work. The fact that there

is good science underlying this gives us the moral,

ethical, and programmatic responsibility to take a

public health program forward. Those we call prediabetic presumably emanate out of the cohort of 45

million people identified in Dr. Earl Ford’s study as

having the metabolic syndrome as defined by ATP

III. Dr. Grundy indicated today that there are a lot of

people with metabolic syndrome who do develop

pre-diabetes and then diabetes. Finally, there is the

issue of the fetal programming mentioned by Dr.

Grave that may precede development or contribute

to the development of the metabolic syndrome.

Dr. Vinicor listed CDC’s public health activities as

involving basically three areas—surveillance activities, epidemiology and translation research, and

pubic health programs. As evidenced by Dr. Ford’s

surveillance work, CDC is using national data sets

to examine the prevalence and associated factors of

the cluster of conditions called the metabolic syndrome. The nature of the utility of these national

surveys varies. For example, the Behavioral Risk

Factor Surveillance Survey (BRFSS) is a self-report

so to the degree to which people do not know about

the syndrome, they cannot be asked “Have you ever

been told you have the metabolic syndrome?” There

is slightly better reliability in administrative data,

such as discharge data. Finally, NHANES, where the

components are actually measured, actually provides a sense of the prevalence of the factors associated with the metabolic syndrome. Surveillance is

typically not hypothesis driven.

Epidemiological and translation research is more

hypothesis generated. For example, the SEASRCH

study with CDC’s colleagues at NIDDK will hopefully identify people with type 2 diabetes and might be

an opportunity in a prospective way of looking at

whether or not elements of the metabolic syndrome

exist in this group. Similarly, Dr. Rodolfo Valdez who

was involved with the Bugalosa Heart Study in

Louisiana and Dr. Henry Kahn of CDC are looking at

ways to more easily define the metabolic syndrome

from a public health standpoint.

As a framework for public health programs, Dr.

Vinicor listed six progressive, interrelated steps

delineated by Dr. Detsky of Canada and his colleagues in 1990. The initial step is fundamental

research. Next is an efficacy trial, such as the DCCT,

followed by determining the intervention’s effectiveness, efficiency, availability, and distribution in the

real world—it works but at what financial cost, is it

affordable, are policies such as reimbursement in

place to allow to happen, and can it be distributed

in Small Town, Indiana, as well as in Bethesda,

Maryland. Dr. Savage reiterated that all these steps

are involved in thinking about what can be done

from a public health perspective to help people. He

said that, in his opinion, the field is at the fundamental research stage with regard to the metabolic

syndrome and cautioned against leaping over the

intervening steps between research and availability.

He felt it important to determine if it will make a
DMICC ANNUAL REPORT 112 FY 2003

real difference to identify persons with the syndrome rather than simply treating the individual

components, which no one would argue with as

being reasonable and necessary.

CDC is interested in participating in the fundamental research and through surveillance to understand

the syndrome better. The agency is not ready to

develop public health programs and policies based

on the metabolic syndrome. First, the case definition

needs to be clarified and examined by the nosology

experts to officially identify is as a syndrome.

Second, there needs to be more science-based evidence comparable to that from DCCT or DPP upon

which to build a public health perspective. Thirdly,

public health policy can not be determined by the

tails of the distribution curve; it appears to be a

heterogeneous condition, it is not clear how common

it is, and whereas unusual cases can determine a

clinical viewpoint, they cannot determine public

health policy. Finally, currently, CDC has many competing priorities. The Division’s mission is to help

people who have diabetes and now, for those with

pre-diabetes, to prevent diabetes. While the group is

interested intellectually, conceptually, and scientifically, there simply are no resources to deal with the

metabolic syndrome as a public health program.

Dr. Vinicor’s opinion was that “there is real gold 

out there” but the definition needs to be clarified

and a consensus reached on just what the metabolic

syndrome is. He saw value in finding a way to identify people at a younger age who might have or

develop the components and go on to develop 

diabetes or cardiovascular diseases, but the science

is not yet there from a CDC public health perspective. Dr. Vinicor emphasized once again that CDC is

interested from an investigative or scientific stance,

but his viewpoint is that it is a mistake to launch

public health programs unless there is solid science

behind them.

In the discussion that followed, Dr. Vinicor agreed

with Dr. Grundy that obesity is a public health concern. However, in studies with different racial/ethnic

populations, the sequence of events regarding obesity and hyperinsulinemia varies greatly. Therefore, he

believed it premature at this time to view obesity

together with the metabolic syndrome from a public

health point of view. NDEP is focusing its efforts on

that portion of the total obesity population that is

pre-diabetic, not a small group, some 16 to 18 million persons. Other programs at CDC and at NIH are

focusing on the broader obesity issues for the entire

population. The CDC Division of Diabetes Translation is part of that team but not taking the lead.

That is the role of a sister division.

American Association of Clinical

Endocrinologists (AACE)

Helena Rodbard, MD

Dr. Rodbard discussed the results of the American

College of Endocrinology (ACE) conference held in

the summer of 2002 and convened to address the

growing epidemic of the metabolic or insulin 

resistance syndrome. The conference’s consensus

statement will be published in the March issue of

Endocrine Practice. The previous year, ACE had

developed guidelines for treatment of type 2 diabetes with emphasis on the prevention of macrovascular disease and its comorbidities. The ACE Task

Force on the Insulin Resistance Syndrome was 

co-chaired by Dr. Daniel Einhorn and Dr. Gerald

Reaven. Dr. Earl Ford of CDC was also a member.

Dr. Rodbard said that ACE also championed development of the CPT code (277.7) for the metabolic

syndrome, which helped to put the syndrome on the

map, particularly for third-party payers and to legitimize the syndrome as a real clinical concern.

The first issue at the conference was what to call the

syndrome. Different names were proposed, such as

the metabolic syndrome, the dysmetabolic syndrome, and syndrome X. Finally, insulin resistance

syndrome was agreed on based on the rationale that

it was a more encompassing name and addressed

the pathophysiology of the disease. Diabetes, as Dr.

Grundy pointed out, previously was not part of this

syndrome, but was considered as another risk factor

for CHD. At the center of the equation as the main

concerns were heart disease and stroke. Although
DMICC ANNUAL REPORT 113 FY 2003

the vast majority of the people did not have diabetes, some of them actually would develop 

diabetes, as well as the other complications associated with CVD.

The components of the insulin resistance syndrome

as defined by ACE are a constellation of factors

including some degree of glucose intolerance,

although not overt diabetes; abnormal uric acid

metabolism; dyslipidemia, particularly with elevated

triglyceride levels, low HDL, high concentrations of

the small dense LDL, and the high lipidogenic particles; hemodynamic changes, with hypertension

being at the core of those; prothrombotic factors,

PAI-1 being one of them, and fibrinogen; markers of

inflammation, such as CRP, endothelial dysfunction,

and other markers of inflammation; polycystic ovary

syndrome (PCOS), a frequent concomitant of this

syndrome, and non-alcoholic fatty liver disease

(NASH). The concept is very emperic, but the main

concern is to decrease the incidence of CAD in the

population, primarily through lifestyle modifications

rather than pharmacological therapy.

Screening of people most likely to develop the

insulin resistance syndrome and be at high risk

would include those who have coronary heart disease, hypertension, PCOS, or acanthosis nigricans.

Dr. Rodbard said this latter symptom is particularly

important to clinicians as an indication of the 

syndrome that can be easily seen when the patient

walks into the room. Other indications are a family

history of type 2 diabetes, hypertension, or CVD;

women with a history of gestational diabetes or

individuals with glucose intolerance; ethnic minorities; people with sedentary lifestyles; a BMI greater

than 25 kg/m2; and age, particularly people over the

age of 40.

Particular hallmarks, the clinician would be looking

for as a definite for the diagnosis, would be triglyceride levels greater than 150 mg/dL, HDL cholesterol

less than 40 mg/dL in men and less than 50 mg/dL

in women, blood pressure greater than 130/85

mm/Hg, and fasting glucose between 110 and 126

mg/dL, people who would be candidates then for a

OGTT. A lesser factor, but one of the components,

would be increased microalbumin or urinary albumin excretion. Dr. Rodbard remarked that in

Renoir’s time, abdominal obesity might have been a

mark of beauty, but today concepts have changed.

We know that it is not healthy. She said it is incumbent on the leaders of medicine in the United States

to join forces and fight this growing epidemic..

In the discussion that followed, Dr. Rodbard

explained that the CPT code for the metabolic syndrome is a combination of mostly clinical criteria, a

combination of phenotypes, and some laboratory

tests as well. The CPT panel were not too specific.

The existence of a code was to make it implicit that

there is such a syndrome and there should be some

type of reimbursement for diagnosing and treating

it, because there is no reimbursement for obesity,

per se, unfortunately. Obviously, not everyone who is

obese has this syndrome, but if they have obesity

and they have some of the components of the syndrome, this code would be applicable.

Dr. Rodbard agreed with Dr. Vinicor that establishment of a code by the American Medical Association

CPT Editorial Panel does not guarantee reimbursement for screening or for treating something as a

syndrome by, for instance, the Centers for Medicaid

& Medicare Services (CMS).

Dr. Grundy suggested that when this metabolic 

condition is called the insulin resistance syndrome

and requires a glucose abnormality, it is likely to

lead to a focus on drug treatment of insulin resistance and treating persons with insulin-sensitizing

drugs prior to their developing diabetes. Also, it

would almost have to require glucose tolerance 

testing on a large number of people to make the

diagnosis. Who those people would be is another

issue—would it be just overweight people, or since

overweight is not a factor, would every patient be

tested as is commonly done now for cholesterol and

blood pressure?
DMICC ANNUAL REPORT 114 FY 2003

Dr. Rodbard replied that therapeutical approaches

will be the subject of a future conference. At this

time ACE was simply trying to identify people with

the syndrome because of concern for the coronary

risk factors and comorbidities associated with it.

The primary approach will probably be educating

the patients and encouraging them to be less sedentary, lose weight, do lifestyle modification, rather

than medical therapy. She said they did not have

much data to justify pharmacological therapy. It

would not make sense to putting everybody on TZDs

or another form of insulin-sensitizer without having

the data to show that would be effective.

American Diabetes Association

Richard Kahn, PhD

Dr. Kahn announced that ADA is in the midst, along

with some collaborators, in developing a paper on

the metabolic syndrome for publication in and ADA

journal and across,at least two or three other journals that reach different disciplines. The purpose of

the paper is to provide a perspective and address

questions such as “To what extent is the definition

of the metabolic syndrome based on data?” A number of components have been named by ATP III and

WHO and Dr. Rodbard added a few more from the

ACE definition. The issue, he said, is what is the

basis for choosing these components,. On what

basis are the cutpoints chosen? Are there data to

suggest that one cutpoint is better or worse than

another cutpoint for any of the components? How

does a risk factor become a part of the definition?

Why, for example, is not LDL or age a risk factor?

Age is as metabolic as blood pressure.

The second issue the paper will address is do all

combinations of the factors imbue the same risk?

Are the risks of adverse outcomes the same between

all ages, all races, and at all levels of any of the risk

factors? Dr. Kahn said this is important before

screening and treating a population based on the

syndrome.

The third major topic in the paper will be the etiology of the metabolic syndrome. Is it really all insulin

resistance or to what extent is it insulin resistance

versus something else. As Dr. Grundy pointed out,

there are different therapeutic ramifications

depending on what the underlying etiology is? Is

enough known yet to even say what the underlying

etiology is?

Last and most importantly, in Dr. Kahn’s opinion, is

what is the appropriate therapy for someone with

the metabolic syndrome? Is there any clinical evidence to support any therapy for the syndrome

itself—not hypertension, not diabetes, not dyslipidemia, but the general metabolic syndrome? Are

there any clinical studies that show CVD or diabetes

can be reduced by identifying someone with the

metabolic syndrome? The closest there is to that is

the results of the lifestyle interventions in the DPP

and the Finnish study, but they are not definitive for

the metabolic syndrome as defined.

Dr. Kahn stated that these questions important for

three reasons. First, the concept of a metabolic syndrome has grown from a very interesting, probably

important, epidemiological finding of clustering into

a disease in and of itself. As Dr. Rodbard pointed,

it has a treatment code and potentially could cost

billions of dollars in health care costs. Instead of

turning into a strategy to reduce obesity, it has

become a disease to be treated. Patients are not only

receiving pharmacological therapy , it has become 

a gold mine of insulin assays for laboratories and

referrals for specialists. The practitioner is unaware

of the uncertainties and problems regarding the

syndrome that are being discussed in this meeting.

Second, definitions tend to become cemented and are

very difficult to change even when new data arrives,

as ADA has experienced in the area of diabetes. It 

is critical not to define anything in a relatively arbitrary manner.

The third factor is the adding on of layer after layer

of things for physicians to do and for consumers to

do, which may divert attention from what may be

the most important things to do. For example, a

recent article in Diabetes Care, reported that only 3
DMICC ANNUAL REPORT 115 FY 2003

percent of diabetic patients treated by endocrinologists in an academic medical center were reaching

their hypertension, LDL , and hyperglycemia goals.

If additional items are added on, clinicians and consumers are likely to become more and more frustrated. Dr. Kahn’s recommendation was to “try to hold

the train back a little bit,” while continuing with

additional research.

Dr. Kahn’s comments elicited considerable discussion. Dr. Savage commented that there is not 

evidence that the metabolic syndrome is a disease

or that it should be treated in any specific way. On

the other hand, there is an epidemic of obesity in

the United States; millions of people are becoming

overweight, and data from the last 25 to 30 years

shows an alarming growth of obesity-related problems in children and young adults. There are many

questions to be examined. However, one relatively

clear message is that obese people are at markedly

increased risk of developing diabetes and at an

increased risk of developing heart disease. Therefore, the public and those delivering health care

need guidance to deal with the problem and prevent

the full-blown metabolic syndrome from developing

in large numbers of people.

Dr. Kahn responded that the conclusion that obesity

is a predominant, if not the most predominant, risk

factor, could have been reached 3 or 4 years ago. He

went on to say that organized medicine as it exists

today is not going to help the obesity problem,

because physicians by and large have no training

and no time to do what it takes and there are no

interventions that work in the long-term from the

medical perspective. In addition, there are billions

of dollars of marketing money favoring obesity. It is

possible to draw attention to obesity as a public

health problem, and this must be done, but what is

going to change the situation in the absence of a

pharmaceutical agent is really mass social reengineering.

Dr. Savage agreed that a cultural change was needed

before physicians could intervene in a way that

would change the problem in millions of people. He

added that people who gain a lot of weight, particularly during the years from 20 to 50, tend to be the

people who also have a much higher risk of developing multiple risk factors and the complications that

follow. This means that an attempt needs to be made

to promote a cultural change in the public that will

result in behavior changes. On the other hand, if

someone has full-blown risk factors, they need conventional medical therapy.

Dr. Spiegel said that one of the most compelling presentations he had heard was by Lawrence Green in

speaking of the smoking problem at a translation

session. Although the obesity challenge is even more

daunting, there are applicable comparisons to smoking, including the billions of marketing dollars targeted at the U.S. population and the fact that physicians alone cannot be the sole solution to the problem. A possible lesson can be learned from the

Surgeon General’s report on smoking and cancer

that was the impetus; it was clear cut. And even

though, the country is not “home free” and everything is not all solved and perfect—young women

are lighting up at increasing frequency—nonetheless, there has been a tremendous shift culturally.

Today’s stigma associated with smoking needs to be

avoided where obesity is concerned. Still, once there

is scientifically based data comparable to that of the

Surgeon General’s on smoking, then the public message can be that obesity is not a moral problem, it is

not a cosmetic problem, it is a health problem. Dr.

Spiegel stated that getting to the dimensions of it as

a health problem in the most rigorous, precise way

is what this discussion was really about.

Dr. Kahn agreed but drew attention to the fact that,

in spite of the intention to focus the issue on the

clusters of risk factors, or obesity’s relation to them,

the unintended consequence has been the rise of a

whole medical industry focusing on laboratory tests

and drugs at a time when the definitions are not

firm and the interventions are unclear. Although

there is a huge problem with obesity, the most

telling aspect is that if one looks at attendees at
DMICC ANNUAL REPORT 116 FY 2003

annual scientific sessions or any group of people

who should know about obesity, are they really any

different from the population at large?

Dr. Spiegel replied that there is a difference. If you

look at the behavioral risk factor surveys, there is 

a totally inverse correlation between education and

diabetes, particularly type 2 diabetes, and obesity.

There is a whole segment of the population that has

access to health clubs and so forth. The other thing

is that only a few decades ago, a significant number

of those present at a scientific gathering such as

this meeting would have been smoking. That no

longer happens. Eventually if the science is there

and the public health message is presented appropriately, substantial differences will be seen in 

overweight and obesity. That is not a Pollyanna

point of view.

Dr. Grundy added that when cardiovascular guidelines were being developed, similar criticisms were

voiced about definitions and other imperfections.

The same was true with cholesterol and blood pressure. His other point was that although there are

separate guidelines dealing with blood pressure and

cholesterol, patients tend to have the same cluster of

conditions—hypertension, dyslipidemia, and obesity.

In fact, there has been criticism for not unifying the

guidelines. The metabolic syndrome is a first

attempt to look at the whole patient and to recognize all the different components that make up the

constellation. It is a step in the direction of bringing

together and synthesizing a total risk package for

the patient.

Dr. Kahn raised another issue taken from the world

of diabetes. People have suggested that the 1997 definition for diabetes based on the so-called “gold

standard” of the OGTT as being 140 for IGT and 200

for diabetes should be changed based on current

data. The problem with doing that is that too many

papers have been written based on the old definition. As more and more people relate to the definition of the metabolic syndrome and base their

research and analyses on, for instance, the NCEP

definition, if data comes along demonstrating that a

cutpoint should be higher or lower or that a component should be added or subtracted, there will be a

point where people will say, “We can’t do that. It

would be too disruptive even if the data shows this

is not right or should be modified.” This is what

happened with the OGTT.

Dr. Haffner stated that changing from doing OGTTs

had some beneficial effects in identifying more

undiagnosed diabetic subjects. The use of the metabolic syndrome has not suggested new pharmacological therapy. It has suggested that there be a

focus on those risk factors for which there are

already guidelines. It also has focused on behavior.

The NCEP ATP II also recommended behavior modification, but the problem was that the behavioral

effects on LDL cholesterol were not that much, so

people wrote off the suggestion. The ATP III is being

taken more seriously. The definitions are probably

not perfect. More research is needed. There continues to be a need for standardization of insulin 

concentrations, which was agreed to 5 or 6 years

ago but has not happened. Interest in the metabolic

syndrome may stimulate that. One of the reasons

that people dislike the WHO definition is because

they do not know what insulin concentrations mean.

Dr. Kahn told the group that ADA has a committee

that will meet soon on standardizing the insulin

assay. He also pointed out that although the 

intentions of the ATP III definition were clear, the

consequence has been a growing number of pharmaceutical companies approaching ADA and fundamentally saying they want their drug, no matter

what it is, to be associated with the metabolic 

syndrome. Some companies have said they even do

not want their drug associated with lowering a 

particular parameter such as blood pressure or glucose or weight; they want it positioned as affecting

the metabolic syndrome.

Dr. Vinicor spoke of the power of science that was

experienced though the experience of DCCT. DCCT

created not just a medical change but a cultural

change in thinking about the importance of glucose

control. This power facilitated social-cultural
DMICC ANNUAL REPORT 117 FY 2003

change beyond the doctor’s office; it affected policymaking, Congressional appropriations, third-party

reimbursements, and the CMS. This is also true for

the DPP and the Finnish study. He urged that the

power of good science not be underestimated. If a

good study showed that addressing weight in 20-

year-olds in a rigorous way improved even intermediate outcomes in lipids and blood pressure after 5

years, that study could then change society.

Dr. Savage said that treating individual endpoints

would probably yield a slight incremental benefit,

but he felt that treating the metabolic syndrome

abnormalities as a whole would result in the most

benefit. It would be important to do an intervention

study in healthy young adults to see whether or not

there was a relatively cost-effective way of changing

the pattern of development of obesity and risk factors before they are clearly established, rather than

just continuing to document their prevalence in

more and more populations.

National Institute of Child Health and Human

Development (NICHD)

Gilman Grave, MD, Chief, Endocrinology,

Nutrition, and Growth Branch

Dr. Grave referred to the growing numbers of adolescents with type 2 diabetes, obesity, and high

blood pressure. NICHD is very interested in the

early origins of the clustering of these factors of the

metabolic syndrome and the heuristic value of looking at these in childhood, especially the fetal origins

of the syndrome. The NICHD National Children’s

Study will look at fetal origins of adult disease to

learn when it is first possible to detect the appearance of the cluster, to closely track it into adulthood, and to assess its implications. Referring to a

study by Dr. Boyd Metzger and the late Dr. Norbert

Freinkel, both of Northwestern University, Dr. Grave

noted that it will be interesting to see if study subjects who are now in their 20s and are the offspring

of women who had gestational diabetes show evidence of the clustering since the study showed earlier that the level of amniotic fluid insulin in their

mothers highly correlated with the incidence of the

children’s obesity at 10 years of age. NICHD also 

is very interested in the genotype-phenotype correlations and what the environmental interactions 

are because so many women with obesity do not

have this clustering.. He invited those present to

participate in an NICHD workshop on June 30-July

1 that will address the same questions presented

here: What is the etiology? What are the definitional

issues? What are the cutout points, especially by 

age in children? How does puberty affect insulin

resistance?

Food and Drug Administration

David Orloff, MD, Director, Division of Metabolic

and Endocrine Drug Products

In his presentation of FDA’s perspective on drug

development in the metabolic syndrome, Dr. Orloff

noted that the idea of the metabolic syndrome as a

target for therapy in and of itself has great appeal

to the pharmaceutical industry. He also stressed

that if the syndrome is to have public health implications, a consensus definition must first be established. While FDA shares the public health goals of

the other DMICC members, their mandate is sometimes incongruous in their duel role of protecting

the public health and also regulating and even promoting commerce in presumably safe and effective

drugs. FDA challenges sponsors to develop safe and

effective treatment and preventive agents, conducts

a guidance and review process and regulatory

actions to bring new drugs to market, and then partners in the public health arena to label the drugs or

treatment and preventive agents appropriately with

regard to expected risks and benefits. Dr. Orloff said

that expected risks and benefits is a very important

concept in drug labeling and to ensure “balanced

promotion.”

The agency’s current position on what would be

required for a “treatment for metabolic syndrome”

and a drug label is that diagnostic criteria is needed

that identifies a population in which negative outcomes attributable to the syndrome can be reliably

predicted. There would need to be a central pathogenetic mechanism or combination of mechanisms, a
DMICC ANNUAL REPORT 118 FY 2003

drug or combination of drugs impacting this mechanism that predictably ameliorates the spectrum of

metabolic and physiologic abnormalities of the syndrome, and finally evidence based on hard outcomes

of a role for drugs in the management of CVD or

another potentially mortal risk. Short of meeting

these criteria, FDA would say treat the components

of the syndrome, or without a consensus definition

of the syndrome, treat the known established cardiovascular risk factors for which there are effective

interventions as demonstrated by the impact on

intermediate or surrogate measures or evidence of

impact on overall hard outcomes. FDA agrees that

the metabolic syndrome comprises a constellation of

cardiovascular risk factors and that there is plentiful evidence suggesting these should be addressed

therapeutically. However, absent a unifying pathogenetic mechanism and evidence of a salutary effect

on outcomes of the intervention on that mechanism,

drug target(s) remain the components of the syndrome not the syndrome itself. Obesity interventions, such as lifestyle modification, that do not

involve drugs do not come under the purview of 

the FDA.

Dr. Grundy commented that one of his concerns has

been that in treating the components physicians

sometimes concentrate on one component and

ignore others. This is highlighted in patients with

diabetes where physicians may focus on treating

glucose because the patient has diabetes but fail to

treat the hypertension that almost all patients with

type 2 diabetes have, do not treat lipids appropriately, and do not recommend aspirin and things like

that. An advantage of looking at the syndrome is

that it considers all the components and points to

the need for each one requiring the appropriate

intervention, either drugs or not drugs.

Dr. Orloff agreed but said there is not universal

agreement on this at FDA. However, for a long time,

the agency has included in the labels for the lipidaltering drugs, the National Cholesterol Education

Program guidelines and information on multiple

risk factor intervention. Dr. Orloff proposed that

similar information could be provided on labels that

would be appropriate and applicable to patients

who have a constellation of cardiovascular risk 

factors, such as the components of the metabolic

syndrome. To include such directions in labeling,

the expected benefits of the intervention must be

specific and have been shown to impact a particular

outcome. Once that is well-established and a consensus reached on how to predict risk in patients

with a constellation of risk factors and how to guide

them therapeutically, then such information could

be included on labels.

Indian Health Service

Kelly Moore, MD, Clinical Specialty Consultant,

National Indian Health Service Diabetes Program

Dr. Moore reported that as a clinical care system,

IHS plans to provide training to its clinicians and

administrators on the metabolic syndrome and in

applying the additional funding received under the

special diabetes grant program for prevention and

treatment of diabetes in its patient population, the

agency will be looking at screening for diabetes and

for the metabolic syndrome. She said there is a

sense of the metabolic syndrome among IHS clinicians, and there have been a number of training sessions on the diagnostic criteria and on interventions

related to some of the components. Patients do not

have much knowledge of it.

Dr. Moore’s presentation focused on the risk factors

for the metabolic syndrome in the American Indian

and Alaska Native (AI/AN) population based on the

epidemiology of diabetes and obesity in this group,

particularly those who have diabetes but also AI/AN

youth at risk. IHS has developed state-by-state

maps, similar to CDC’s obesity maps, to show an

increasing age-adjusted prevalence of diagnosed

diabetes among AI/AN persons age 20 years and

older. Clearly there is an epidemic. The rate of high

prevalence in 1991 that existed in only four states—

Florida, Nebraska, Maine, and Mississippi—in 2001

existed in 18 states, Arizona, Colorado, Iowa,

Kansas, Maine, Michigan, Minnesota, Mississippi,

Montana, Nebraska, New Mexico, North Carolina,

North and South Dakota, Texas, Utah, Wisconsin,
DMICC ANNUAL REPORT 119 FY 2003

and Wyoming. Comparing prevalence in 1991 versus

2001 by age group shows alarming increases in the

younger age groups. There has been a 106 percent

increase in diagnosed diabetes in the 15- to 19-yearold adolescent population. There was also an

increase in prevalence of overweight and obesity

from 1994 through 2001 in the patient population

with diabetes. In a study of overweight AI youth

from a large tribe in the Southwest, children of 6

years of age are already well along the trajectory

towards developing diabetes (Elsenmann, 2000).

IHS does not have good data on the metabolic 

syndrome in AI/AN groups; their best data is from

the annual audit of the patient population with 

diabetes. The 2001 diabetes audit showed that nearly 40 percent of men and 30 percent of women under

the age of 45 who have diabetes were taking lipidlowering drugs. Over the age of 45, the percentage

increased to nearly 50 percent for men and a little

over 40 percent for women. There has been significant improvement in blood pressure control.

However, IHS is limited in data collection to patients

voluntarily seeking care so there is not any national

aggregate data on the general population. For example, there is very little data about men from age 20

to mid-40s because they do not often access the

health care system..

An intertribal heart project was reported by Kurt

Greenland et al. in Diabetes Care in 1999 that looked

at a cluster of risk factors associated with insulin

resistance including hypertension, diabetes, high

triglycerides, and low HDL, among three communities in Wisconsin and Minnesota. Prevalence estimates based on the study were approximately 10

percent for AI men and 6 percent for AI women.

Generally, the percentage of individuals with each

trait increased as the number of other syndrome

traits increased. In both men and women, the number of syndrome traits was related positively with

age and inversely with education level and unrelated

to their Native American ancestry.

A small study was conduced in the state of Montana

that screened youth from seven schools on two

reservations from 1999 through 2000. Fifty-five 

percent were from 6 to 11 years of age and 43 percent were 12 to 19 years of age. The majority of 

children were AI youth. In terms of risk factors for

diabetes among this population, 31 percent were

overweight, 33 percent had acanthosis nigricans,

and 61 percent had a family history of diabetes.

Compared to NHANES III data for youth in the same

age groups in the general U.S. population, the AI

youth had a 30-31 prevalence of overweight compared to the 13-14 percent of their U.S. counterparts.

Veterans Health Administration (VHA)

Thakor Patel, MD

Dr. Patel was unable to attend the meeting as

planned, but he submitted a set of slides that were

included in the participants’ program package. The

slides presented VHA clinical user demographics

and implications for the metabolic syndrome. Key

points were that the prevalence of the syndrome in

VHA is unknown, but data suggests that the prevalence is likely very high given the age of the clinical

population, which is increasing along with the

increasing number of minority groups. Diabetes

prevalence is increasing at younger ages in both

women and African Americans of both genders. In

fiscal year 1999, there was an overall prevalence of

diabetes of 16 percent, a 40.4 percent prevalence of

hypertension in the VA population as a whole, and a

65.6 percent rate of hypertension among patients

with diabetes. Veterans with diabetes also tend to

have numerous comorbidities and disabilities that

may limit lifestyle interventions.

Closing Remarks

Dr. Malozowski summarized the meeting by saying

that a consensus on a definition of the metabolic

syndrome was needed, there are many opportunities

to find answers to the questions raised at the meeting, some through mechanisms available at NIH, and

opportunities to pursue additional research in the

metabolic area. He thanked the participants and the

three speakers, and he thanked Dr. Savage for being

active in organizing the meeting.
DMICC ANNUAL REPORT 120 FY 2003

Dr. Spiegel also thanked the attendees and added

that there exists today an underlying vision of prevention and of change in the health care system

from being reactive to being proactive. This is a

major reason why groups are grappling with issues

like those discussed at this meeting, why more

research is needed, and why ultimately understanding of the genotype-phenotype correlation and geneenvironment interaction will be forthcoming.

Dr. Fradkin noted that all the major groups—NIDDK,

NHLBI, CDC, ADA, ACE, NCEP, NDEP—are presenting

basically the same message with regard to hypertension, hyperlipidemia, and hyperglycemia and the

prevention of cardiovascular disease and the complications of diabetes based on evidence from a

large number of clinical trials. In discussing the

metabolic syndrome, the consensus heard around

the table today was that the public is receiving a

very confusing picture. Each group has different

names for the syndrome and defines it differently.

Most importantly, there is not a research base to

know specifically what to do about the syndrome.

The most productive course of action at this point,

according to Dr. Fradkin, would be for the group to

define a research agenda related to the metabolic

syndrome and not get too far ahead of itself in

terms of a public health message. She emphasized

that it certainly had been very helpful for those

present to come together and share their perspectives.

The meeting was adjourned at 12:52 p.m.
DMICC ANNUAL REPORT 121 FY 2003

Participants

Richard Anderson, MD, PhD

Program Director, Division of Genetics 

and Developmental Biology

National Institute of General Medical Sciences

National Institutes of Health

Natcher Building, Room 2AS-25

45 Center Drive, MSC 6200

Bethesda, MD 20892

Phone: (301) 594-0943

Fax: (301) 480-2228

andersor@nigms.nih.gov

Nell Armstrong, PhD, RN

Program Director

National Institute of Nursing Research

National Institutes of Health

6701 Democracy Boulevard, Room 710

45 Center Drive, MSC 630

Bethesda, MD 20817

Phone: (301) 594-5973

Fax: (301) 480-8260

armstrongn@nih.gov

Perry Blackshear, MD, Dphil

Director, Office of Clinical Research

National Institute of Environmental Health Sciences

National Institutes of Health

PO Box 12233

NIEHS, MD A2-05

RTP, NC 27709

Phone: (919)-541-4899

Fax: (919) 541-4571

black009@niehs.nih.gov

Patricia Bryant, PhD

Director, Behavior and Social Science Research

Division of Population and Health 

Promotion Sciences

National Institute of Dental and 

Craniofacial Research

National Institutes of Health

Building 45, Room 4AS-43A

Bethesda, MD 20892

Phone: (301) 594-2095

Fax: (301) 480-8322

bryantp@de45.nidr.nih.gov

Joan Chamberlain

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

31 Center Drive

Building 31, Room 9A04

Bethesda, MD 20892

Phone: (301) 496-3583

Fax: (301) 496-7422

ChamberlainJ@extra.niddk.nih.gov

Michelle Cissell, PhD

AAAS/NIH Science Policy Fellow

Office of Scientific Program and Policy Analysis

National Institute of Diabetes and 

Digestive and Kidney Diseases 

National Institutes of Health

31 Center Drive

Building 31, Room 9A05

Bethesda, MD 20892

Phone: (301) 496-6623

Fax: (301) 480-6741 

cissellm@extra.niddk.nih.gov
DMICC ANNUAL REPORT 122 FY 2003

James Cleeman, MD

Coordinator, National Cholesterol 

Education Program

National Heart, Lung and Blood Institute

National Institutes of Health

Building 31, Room 4A16

Bethesda, MD 20892

jc79f@NIH.GOV

Peggy R. Coleman, RN, MS

Operations Manager for the Health 

Disparities Collaboratives

Health Resources and Services Administration

Department of Health and Human Services

Building 7-8D4 EWT

Bethesda, MD 20814

Phone: (301) 594-4300

Fax: (301) 594-4997

PColeman@hrsa.gov

Chhanda Dutta, PhD

Chief, Clinical Gerontology Branch

Geriatrics and Clinical Gerontology Program

National Institute on Aging

National Institutes of Health

Gateway Building, Suite 3C-307

7201 Wisconsin Avenue

Bethesda, MD 20892

Phone: (301) 435-3048

Fax: (301) 402-1784

cd23z@nih.gov

Mark Eberhardt, PhD

Epidemiologist

National Center for Health Statistics

Centers for Disease Control and Prevention

3311 Toledo Road

Hyattsville, MD 20782

Phone: (301) 436-5979, ext. 142

Fax: (301) 436-8459

mse1@cdc.gov

Jean Flagg-Newton, MD

Chief, Office of Research

National Center on Minority Health 

and Health Disparities

National Institutes of Health

2 Democracy Plaza

6707 Democracy Boulevard, Suite 800

Bethesda, MD 20892

Phone: (301) 402-1366

Fax: (301) 402-7040

flaggnej@od.nih.gov

Earl Ford, MD

Centers for Disease Control and Prevention

4770 Buford Highway, NW MSK-10

Atlanta, GA 30341

esf2@cdc.gov

Joanne Gallivan 

Director, National Diabetes Education Program

National Diabetes Education Program

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

31 Center Drive

Building 31, Room 9a04

Bethesda, MD 20892

Phone: (301) 496-6110

Fax: (301) 496-7422

joanne_gallivan@nih.gov

Lisa Gansheroff, PhD

Office of Scientific Program and Policy Analysis

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

Building 31, Room 9A05

9000 Rockville Pike, MSC 2560

Bethesda, MD 20892

Phone: (301) 496-6623

Fax: (301) 480-6741

gansheroffl@extra.niddk.nih.gov
DMICC ANNUAL REPORT 123 FY 2003

Sanford Garfield, PhD

Senior Advisor, Biometrics and Behavioral Science

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

6707 Democracy Boulevard, Room 685

Bethesda, MD 20892

Phone: (301) 594-8803

Fax: (301) 480-3503

garfields@extra.niddk.nih.gov

Joan T. Harmon, PhD

Director, Division of Bioengineering

National Institute of Biomedical 

Imaging and Bioengineering

National Institutes of Health

6707 Democracy Boulevard, Room 241

Bethesda, MD 20892

Phone: (301) 451-4776

Fax: (301) 480-4515

harmonj@mail.nih.gov

Ann A. Jerkins, PhD

Scientific Review Administrator

Metabolism Study Section

Center for Scientific Review

National Institutes of Health

Nutritional and Metabolic Sciences IRG

6701 Rockledge Drive, Rm. 6154 (MSC 7892)

Bethesda, MD 20892

Phone: (301) 435-4514

Fax: (301) 480-2065

jerkinsa@csr.nih.gov

Henry Kahn, MD 

Centers for Disease Control and Prevention

4770 Buford Highway, NW MSK-10

Atlanta, GA 30341

hsk1@cdc.gov

Jane Kelly, MD

Director, National Diabetes Education Program

Division of Diabetes Translation

Centers for Disease Control and Prevention

Mailstop K-10

4770 Buford Highway

Atlanta, GA 30341

Phone: (770) 488-5196

Fax: (770) 488-5195

jkelly@cdc.gov

Jag L. Khalsa, PhD

Pharmacologist/Health Scientist Administrator

Center on AIDS and other Medical 

Consequences of Drug Abuse (CAMCODA)

National Institute on Drug Abuse

National Institute of Health

6001 Executive Boulevard, Room 5098, MSC 9593

Bethesda, MD 20892

Phone: (301) 443-1801

Fax: (301) 954-6566

jk98p@nih.gov

Richard Knazek, MD

Medical Officer

National Center for Research Resources

National Institutes of Health

6705 Rockledge Drive

Rockledge One, Room 6128

Bethesda, MD 20892

Phone: (301) 435-0790

Fax: (301) 480-3661

richardk@ncrr.nih.gov

Kathy Kranzfelder 

National Institute of Diabetes and Digestive and

Kidney Diseases

National Institutes of Health

31 Center Drive

Building 31, Room 9A04

Bethesda, MD 20892

Phone: (301) 496-3583

Fax: (301) 496-7422

kranzfeldk@hq.niddk.nih.gov
DMICC ANNUAL REPORT 124 FY 2003

Saul Malozowski, MD, PhD, MBA

Senior Advisor for Clinical Trials and 

Diabetes Translation

Division of Diabetes, Endocrinology,

and Metabolic Diseases 

National Institute of Diabetes and Digestive and

Kidney Diseases 

National Institutes of Health

6707 Democracy Boulevard, Room 679, MSC5460 

Bethesda MD 20892 

Phone: (301) 451-4683

Fax: (301) 480-3503 

sm87j@nih.gov

John Ridge, MD

Program Officer

Diabetes and Autoimmunity Section of 

the Clinical Immunology Branch

National Institute of Allergy and Infectious Diseases

National Institutes of Health

6700B Rockledge Drive

9000 Rockville Pike

Bethesda, MD 20892

Phone: (301) 496-7104

Fax: (301) 402-2571

jr34g@nih.gov

Ed Roccella, MD

Coordinator, National High Blood 

Pressure Education Program

National Heart, Lung and Blood Institute

Building 31, Room 4A18

Bethesda, MD 20892

roccelle@nhlbi.nih.gov

David Rodbard, MD

Managing Research Scientist/Managing Director

American Institutes for Research

1000 Thomas Jefferson Street, N.W.

Washington DC 20007

Phone: (202) 342-5130

Fax: (202) 342-5033

drodbard@air.org

Elizabeth Singer

Director, Office of Communications 

and Public Liaison

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

31 Center Drive

Building 31, Room 9A04

Bethesda, MD 20892

Phone: (301) 496-3583

Fax: (301) 496-7422 

singerb@extra.niddk.nih.gov

Allen Spiegel, MD

Director

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

Building 31, Room 9A52

31 Center Drive, MSC 2560

Bethesda, MD 20892

Phone: (301) 496-5877

Fax: (301) 402-2125

spiegela@extra.niddk.nih.gov

David Stevens, MD, FAAFP

Acting Chief, Clinical Quality 

Improvement Branch

Division of Clinical Quality

Bureau of Primary Health Care

Health Resources and Services Administration

4350 East West Highway, 7th Floor

Bethesda, MD 20814

Phone: (301) 594-4323

Fax: (301) 594-4997

dstevens@hrsa.gov

Elizabeth Warren-Boulton, RN, MSN, CDE

Hager Sharp, Inc.

Phone: (202) 966-4150

elizawb@aol.com
DMICC ANNUAL REPORT 125 FY 2003

John Whitaker

National Eye Institute

National Institutes of Health

31 Center Drive

Building 31, Room 6A25

Bethesda, MD 20892

Phone: (301) 496-4308

Fax: (301) 402-3799

john.whitaker@nei.nih.gov

Violet Woo, MS, MPH

Program Analyst

Office of Minority Health

Department of Health and Human Services

5515 Security Lane, Suite 1000

Rockville, MD 20852

Phone: (301) 443-9923

Fax: (301) 443-8280

vwoo@osophs.dhhs.gov
DMICC ANNUAL REPORT 127 FY 2003

Speakers

Judith E. Fradkin, MD

Director, Division of Diabetes, Endocrinology 

and Metabolic Diseases

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

Building 31, Room 9A27

31 Center Drive, MSC 2560

Bethesda, MD 20892

Phone: (301) 496-7349

Fax: (301) 480-6792

jf58s@nih.gov

Gilman D. Grave, MD

Chief, Endocrinology, Nutrition 

and Growth Branch

Center for Research for Mothers and Children

National Institute of Child Health 

and Human Development

National Institutes of Health

6100 Executive Boulevard; Suite 4B-11 

Bethesda, MD 20892-7510

Phone: (301) 496-5593

Fax: (301) 480-9791

gg37v@nih.gov

Scott M. Grundy, M.D., Ph.D.

Health Science Center

Human Nutrition Center

University of Texas

5323 Harry Hines Boulevard

Dallas, TX 75390

Phone: (214) 648-2890

Fax: (214) 648-4837

scott.grundy@utsouthwestern.edu

Steve M. Haffner, M.D.

Department of Medicine/Clinical Epidemiology

University of Texas Health Center

7703 Floyd Curl Drive

San Antonio, TX 78229 

Phone: (210) 567-4722

Fax: (210) 567-6955

haffner@uthscsa.edu

Richard Khan, PhD

American Diabetes Association

1701 North Beauregard Street

Alexandria, VA 22311

rkhan@diabetes.org

James B. Meigs, M.D., MPH

General Internal Medicine Unit

Massachusetts General Hospital

15 Parkman Street, WAC 645

Boston, MA 02114

Phone: (617) 724-3203

Fax: (617) 724-3544

jmeigs@partners.org

Kelly R. Moore, MD

Clinical Specialty Consultant 

National Indian Health Service 

Diabetes Program 

5300 Homestead Road NE 

Albuquerque, NM 87110 

Phone: (505) 248-4811 or 4182 

Fax: (505) 248-4188 

kelly.moore@mail.ihs.gov

David Orloff, MD

Director, Division of Metabolic and 

Endocrine Drug Products

Food and Drug Administration

Parklawn Building, Room 14B-45

5600 Fishers Lane

Rockville, MD 20857

Phone: (301) 827-6430

Fax::(301) 443-9282

Email: orloffd@cder.fda.gov

T.G.Patel, MD, MACP 

Veterans Health Administration

810 Vermont Av.

Washington, DC 20420

Phone: (202)-273-8490 

Fax: (202) 273-9142 

tgpatel@hq.med.va.gov
DMICC ANNUAL REPORT 128 FY 2003

Helena Rodband, MD, FACE

American Association of Clinical 

Endocrinologists

hrodbard@erols.com

Peter J. Savage, MD

Director, Division of Epidemiology 

and Clinical Applications

National, Heart, Lung and Blood Institute

National Institutes of Health

Rockledge 2, Room 8104

Bethesda, MD 20817

Phone: (301) 435-0421

Fax: (301) 480-1864

Email: savagep@nhlbi.nih.gov

Frank Vinicor, MD

Director, Division of Diabetes Translation

Centers for Disease Control and Prevention

4770 Buford Highway, North East, MSK-10

Atlanta, GA 30341

Phone: (770) 488-5000

Fax: (770) 488-5966

Email: fxv1@cdc.gov
DMICC ANNUAL REPORT 129 FY 2003

DIABETES MELLITUS INTERAGENCY 

COORDINATING COMMITTEE MEETING 

Lister Hill Auditorium, NIH Campus

Bethesda, Maryland

April 11, 2003

SUMMARY MINUTES

Dr. Judith E. Fradkin, Director, Division of Diabetes,

Endocrinology, and Metabolic Diseases, National

Institute of Diabetes and Digestive and Kidney

Diseases (NIDDK), opened the session by thanking

the speakers and attendees for their participation in

the 20th anniversary symposium of the Diabetes

Control and Complications Trial (DCCT) and the

Epidemiology of Diabetes Interventions and

Complications (EDIC) Study to which the DMICC

meeting was appended. Dr. Fradkin then reiterated

the conference goals of the DCCT/EDIC symposium,

held April 10–11 and entitled “Metabolic Imprinting

and the Long-Term Complications of Diabetes

Mellitus: Bench to Bedside and Back”:

• To celebrate and commemorate the accomplishments of the DCCT/EDIC on its 20th anniversary;

• To explore the possible mechanistic basis for what

has been tentatively termed "metabolic memory"

or "imprinting"; and

• To generate plans for the fostering of research in

developing new therapies for the complications of

type 1 diabetes.

Dr. Fradkin explained to the guests present that the

DMICC is a forum for the coordination of diabetes

research and healthcare aspects across multiple

institutes and centers at the National Institutes of

Health (NIH), other agencies within the U.S.

Department of Health and Human Services (DHHS),

and beyond.

Special funding for type 1 diabetes research began

in 1998, with a $30 million annual budget, and has

increased to five times that amount, $150 million per

year, for FY 2004-2008, providing a total funding of

$1.14 billion over the course of its legislative history

(Balanced Budget Act of 1997, P.L. 105–33, amended

by FY 2001 Consolidated Appropriations Act, P.L.

106–554). Since its inception, this funding has been

the source of a number of initiatives, such as the

establishment of genetic consortia including a

genetic collection being carried out by the EDIC

study group. DCCT/EDIC has provided a very wellcharacterized group of patients in terms of meta

bolic control for examination of the potential genetic

factors that might influence the risk of complications. Other initiatives relevant to complications

pursued with the special funds include the Animal

Models of Diabetic Complications Consortium

(AMDCC), the macular edema clinical research 

consortia, initiatives for the development of surrogate markers for diabetes complications, and pilot

studies for the development of new therapies.

Of particular emphasis has been the funding of

studies fostering bench-to-bedside research. Dr.

Fradkin stressed that development of partnerships

between individuals working in type 1 diabetes with

experts from outside the field, such as some of those

who were very much a part of the current DCCT/

EDIC conference, is an area that will aid in the

exploration and examination of new directions for

diabetes research.

In May 2002, an Advisory Panel recommended

expanding the areas of opportunity for type 1 
DMICC ANNUAL REPORT 130 FY 2003

diabetes research to include research in inflammation and vascular disease complications,

development of improved animal models, expanded

clinical research, and the application of new technologies. They further recognized that available

resources and infrastructure can be enhanced by 

the development of consortia to examine multiple

complications and the fostering of partnerships

between researchers in academia, Government, and

industry. Preclinical development of therapeutic

applications and a central knowledge base of complications-related initiatives were also recommended. Dr. Fradkin said a Web site will be developed 

to identify opportunities using type 1 funds in

response to these recommendations and to

announce the availability of resources resulting

from such initiatives.

To capitalize on what was presented during the

DCCT/EDIC conference and to focus future fundamental research on potential opportunities and 

initiatives recommended by conference participants,

Dr. Fradkin outlined several key questions concerning the pathogenesis, prevention, and therapy of

complications and invited speakers to respond 

with specific recommendations. The following 

sections summarize their presentations and the

attendees’ comments.

What Are the Major Gaps in Our Knowledge of

the Pathogenesis and Therapy of Vascular

Complications?

Dr. David M. Nathan, Professor of Medicine, Harvard

Medical School and Massachusetts General Hospital, Boston, summarized the following lessons

learned from DCCT/EDIC that were presented 

during the symposium and outlined opportunities

for future research:

• Glycemia is clearly the predominant mediator of

the effects of intensive versus conventional therapy, explaining more than 95 percent of the effect

of intensive therapy.

• Despite the subsequent narrowing of glycemia 

levels, the differences in outcomes between the

original intensive and conventional therapy

groups persist.

• The persistent difference in diabetic complications, potentially mediated by long-term beneficial

effects of lower glycemia and/or persistent

adverse effects of hyperglycemia, appears to 

be maintained for as long as 8 years after the 

separation in glycemia has dissipated, a phenomenon currently termed "imprinting" or 

"metabolic memory.

• One of the major and most interesting observations from DCCT was the demonstration that it is

the original separation in glycemia level that

accounts for most of the original effect.

• Glycemic levels and the changes mediated by

intensive therapy may play a role in the development of macrovascular disease, as well as

microvascular disease.

• Recent data with regard to calcification in the

heart appear to demonstrate a difference between

intensive and conventional groups.

During the DCCT/EDIC conference, several pathophysiologic mechanisms were presented to explain

the effects of glycemic control and other currently

used interventions on diabetic micro- and macrovascular complications, including glycation, inflammation, glycoxidation, apoptosis, lipoxidation, cellular

issues, oxidation, and genetics/epigenetics.

Investigators from diverse backgrounds explored

several of these potential mechanisms that might

explain the imprinting effects or metabolic memory

from the early intensive glycemic control on longterm complications, including glycation/receptors

for advanced glycation endproducts (RAGE), genetics/epigenetics, cellular/vascular/angiogenesis

issues, and immunologic factors. Topics addressed

during the conference included:
DMICC ANNUAL REPORT 131 FY 2003

• Imprinting in DCCT/EDIC.

• Pathophysiology of diabetic complications.

• Potential mechanisms for long-term effects.

• Animal models and data regarding micro- and

macrovascular disease.

• New methods of detecting and tracking complications that may be useful in clinical trials.

• Results of clinical trials directed at a number 

of factors that may be operant in diabetic 

complications.

Dr. Nathan also mentioned several topics that were

not discussed, but which might have been considered within the scope of the conference, such as the

limitations in achieving long-term control of hyperglycemia with currently available therapy; the ways

of improving glucose control in type 1 diabetes,

either by biological or mechanical approaches to

maintain normal glycemia; and the prevention or

cure of type 1 diabetes.

A significant outcome of the symposium was the

identification of several areas for additional

research. First, a consensus must be reached regarding reliable, practical biomarkers or surrogates for

cardiovascular disease, so that meaningful comparisons can be made in clinical trials between the

effects of different interventions. Doing so will ultimately result in clarification of what sometimes

appear to be contradictory results in studies and

will allow for greater efficiency in the performance

of interventional studies. Second, a better understanding is needed of the differences and 

similarities in the effects of glycemic and other

interventions on different end organs, as well as 

the influence of genetic factors in this regard.

Dr. Nathan emphasized that the DCCT/EDIC group is

the most vigorously and thoroughly studied population of type 1 diabetic patients in history, with 95

percent retention of subjects over a span of 20 years

(n=1385/1441), and with an average follow-up of

approximately 16 years. The population has been

extensively characterized and phenotyped over time

with regard to complications, diabetes therapy and

chronic glycemia, and established and potential risk

factors, and it has provided researchers with an

incredibly valuable resource of stored biological

specimens, including DNA, which can be well utilized for the validation of biomarkers.

Dr. Nathan suggested that the DCCT/EDIC group

continue to examine the relationship between the

panoply of risk factors and macrovascular disease

and the more severe stages of microvascular disease.

As the DCCT/EDIC population evolves and develops

more advanced eye, kidney, and macrovascular disease, investigators will be able to study the effects

of established and putative risk factors on these

clinically onerous complications. Diabetes

researchers should also continue to study and to

define the imprinting phenomenon described during

the DCCT/EDIC symposium, including expanding

epidemiologic approaches currently in use and

through case-control studies.

DCCT/EDIC data can be used to identify and define

clinically relevant biomarkers of complications that

may be used in future studies, using phenotypic data

and stored samples, which may also be used to identify biochemical steps in the pathogenesis of complications. Finally, the current DCCT/EDIC genetic initiative that is looking at the genetic contribution to

susceptibility for developing complications ought to

be continued.

Dr. Saul Genuth, Professor of Medicine, Division of

Clinical and Molecular Endocrinology, Case Western

Reserve University, added that the DCCT/EDIC

cohort is not only the most vigorously and consistently studied group of type 1 diabetics, but that it

is also the most accurately studied group, producing

high quality data as a result of good quality control

measures. Dr. Genuth stressed the importance of and

opportunity for lifelong follow-up by NIH, given the

high level of commitment of the patient participants

in the cohort, due in part to the research mindset of
DMICC ANNUAL REPORT 132 FY 2003

the patients and to the personal bonding between

patients and study investigators. He recommended

that researchers capitalize on the strong research

motivation of the cohort patients in their consideration of future studies and initiatives.

During the discussion following Dr. Nathan's 

presentation, Dr. Michael Brownlee, Anita and Jack

Saltz Professor of Diabetes Research, Department of

Medicine, Albert Einstein College of Medicine,

Bronx, New York, pointed out a further knowledge

gap with regard to the adverse effects of acute

hyperglycemia or stress hyperglycemia. Data suggest

that coronary disease is largely a metabolic disease;

in treatment of individuals with stress hyperglycemia, the outcome in the area of infarction in the

brain is proportional to the level of hyperglycemia

on admission. Seventy percent of those who have

myocardial infarctions are either diagnosed diabetics or people with impaired glucose tolerance. A better understanding of the mechanisms of the disease

will aid in the prevention of damaging effects on

outcomes, especially since the events typically measured in the diabetic population are ultimately fatal.

During the discussion following Dr. Nathan's presentation, Dr. Michael Brownlee, Anita and Jack Saltz

Professor of Diabetes Research, Department of

Medicine, Albert Einstein College of Medicine,

Bronx, New York, pointed out a further knowledge

gap with regard to the adverse effects of acute

hyperglycemia or stress hyperglycemia. In addition

to recent data showing that the majority of patients

with coronary artery disease are either diabetic 

or have impaired glucose tolerance, acute hyperglycemia has been shown to adversely affect the 

outcome of myocardial infarction and stroke. The

area of infarction in the brain is proportional to the

level of hyperglycemia on admission. Seventy percent of those who have myocardial infarctions are

either diagnosed diabetics or people with impaired

glucose tolerance.

Dr. Mark E. Cooper, Director, Baker Heart Research

Institute, Melbourne, Australia, stressed that the

development of macrovascular complications from

diabetes will prove to be especially important over

the next 10 years for the DCCT/EDIC population.

Why some diabetic individuals are less able to 

withstand a given load of macrovascular disease

than their non-diabetic counterparts is an area of

research that may be further examined with data

from the DCCT/EDIC cohort, since baseline data

such as echocardiography is available for these

patients. Advanced echocardiography allows 

diastolic dysfunction—which may be linked to 

the mechanisms reviewed during the DCCT/EDIC

symposium—to be more easily discernible and 

more accurately diagnosed. Dr. Genuth added that

the DCCT/EDIC patient population is exceptionally

receptive to further testing or exams, especially

where heart function is concerned, stating that 

85 percent have already had coronary calcium 

scans performed.

Dr. Peter Savage, Director, Division of Epidemiology

and Clinical Applications, National Heart, Lung, and

Blood Institute (NHLBI), offered three points that

bear closer scrutiny: (1) the subclinical cardiac dysfunction known to occur in diabetics; (2) the amount

of vascular disease prior to and following the onset

of renal disease and the association of renal disease

with the exacerbation or progression of atherosclerosis; and (3) the importance of more efficient clinical trials to examine the means for and to document

the correlate between subclinical disease measures

and events, particularly in light of the new and multiple interventions available. As an example, Dr.

Savage suggested that abnormalities in the system

might add substantially to the subclinical disease; if

not, then the subclinical disease could be used as a

predictor.

Dr. David R. Matthews, Professor of Diabetic

Medicine, Oxford Centre for Diabetes Endocrinology

and Metabolism, England, observed that perhaps

part of the "imprinting" in the DCCT/EDIC cohort is

due to the education of and attention given to the

patient participants.

Dr. John W. Baynes, Carolina Distinguished

Professor, Department of Chemistry and
DMICC ANNUAL REPORT 133 FY 2003

Biochemistry, University of South Carolina,

Columbia, cautioned that the group not become too

glucocentric. While glucose might turn out to be a

statistically important mediator, understanding the

downstream effects is also critical. Dr. Baynes suggested that a greater emphasis be placed on insulin

resistance in pre-diabetic states, which often precede the development of type 2 diabetes, during

which time substantial damage can occur. Dr. Helen

Vlassara, Director, Division of Experimental Diabetes

and Aging, Mount Sinai School of Medicine, New

York, added that researchers ought not to ignore

derivatives of glucose metabolism.

The area of implementation and dissemination

research, also termed translational research, was an

area not covered by the symposium, but one which

Dr. Denise Simons-Morton, Acting Director, Clinical

Applications and Prevention, Division of

Epidemiology and Clinical Applications, NHLBI,

brought to the attention of the group. It was suggested by Dr. Daniel Stryer, Acting Director, Center

for Quality Improvement and Patient Safety, Agency

for Healthcare Research and Quality (AHRQ), that

banked clinical data studies could also be supported

by R03 or hyper-accelerated grant applications, and

that these data could provide information on general

markers of inflammation.

Dr. John M. Lachin, Professor of Biostatistics and

Epidemiology, The Biostatistics Center, George

Washington University, Rockville, Maryland, offered

the idea that a future challenge for researchers will

be the characterization of lesions at the cellular

level, which would represent the true factors that

are determining the risk of further disease progression or the risk of complications.

How Can We Foster Development of Animal

Models in Which Potential New Therapies Can 

be Explored?

Dr. Timothy S. Kern, Director, Center for Diabetes

Research, Case Western Reserve University,

Cleveland, addressed the issues of animal models in

type 1 diabetes research. Although most purely diabetic animal models do not progress to advanced

stages, they nonetheless provide valuable information, including biochemical abnormalities that seem

to play a role in the development of various forms 

of pathology.

Areas that warrant further attention and 

research include:

• Establishment of the validity of animal models,

given that they largely tend to develop the early

lesions, but fail to progress.

• Use of animal models in the development and validation of surrogate markers.

• Examination of genetic contributions to complications, since animal models offer a unique opportunity in terms of cross-breeding.

• Understanding the clonal basis or "imprinting"

basis of "metabolic memory."

Considering how long complications take to develop

in humans, barriers exist in the use of animal 

models in diabetes research on complications

because the animals have relatively short lifespans.

A further obstacle is the lack of macular edema

models and the inability of researchers to make specialized measurements. However, the latter difficulty

might be overcome through the use of core facilities

to provide measurement services.

Dr. Kern encouraged the establishment of a group

that would evaluate therapies and decide methods

for moving therapies into the clinical setting. He

also suggested expansion of the consortium on 

animal models to provide an arena for discussion

beyond the grant recipients and broaden the scope

of researchers, a suggestion echoed by several participants at the symposium.

Dr. Cooper expressed concern that appropriate animal models be used. Since the consortium is trying

to generate new animal models, they might consider

starting with animals such as the db/db mice, which

have fewer complications that will affect study 
DMICC ANNUAL REPORT 134 FY 2003

results. Drs. Kern and Vlassara agreed with this

comment, and Dr. Vlassara further challenged the

definition of what constitutes a normal animal

model or normal baseline. She suggested a new

"hyperglycotoxemic" model be developed.

Dr. Eva L. Feldman, Professor of Neurology,

University of Michigan, Ann Arbor, shared information from the AMDCC. The consortium has moved

from having 2 animal models to 12 models and is

now gathering interesting data on atherosclerotic

and nephropathic models. The large bioinformation

component of the consortium has allowed for a generous amount of shared data.

Dr. Fradkin suggested that further comments regarding expansion of the consortium be directed to Dr.

Robert Star, Senior Scientific Advisor, NIDDK, at

Robert_Star@nih.gov.

How Can We Foster Development of Surrogate

Markers Useful for Clinical Trials of Potential 

New Therapies?

Dr. Ann Marie Schmidt, Associate Professor and

Chief, Division of Surgical Science, College of

Physicians and Surgeons, Columbia University,

New York, categorized cardiovascular disease and

diabetes into three parts: (1) the innate cardiac dysfunction; (2) surrogate endpoints for long-term 

vascular disease, including stenting and the amount

of neointimal expansion as a potential surrogate

endpoint, given that diabetic individuals undergoing

angioplasty and revascularization procedures do

very poorly; and (3) macrovascular disease and atherosclerosis itself. (Dr. Schmidt served on the May

16, 2002, Advisory Panel.)

Dr. Schmidt proposed that intravascular ultrasonography (IVUS) might also be used as an endpoint.

Since the increase in IVUS quantification of

macrovascular disease has been demonstrated, it

appears that the Food and Drug Administration

(FDA) might be softening with respect to endpoints

other than death and clinical events.

With regard to plaque and instability, examination

of the inflammatory mediators and inflammatory

markers produced by peripheral monocytes in

humans following intervention may provide a useful

surrogate marker. MMP9, antigen activity, and procoagulant response are also being investigated, as

well as impaired endothelial independent relaxation,

although the last is not an FDA-approved endpoint.

The response to acetylcholine is very abnormal in

diabetic individuals and can in and of itself be a

surrogate marker.

Clearly, a very important surrogate marker is C-reactive protein (CRP), which might prove useful not only

with regard to defining response to therapy, but also

when examining quartiles of elevated CRP levels at

baseline and their application to relative risk.

Dr. Schmidt identified the following methods for

development of surrogate markers:

• Functional MRI is a promising study method,

particularly because of its wide availability, but

one which may require incentives to encourage

study participation.

• Urine protocytes may be a potential marker of

early injury, although albuminuria is not an FDAapproved endpoint.

• Degree of alveolar bone loss and periodontal disease are potential surrogate markers for inflammatory baseline and response, since epidemiological

data suggest that periodontal disease, regardless

of the presence or absence of diabetes, is a risk

factor for the development of atherosclerosis.
DMICC ANNUAL REPORT 135 FY 2003

• Erectile dysfunction, because it involves not only

neurology but also vasculature, is a possible 

surrogate marker.

• Skin biopsies could be surrogate markers for levels

of collagen abnormalities.

• Live oxidation products are possible surrogate

markers for measurement.

Information presented during the DCCT/EDIC symposium suggested proteomics and genomics as possible surrogate markers, an idea Dr. Schmidt found

attractive not only because of the availability of

DCCT/EDIC samples, but also because research 

in these areas encourages basic researchers and

clinical trialists to partner with biotech companies,

thereby increasing the sample pool and fostering

further multidisciplinary action.

Following Dr. Schmidt's presentation, Dr. Bruce

Berkowitz, Professor, Department of Cell Biology 

and Opthalmology, Wayne State University School of

Medicine, Detroit, cautioned researchers to use the

most finely honed tools available, and as the MRI

community possesses an extremely powerful set of

tools for diabetic research, they ought to be enticed

to form partnerships.

Dr. Matthews commented that better data would

become available if researchers could get repeat

measures where some specific change or threshold

could be predefined. Surrogate markers for the

process as an endpoint would reduce regulators'

dependency on hard endpoints such as myocardial

infarction and death.

Dr. Josephine Briggs, Director, Division of Kidney,

Urologic, and Hematologic Diseases, NIDDK, offered

a follow-up to Dr. Matthew's remarks on working

with regulators, saying that she and Dr. Thomas

Hostetter, Director, National Kidney Disease

Education Program, NIDDK, have been in contact

with FDA regarding the development of a research

agenda that would lead to clarity in proteinuria as a

process marker.

How Can We Foster Identification of New

Therapeutic Targets and Agents?

Dr. Lloyd Paul Aiello, Assistant Director, Beetham

Eye Institute and Associate Professor of

Ophthalmology, Harvard Medical School, Joslin

Diabetes Center, suggested that increased consortium or network approaches would prove useful in

moving research findings into clinical trials more

rapidly. Excellent characterization and uniformly

standardized evaluation of consortia resources

would speed evaluation, provide larger sample numbers, and improve comparability between studies.

These repositories could also provide some fundamental analyses that are helpful or commonly utilized for this transition, either within the collected

samples or perhaps within the repositories. Benefits

would include improved comparability between

studies, more efficient and consistent evaluation,

and services for investigators who are in possession

of samples but are unfamiliar with a particular 

evaluation technique.

Dr. Aiello pointed out the need to rapidly identify,

evaluate, characterize, and implement new technologies that may become increasingly important both 

in the identification of new targets and the evaluation of potential surrogate markers. Such approaches, in addition to providing novel targets may provide cross-fertilization among different complication

disciplines and characterize new mechanisms by

which researchers could evaluate markers in clinical

trials in an efficient and rigorous manner.

During subsequent discussion, Dr. Aiello emphasized

that a functional genomics/proteomics approach,

conducted with homogenous patients or animal

models and identifying different targets, would aid

in fostering identification of new therapeutic targets.

Dr. Feldman proposed that some type 1 funds might

be directed toward discovery studies, which could

lead to new mechanisms, particularly in the proteomics field. Dr. Brownlee commented that discussion seemed to center on two general topics: (1) a

focus on optimizing what is currently available, and
DMICC ANNUAL REPORT 136 FY 2003

(2) the concept of discovery. Dr. Vlassara remarked

that the DCCT was basically an era of intervention,

focusing on the control and modification of blood

sugar; perhaps now it was time to add another

dimension to the DCCT.

How Can We Move Promising Therapeutic Agents

From Bench to Bedside?

Dr. Nigel Calcutt, Associate Professor, Department 

of Pathology, University of California San Diego,

used his experience with moving a molecule (prosaptide) from discovery to phase 2 clinical trials over 

a relatively short time as an analysis of the benchto-bedside procedure. According to Dr. Calcutt, doing 

so involves correctly targeted funding. He identified

several factors which contributed to the successful

process:

• Personal drive and focus of the Principal

Investigators, which included discovery of the

molecule and raising money through private funds

and venture capital.

• Availability of the STAR program, a fast-moving

funding mechanism, where funding was provided

in part by the State of California, part by the company of interest. A most important aspect of this

funding program is the recognition of the academic as Principal Investigator. The funding is therapy-oriented and results-driven, protects company

intellectual property, and provides for initial

proof-of-concept studies, allowing investigators to

produce the preliminary data necessary to qualify

for NIH funding.

• Availability of an NIH Request for Application

(RFA), an important aspect because it targeted

money at therapy-driven research, rather than

purely mechanistic-driven studies.

• Luck and opportunity for collaboration between

researchers.

Dr. Calcutt noted that, while these conditions are

admittedly unlikely to reoccur in the near future,

there are steps NIH can take to create a similarly

helpful environment. For example, NIH could fund

exploratory research programs that provide money

for 1-year rolling, results-driven projects, such as

those provided by the Juvenile Diabetes Research

Foundation (JDRF) International. An incentive for

academics to participate could be initiated through

the creation of modified STAR/SBIR (Small Business

Innovation Research) funding to include both 

industry and academia, where both parties would

receive recognition for participation. RFAs for R01s

to support therapy-driven research should be made

available, not to the exclusion of mechanistic-driven

research, but to allow for quicker progression.

Support systems, both informational banks and

funding sources, to connect Principal Investigators

having potential therapeutics with those skilled 

in phase 1 and 2 trials, might be made available

through the use of paired grants. Further, NIH could

provide assistance through both funding and information to small biotechnology companies to aid

them in moving potential therapeutic agents through

phase 1 and 2 trials.

During discussion, the point was made that using

surrogate markers and non-regulatory approved

endpoints may speed up the process. Dr. Calcutt 

suggested the formation of a body to negotiate a

compromise between NIH’s scientific position and

FDA's required position from a safety point of view.

Dr. Spiegel, Director, NIDDK, recommended Rapid

Access to Interventional Development (RAID), a 

program used at the National Cancer Institute that

provides, on a contract basis, some functions such

as producing a sufficient quantity or quality of a

product, by means that ordinarily would not be

available to an investigator who has a patented 

therapeutic agent. Production issues might also be

expanded through this program.

Dr. Fradkin pointed out the availability of the innovative partnerships RFA that pairs researchers

working in diabetes with scientists who have expertise relative to diabetes but who are working in other

fields, and proposed the notion that rather than a
DMICC ANNUAL REPORT 137 FY 2003

single grant, two paired grants might be a more

attractive option for investigators, a suggestion that

was met with general agreement.

Dr. Spiegel concluded with the observation that

future research teams ought to embody the concept

of a multidisciplinary approach, acknowledging that

equal credit for more than a single Principal

Investigator is a crucial aspect of team research.

What Are the Most Promising Opportunities To

Advance Research To Develop New Therapies for

Complications?

Dr. Brownlee posed several possible research questions for consideration by those in attendance:

• What are the mechanisms responsible for

microvascular complications?

• What are the mechanisms responsible for

macrovascular complications?

• What genetic issues determine the development

and progression of diabetic complications?

He expressed the opinion that further investigation

and definition of the issue of metabolic memory is

certainly necessary, including expansion of the 

concept to include other areas such as insulinresistance and fatty acid memory.

Dr. Brownlee recognized the importance of drugs

with regard to the prevention of diabetic complications, but remarked that perhaps a greater focus

ought to be placed on secondary prevention, since

the mechanisms responsible for initiation may not

be the same mechanisms responsible for progression of complications. Surrogate markers and a new

clinical study paradigm are also areas that he

believed warrant additional study, because current

paradigms are too costly and require too many years

to effectively screen treatments that show promise

in animal models.

It is generally accepted that, when considering

genetic susceptibility to complications, animal models such as those provided by the AMDCC provide

investigators with the advantage of using animals

with known genetic backgrounds. These models

ought to be further utilized.

As researchers focus design attempts on drugs

aimed at specific targets, Dr. Brownlee identified

high throughput screening for new therapeutic targets and agents as the new wave of the future.

Dr. Brownlee noted that the DCCT/EDIC symposium’s emphasis on multidisciplinary research and

collaboration between areas of expertise strongly

suggests that dual Principal Investigator grants and

exploratory research programs that promote discovery and innovative research should be a priority. In

conclusion, he listed the following areas as the most

important and most promising research opportunities:

• Development of a mechanism for real discovery

and innovation.

• Multidisciplinary efforts fostered through dual

investigator grants between researchers in complementary fields to produce innovative work.

• Funding for non-patented therapeutic agent trials.

Dr. Fradkin closed the session with the comment

that the meeting produced not only intriguing ideas

in the area of diabetes research, but identified available resources for carrying them to fruition.

DMICC ANNUAL REPORT 139 FY 2003

Speakers

Lloyd Paul Aiello, MD, PhD

Assistant Director, Beetham Eye Institute

Associate Professor of Opthalmology,

Harvard Medical School

Department of Eye Research and Opthalmology

Joslin Diabetes Center

One Joslin Place

Boston, MA 02215

Phone:(617) 732-2627

Fax: (617) 264-2710

aiellol@joslab.harvard.edu

Michael Brownlee, MD

Anita and Jack Saltz Professor of Diabetes Research

Department of Medicine

Albert Einstein College of Medicine

1300 Morris Park Avenue

Bronx, NY 10461

Phone:(718) 430-3636

Fax: (718) 430-8570

brownlee@aecom.yu.edu

Nigel Calcutt, PhD

Associate Professor

Department of Pathology

University of California San Diego

9500 Gilman Drive

La Jolla, CA 92093

Phone: (858) 534-5331

Fax: (858) 534-1886

ncalcutt@ucsd.edu

Saul Genuth, MD

Professor of Medicine

Division of Clinical and Molecular Endocrinology

Case Western Reserve University

Biomedical Research Building, Room 430

10900 Euclid Avenue

Cleveland, OH 44106

Phone:(216) 368-5032

Fax: (216) 368-1485

smg15@po.cwru.edu

Timothy S. Kern, PhD

Professor, Director, Center for Diabetes Research

Department of Medicine and Endocrinology

Case Western Reserve University

2109 Adelbert Road

Cleveland, OH 44106

Phone:(216) 368-6129

Fax: (216) 368-5824

tsk@po.cwru.edu

David M. Nathan, MD

Professor of Medicine

Harvard Medical School

Massachusetts General Hospital Diabetes Center

50 Staniford Street, Third Floor

Boston, MA 02114

Phone:(617) 726-2875

Fax: (617) 726-6781

dnathan@partners.org

Ann Marie Schmidt, MD

Associate Professor; Chief, Division 

of Surgical Science

Department of Surgery, P&S 17-501

Columbia University

630 West 168th Street

New York, NY 10032

Phone:(212) 305-6406

Fax: (212) 305-5337

ams11@columbia.edu
DMICC ANNUAL REPORT 141 FY 2003

DIABETES MELLITUS INTERAGENCY 

COORDINATING COMMITTEE MEETING: 

USE OF SPECIAL FUNDS FOR TYPE 1 

DIABETES RESEARCH

April 14, 2003

Building 31, Conference Room 6C

National Institutes of Health (NIH)

Bethesda, Maryland

SUMMARY MINUTES

Dr. Saul Malozowski, Executive Secretary of the

Diabetes Mellitus Interagency Coordinating

Committee (DMICC) and Senior Advisor for Clinical

Trials and Diabetes Translation, National Institute

of Diabetes and Digestive and Kidney Diseases

(NIDDK), opened the meeting, welcomed the

Committee members and their guests from the

Juvenile Diabetes Research Foundation

International (JDRF), and introduced Dr. Allen

Spiegel, Director, NIDDK.

Dr. Spiegel welcomed the attendees and explained

that DMICC is the venue for coordination of a 

number of diabetes functions. DMICC includes

members from the major NIH institutes and centers

(ICs), the Centers for Disease Control and Prevention

(CDC), and other U.S. Department of Health and

Human Services (DHHS) agencies. Dr. Spiegel

acknowledged the phenomenal support from

Congress for type 1 diabetes research. The 107th

Congress not only extended the initial special statutory funding program for type 1 diabetes research

from FY 2004 to FY 2008 but also increased the

funds to $150 million per year. This poses both an

opportunity and a challenge.

Dr. Spiegel announced that an evaluation report on

the original funding will be published in April or

May. The original January 2003 due date for this

report was changed by the latest bill to January

2007; however, NIDDK felt the report was of such

value and interest that it will issue it. In addition to

presenting the results accomplished from projects

supported from FY 1998–2002, the report includes

an Office of Management and Budget (OMB)

approved survey of all the investigators supported

through these funds. This survey, as well as an

analysis of the grants funded, documents that the

special statutory funds were instrumental in bringing new investigators into type 1 diabetes research

efforts as well as established investigators who had

not previously worked in this area. Dr. Spiegel

stressed that with this new stream of funding, it is

critical to examine carefully each of the commitments made for initiatives, consortia, and networks

that have been so productive and define milestones

and criteria for how they should be renewed. At the

same time, the best possible new initiatives need to

be identified to move forward. Dr. Spiegel then

turned the meeting over to Dr. Judith Fradkin,

Director of NIDDK’s Division of Diabetes,

Endocrinology, and Metabolic Diseases, who has

spearheaded the management of this special 

statutory funding program and crafted an ambitious

program to respond to this dual obligation for use

of the new funds.

Dr. Fradkin summarized the legislative history of the

type 1 special statutory funds, which have grown

from the original $30 million a year in 1998 to $150

million a year for FY 2004–2008, for a total of $1.14

billion for FY 1998–2008. This funding is intended

for use in trans-DHHS research efforts. Flexibility to

provide for a rapid response to emerging scientific
DMICC ANNUAL REPORT 142 FY 2003

opportunities will be preserved through use of pilot

and feasibility grants and short-term commitments

that could roll over to subsequent initiatives.

Research and voluntary communities are actively

involved in the planning and evaluation of the use 

of the funds. Most importantly the funds are not to

supplant research funded by regular NIH appropriations, but rather to augment and go beyond these

efforts to fund opportunities that would not ordinarily be addressed with regular funds. Based on these

principles, six major goals have been defined (see

box). To date the funds have established a largescale, collaborative, infrastructure of intensive initiatives that could not be pursued through R01s (i.e.,

investigator-initiated research); promoted innovative,

high-risk, high-impact research, particularly through

pilot feasibility grants; brought in new talent; and

fostered state-of-the-art technologies.

On May 16, 2002, an Advisory Panel of scientific 

and lay experts met and evaluated the research

efforts funded to date. The panel strongly endorsed

the six major goals noted above and the initiatives

resulting from them. They were also asked to identify new and highly promising opportunities for

research on type 1 diabetes. At the time the advisors

met, it was not known that Congress would be 

providing additional funding to support these

opportunities. Their recommendations will form 

the foundation for use of the newly appropriated

funds. These recommendations included:

• Continue support for investigator-initiated projects.

• Continue support of the consortia and the

resources that have been developed.

• Pursue development and application of new technologies.

• Encourage coordinated trans-DHHS and multidisciplinary approaches.

• Re-issue targeted Requests for Applications (RFAs)

to create ongoing research opportunities.

• Continue to attract new research talent to type 1

diabetes research.

In addition there were specific recommendations for

each of the six major goals that will be presented in

more detail. These recommendations from the May

meeting will be supplemented by focused meetings

on the major goals or subcomponents of the goals.

Dr. Fradkin elaborated on the May 2002 Advisory

Panel’s recommendations based on the six major

goals and sought the opinions and comments of

today’s participants.

Goals 1 and 2: Identify Genetic and

Environmental Causes and Prevent or Reverse

Type 1 Diabetes

To date, substantial resources have been used to

develop strong consortia. The Advisory Panel recommended promoting interactions, data sharing, and

coordination among these groups. They wanted to

see common bioinformatics platforms; ability to

integrate data; common consent forms, particularly

as samples are being put into repositories for use 

by future scientists; and standardized assays, for

instance for measuring HLA genotypes, antibodies,

and C-peptides as outcomes. The panel encouraged

support and interaction within the consortia for

ancillary studies such as the immune response studies from the Immune Tolerance Network (ITN) in

Six Major Goals
DMICC ANNUAL REPORT 143 FY 2003

conjunction with TrialNet clinical trials, as well as

partnerships with industry and academia. It was felt

that fast-track mechanisms were needed to facilitate

preclinical development and mechanisms for benchto-bedside support (e.g., production of biologics

when there is good preclinical data to suggest these

would be efficacious in a clinical trial, access to

GMP (good manufacturing practice) facilities to

make materials for use in humans, and support 

and access to animal tests for safety, toxicology,

immunoactivity, and efficacy).

Dr. Fradkin emphasized that close coordination is

essential, given the number of consortia and the fact

that they will be recruiting from the same population, as well as to promote the panel’s recommendations for common bioinformatics platforms,

standardization of assays, and partnerships. This

will mean coordinating recruitment and enrollment.

Particularly where multiple studies are recruiting in

a common geographic area, information exchange

and joint approaches to referring physicians will

maximize access to patients. Cross-identification of

families is needed to avoid duplication in submitting

specimens to repositories. Standardization of assays,

phenotyping, and consent forms will also be needed.

Dr. Fradkin said that NIDDK and the National

Institute of Allergy and Infectious Diseases (NIAID)

have already identified an individual who will be

asked take the lead in developing a coordination

mechanism. Other DHHS components responsible for

consortia will be asked to participate in this effort.

At Dr. Spiegel’s suggestion, the attendees described

the various consortia. TrialNet is a joint effort of

NIDDK, NIAID, the National Institute of Child Health

and Human Development (NICHD), and JDRF to test

methods to delay or prevent type 1 diabetes in

patients with new onset diabetes or at high risk for

diabetes. It also has a natural history component

allied with NIAID’s Immune Tolerance Network for

mechanistic assays to understand the ongoing

pathogenesis of type 1 diabetes. ITN is a joint effort

of NIAID, NIDDK, and JDRF. Its mission includes

conduct of clinical trials to test therapies and to

develop assays to monitor the induction, maintenance, and loss of tolerance. The areas covered are

kidney and islet transplantation, liver transplantation, and asthma, allergies, and autoimmune diseases among which type 1 diabetes is the major

focus of proposals to the ITN. To date, about 28 

percent of ITN funds have been directed to type 1

diabetes activities.

Dr. Fradkin said that ITN, TrialNet, and the Diabetes

Prevention Trial for Type 1 Diabetes (DPT-1), which

was the precursor of TrialNet, are good examples of

efforts, originally undertaken by the Institutes with

regular funds, where type 1 funds allowed expansion

of the research in ways that would not have been

permissible under regular funds.

The Autoimmunity Centers of Excellent (ACE), also

an NIAID initiative co-sponsored by NIDDK, is a

basic or preclinical research program, with clinical

components, in four centers that conduct trials with

the major focus on diabetes, although they work

with potentially more than 80 autoimmune diseases.

NICHD’s Trial to Reduce the Incidence of Type 1

Diabetes in the Genetically at Risk (TRIGR) is an

international clinical trial in which children at high

genetic risk for type 1 diabetes are randomized at

time of weaning to regular formula or Nutramigen®,

a partial hydrolysate of casein produced by Mead

Johnson. The outcome is the development of autoimmune antibodies to pancreatic antigens and eventually, if the children are followed long enough, onset

of type 1 diabetes. A preliminary trial about 5 years

ago with approximately 200 children indicated that

those who were put on Nutramigen® versus regular

formula had a slightly smaller incidence of diabetes,

although the data are not stable or statistically significant. The goal of the Triggers and Environmental

Determinants of Diabetes in the Young (TEDDY) 

initiative is to organize international efforts to identify infectious agents, dietary factors, or other environmental factors that trigger type 1 diabetes in

genetically susceptible individuals. The TRIGR and

TEDDY studies will have overlap in the sense that

they are both recruiting neonates at high genetic

risk at birth.
DMICC ANNUAL REPORT 144 FY 2003

The Centers for Disease Control and Prevention’s

SEARCH is an effort to look at childhood diabetes,

particularly type 1, but also type 2, to acquire more

accurate knowledge of the incidence and prevalence

of the diseases and to identify characteristics that

might clinically and epidemiologically distinguish

between traditional type 1 and so-called type 2 

diabetes in children. SEARCH will also follow these

children to examine quality of care. SEARCH’s six

centers are jointly funded by CDC and by type 1 special statutory funds.

CDC’s Genetics of Kidneys in Diabetes (GoKinD) is

an international effort to study the genetic risk 

factors for renal disease of type 1 diabetes and is

complementary to NIDDK’s Family Investigation of

Nephropathy and Diabetes (FIND). GoKinD is a joint

effort by CDC and, JDRF. FIND is a large consortia

of seven clinical centers and a genetics coordinating

center that is undertaking two studies on the susceptibility to diabetic nephropathy. About 85 percent

of the patients being recruited have type 2 diabetes

and about 15 percent have type 1. One strategy is to

look at concordant and discordant sibling pairs. The

other strategy, called mapping by admixture linkage

disequilibrium, is recruiting case controls to look at

genetic loci with regard to racial admixture. FIND

has been working closely with GoKinD in the 

informatics aspects, with the long-term goal of 

integrating the two databases so the identified susceptibility loci can be looked at in both databases.

The original goal was to look only at nephropathy

susceptibility, but with the support of the National

Eye Institute and some type 1 money, retinal photographs have been added and analysis will be done

of retinopathy susceptibility as well. NIDDK’s

Epidemiology of Diabetes Interventions and Complications (EDIC) study is also collecting genetic 

samples from subjects and their family members 

for analyzing susceptibility to complications in a

particularly well characterized clinical cohort. It

will complement FIND and GoKinD.

The International Type 1 Diabetes Genetic

Consortium (T1DGC), composed of three clinical 

networks and a data coordinating center, is studying

genes that influence the pathogenesis of type 1 

diabetes. It will generate a large standardized family collection of genetic and phenotypic data. The

NIAID’s International Histocompatibility Working

Group (IHWG) is a multi-institute sponsored activity

that includes the Office of the Director. IHWG is

looking at genetic components of a number of 

diseases, including the genetics of transplantation.

It includes more than 100 international programs

and has received some type 1 statutory funds for

SNP (single nucleotide polymorphism) identification

in 100 genes presumed to be possibly related to type

1 diabetes.

The Diabetes Research on Children Network

(DirecNet) is conducting studies of new glucose

monitoring devices to determine their accuracy and

utility in improving diabetes control and avoiding

hypoglycemia in children with type 1 diabetes. It is

led by NICHD with NIDDK participation.

Discussion

Dr. Fradkin asked everyone to be thinking about 

who from their consortia should represent them on

the consortia coordinating committee. There may be

multiple representatives so that subcommittees 

can be formed on specific issues, such as standardization of consent forms, phenotyping, assays, and 

so forth.

Dr. Fradkin explained that a Web site dedicated to

the type 1 special statutory funds program will

include information from each of the consortia on

their resources that will become available and when

they will be available. Type 1 funding will include a

requirement for public access by the general scientific community to these resources. The NIDDK is

creating a repository that will store and distribute

samples from clinical studies for use by the broader
DMICC ANNUAL REPORT 145 FY 2003

community. A requirement to deposit specimens 

into this repository is written into TrialNet and the

TEDDY grant awards. The Diabetes Control and

Complications Trial (DCCT) has developed a process

for access to samples from that study. DPT-1 will

soon have finished its second randomized trial 

and plans are being made to share available 

samples from their studies with the larger 

scientific community.

Dr. Daniel Rotrosen, Director, Division of Allergy,

Immunology, and Transplantation, NIAID, explained

that if ITN has sufficient material, samples will be

in the public domain along with data and protocols.

He pointed out that one problem, which also may 

be true of other trials, is the availability of sufficient

materials from young children due to mechanistic

studies already planned within the ITN protocols.

Material such as DNA that is readily available and

can be amplified is not a problem, but serum is

quite limited. This is also true of ACE. NIAID has not

yet established a mechanism for soliciting requests

for samples or distributing them. He suggested the

consortia would benefit from a central repository

with a standard mechanism to receive requests and

to distribute materials.

Dr. Gilman Grave, Chief, Endocrinology, Nutrition,

and Growth Branch, NICHD, said that since TRIGR

is looking at neonates, there are not many specimens available, although a predecessor study has

been collecting samples in Finland for 10 years.

They have also not addressed a distribution mechanism yet, but will probably ask other consortia

members for submission of specific information on

what they have in place for distribution.

Dr. Patricia Mueller, Chief, Diabetes and Molecular

Risk Assessment, CDC, explained that GoKinD was

designed to be a collection of samples that will be

in a CDC repository, so the collaborating investigators can do additional studies. Then they will be

made available to the broader research community,

probably through a modified Framingham model.

Proposals will be reviewed by a JDRF-appointed

committee of independent investigators.

SEARCH, according to Dr. Frank Vinicor, Director,

Division of Diabetes Translation, CDC, has established a repository and is willing to share data with

other investigators but does not have a mechanism

in place yet. Currently, CDC’s standard approach is

that investigators must submit a proposal that is

then reviewed by the SEARCH Executive Committee.

The SEARCH Executive Committee will be looking at

the challenge of how to strike a balance between

making the samples publicly available for studies

that have an appropriate scientific base without

using them up.

Dr. Fradkin said that peer review can be very useful

in that regard. EDIC has two peer-reviewed program

project (P01) grants that will use EDIC samples and

are funded with separate NIH funds. One is an

NHLBI-supported P01 at the University of South

Carolina and the other is an NIDDK-supported P01

at the University of Washington.

Dr. Fradkin recommended that in making samples

available to the broader community, it is better if

those who collect the samples are not the sole 

determinants of who may use them. If the collection

of the samples has been supported by substantial

type 1 diabetes special statutory funding resources,

there is a real obligation to share them, not just by

making them available among the collaborating

investigators, but by placing them in the public

domain. What is needed is an in-place mechanism to

provide support to those who will do ancillary studies with the samples, independent of the control of

the investigators. She urged everyone to be aware of

the importance of this. In EDIC, for example, some

of the review committee members are from EDIC,

but it is not an EDIC committee. This provides

insights into the use of the samples that derive from

the knowledge of EDIC investigators who know the

study design in detail, but does not give the study

group exclusive use of the samples. Ideally, the

terms and conditions of the notice of grant award 

or the RFA should include this understanding to

prevent any difficulty in acquiring access to the

samples or data. Under contracts or U01s (cooperative agreements), there is more ability to influence
DMICC ANNUAL REPORT 146 FY 2003

the process than under an R01. Dr. Fradkin

explained that agreeing to share the samples and

associated de-identified information will be a factor

in deciding support for type 1 activities.

Dr. Vinicor brought up the related issue of the HIPPA

(Health Insurance Portability and Accountability Act

of 1996) rules and regulations regarding patient 

privacy of personal health information that will also

affect the sharing of samples and data. The administrative and legal processes affected by the HIPPA

rules do not have to be a major barrier but it is

important to be aware of them as a potential 

impediment. Dr. Fradkin agreed that the consortia

coordinating group needs to look at HIPPA, particularly with regard to consent forms. While these

investigations are ongoing and there is regular 

contact with the subjects is the best time to get

proper consents for sharing of data and samples.

Dr. Peter Savage, Director, Division of Epidemiology

and Clinical Applications, National Heart, Lung, and

Blood Institute (NHLBI) remarked that NHLBI,

through its considerable recent experience in sharing data and samples, has noticed people interpret

fairly clear statements in a wide variety of ways. He

urged the group to have a standardized procedure

for securing data or samples and one that certainly

includes the legal implications of the HIPPA regulations. He also stressed the importance of the agreement’s not being so broad that later, because of

commercial interest or some other consideration,

there is a lot of opposition to it. Dr. Fradkin added

that it would also be important to proactively talk

with people about the language in the Notice of

Grant Award, since there is a tendency among investigators not to read the detailed award provisions.

The meaning of the terms and conditions should be

discussed and clarified to ensure they are agreed to

and clearly understood. Dr. Mueller also expressed

support for a consistent mechanism for making the

samples available. The consensus was that this

would be advantageous to everyone.

Dr. Robert Goldstein, Chief Scientific Officer, JDRF,

agreed with the type 1 Advisory Panel’s recommendation that coordination among the consortia (and

he included the DCCT/EDIC) was extremely important and offered untold opportunities for the future,

especially regarding the data centers and sample

repositories. He said the international community

would welcome a standard procedure for sharing

these resources across borders. In all JDRF grant

awards where sample collection takes place and has

value, JDRF has made ultimate sharing mandatory

and the notion of a public resource preeminent,

despite variations in international rules and guidelines. The lack of a standard consent form and standardization of sample collecting and measurement

across international borders is a barrier to providing resources from these studies to U.S. researchers.

Dr. Goldstein added that once rules and guidelines

are established, the clinical trials funded by JDRF

could contribute to a centralized effort other populations and materials that do not duplicate those

from NIH. Dr. Fradkin remarked that many of the

type 1 diabetes consortia are international in scope.

Making funding contingent on willingness to supply

the samples has been an issue with the type 1

genetic consortia because of the lack of standardization of consent processes internationally.

Dr. Goldstein also urged that industry be granted

access at some point in time to some of the

resources from this phenotypically valuable patient

population, which is too small in number compared

to those populations with other diseases to be

assessed in this way by industry. However, if industry is presented with a well-documented population,

regardless of size, it is then commercially attractive

for them to study that group.

Dr. Goldstein commented that it would be extremely

helpful to his organization, and surely to others,

including Congress, to have a summary of the

amount of money the NIH ICs spend on type 1

research as a whole, since this will not be included

in the type 1 special statutory funds’ evaluation
DMICC ANNUAL REPORT 147 FY 2003

report. Dr. Spiegel replied that to do what Dr.

Goldstein requested would require a special mechanism to collect the information across all ICs, which

is being done for the special statutory funding program for type 1 diabetes research. He explained that

Dr. Elias A. Zerhouni, NIH Director, in his addresses

to Congress presents overarching themes for all the

diseases within the ICs areas of responsibility,

rather than specific diseases. However, NIDDK and

the other institutes publish many documents each

year covering their advances and opportunities in

intramural and extramural research.

Dr. Rotrosen said that due to the strong interactions

he has had with NIDDK over the years, he is confident that NIAID and NIDDK have good mechanisms

for addressing overlap. He suggested that CDC, the

other ICs, and multiple partners meet more frequently to ensure the same level of communication.

Dr. Fradkin assured him that CDC’s funded research,

for instance, is very discrete from what is happening at NIH. GoKinD and FIND are complementary,

but recruiting different populations. SEARCH is not

duplicated by any NIH projects she is aware of. She

agreed that meetings facilitated communication and

added that a coordination mechanism for the consortia will also provide DHHS staff with a forum to

obtain progress reports and hear about events in

which they are not directly involved.

Goal 3: Develop Cell Replacement Therapy

Dr. Fradkin noted that the May 2002 Advisory Panel

was very enthusiastic about the Beta Cell Biology

Consortium (BCBC). The panel strongly recommended expanding the BCBC, involving new researchers,

and integrating the research with other consortia’s

efforts to identify markers for imaging beta cells

and for assessing the quality of islets for transplantation. This is ongoing.

In transplantation, there are several coordinated

efforts, including the ITN, that are looking at

immunomodulation and tolerance. There is also a

primate consortia that is looking at a number of

transplantation-related issues. The Advisory Panel

felt that in addition to these, there were other areas

that needed to be developed. These included:

• Improving harvesting, isolation, assessment, and

preservation.

• Improving engraftment (insights from angiogenesis) and function.

• Conducting clinical trials other than for tolerance

(i.e., site and method of transplant, less toxic

immunosuppression).

• Looking at xenotransplantation (islets, reagents).

• Expanding animal and pre-clinical research.

NIDDK is planning an advisory meeting on May 30,

2003, with the National Center for Research

Resources (NCRR), NIAID, and JDRF to discuss

transplantation initiatives such as expanding the

primate consortia. The date for the meeting was

selected to coincide with a meeting in the metropolitan Washington, D.C. area, of the American Society

of Transplantation.

Discussion

The discussion on transplantation included the 

following points:

• Multiple groups are discussing the issues, including a trans-NIH coordinating committee and an

Executive Committee from Secretary Tommy

Thompson’s office at DHHS. Close coordination

among these groups is needed.

• The trans-NIH committee has largely focused on

major organ transplantation but will include

islets, but not the full pancreas, in its FY 2004 initiatives. It will be FY 2005 or beyond before they

address xenotransplantation.
DMICC ANNUAL REPORT 148 FY 2003

• The Secretary’s office is aware of some high profile

advances in transplantation, including islet transplantation, and of third-party payer issues for 

kidney transplantation.

• Key issues in islet transplantation are new

approaches to genomic assessment of the 

quality of the islets; possibly the use of xeno

islets or islets derived from stem cells; and 

development of better tolerance or immunosuppressive approaches.

• The Secretary’s office also has an advisory committee on xenotransplantation, largely taking a

very broad view and focusing on scientific feasibility and industry interaction with the Food and

Drug Administration.

• Although xenotransplantation research goes back

about 20 years, it has not had the success anticipated. Now that transgenic pigs engineered to prevent hyperacute rejection are available, funding

may attract new investigators and encourage

research in this area as an alternative approach 

to treat type 1 diabetes.

• Encapsulation is an area that also has not had

significant success so far, but if it is de-coupled

from xenotransplantation, small businesses might

be interested in the two fields separately. Currently, there is confusion about their relationship.

• NIDDK provided additional funding through its

diabetes centers in 2002 to promote research in

encapsulation and attract new talent in this area

of research.

• To propel the technology forward, Small Business

Innovation Research (SBIR) programs were recommended as a possible approach, subject to peer

review, to getting small businesses, possibly in the

bioengineering community, interested in encapsulation and in xenotransplantation as separate

endeavors. In addition non-SBIR funds still may

be needed to involve the right people in investigating the xenotransplantation and encapsulation

issues.

• Prior to FY 2001, there was no set-aside for small

business from the type 1 special statutory funds.

Currently the NIDDK funds the small business

commitments generated by the special statutory

type 1 diabetes funding from its appropriated

funds. Beginning in 2004 special statutory type 1

funds will be used for this set-aside.

Goal 4: Prevent or Reduce Hypoglycemia in Type

1 Diabetes

Dr. Fradkin noted that hypoglycemia is a major

problem for those living with type 1 diabetes.

The May 2002 Advisory Panel identified several 

new opportunities for research, particularly to 

bring in some of the latest technologies from neuroscience and neuro-imaging to prevent or reduce

hypoglycemia. Their recommendations included 

the following:

• Study the mechanism of restoration of hypoglycemia unawareness and counter-regulation in

new transplant recipients.

• Recruit neuroscientists and brain-imaging specialists to study glucose-sensing mechanisms in

the brain, islets, and other glucose-sensing tissues

(e.g., muscle, liver).

• Understand the brain effects of recurrent hypoglycemia (especially in young children) using brain

imaging technology (PET) and assessment of 

glucose metabolism.

• Foster application of discovery of sensors for

brain substrates and neurotransmitters to type 

1 diabetes.

• Identify transporters that may be involved in

hypoglycemia.
DMICC ANNUAL REPORT 149 FY 2003

• Understand how sleep promotes hypoglycemia.

Dr. Fradkin complimented Dr. Grave for how quickly

DirecNet became established. It has already initiated and completed studies on the GlucoWatch and

the Minimed Medtronic continuous sensor. Dr. Grave

credited the data coordinating center and DirecNet’s

five clinical centers. Investigators at the centers

have already issued about eight abstracts and 

some papers.

Goal 5: Prevent or Reduce Complications in Type

1 Diabetes

An overall recommendation from the May 2002

Advisory Panel that Dr. Fradkin noted was the need

to bring together those working on different complications in order to share information and ensure

maximum use of the information acquired, for

instance from existing animal models. While the

Animal Models of Diabetic Complications Consortium (AMDCC) has been helpful in doing this, there

are potential expansions of this effort to advance

the understanding of complications. The Advisory

Panel recommended facilitating animal research

that addresses multiple complications and evaluates

multiple tissues. They also suggested developing

resources for distributing animals with prolonged

hyperglycemia and developing a mechanism for preclinical pharmaceutical testing of animal models.

Development of animal models provides a means of

testing concepts from basic research to identify the

best places to invest funds for clinical research.

In addition to those from the May 2002 Advisory

Panel, Dr. Fradkin brought recommendations from

the April 10–11, 2003,

DCCT/EDIC 20th anniversary

meeting. The participants at

this meeting had focused on the

concept of a possible “metabolic

memory” resulting from early

intensive glycemic control. In

the tight control group, the

onset of complications tended

to be delayed long after the

tight control was ended, even

though the subjects’ glycemic

levels became approxi-mately

the same as those of subjects in

the standard treatment group.

Following the main meeting, the

group met with DMICC to contri-bute suggestions for further research on complications in type 1 diabetes (see box). Animal models

were a major subject of discussion. It was suggested

that the animal model consortium be a venue for

bringing researchers of different disciplines together through regular confer-ences and symposia. It

was con-sidered important to bring the trans-NIH

and trans-DHHS groups together with the consortium to ensure that all of the complications are

being considered and to develop strategies to coordinate, expand, and broaden the joint efforts.

Currently NIDDK provides coordination for the consortium, and NHLBI administers a number of the

awards.
DMICC ANNUAL REPORT 150 FY 2003

Dr. Fradkin briefly spoke of the other recommendations, including expanding the cores as a resource

so that those with expertise in one organ could send

their animals to be characterized in terms of other

organs. Standardized characterization would help to

not only find genes but to identify animals that have

a higher innate susceptibility, which is important in

deciding which animals to use to create knockouts

that are potentially susceptible to complications.

Other key areas are to learn which cell types are

involved in the development of complications and to

take advantage of the progress in integrating the

potential mechanisms of complications by expanding multidisciplinary approaches that involve

inflammatory expertise and so forth. Clinical trials

still need reliable biomarkers to make them more

efficient. Finally, the goal of moving from bench to

bedside requires exploratory results-driven projects

and assays to determine which agents should be

carried forward to clinical trials so funds are not

spent pursuing ultimately unfruitful things.

Discussion

Dr. Josephine Briggs, Director, Division of Kidney,

Urologic, and Hematologic Diseases, NIDDK, spoke

of the value of NIDDK’s partnership with NHLBI.

The current animal model consortium includes three

projects on large animal models and a group of

investigators who are coordinating efforts on the

mouse. The mouse group is focusing on genetically

engineering target genes to identify cell types 

specific for complications and on other genetic

strategies to make the mouse more susceptible. The

consortium has made substantial progress in developing agreement on assessment protocols for the

mouse and overcoming the sizable technical problems in doing this assessment in the mouse. The

nephropathic and neuropathic groups within the

consortium are reasonably well advanced; there was

no retinopathy proposal originally, but a group of

investigators who will be looking at retinopathy is

being brought in. This is an area where the consortium would like to see substantially more effort.

Dr. Briggs explained that some things in the broad

area of animal models are not being addressed yet.

The group has not undertaken extensive investment

in the genetics susceptibility of loci to be able to

translate them into the mouse to see if they have

impact. It also does not include any rat studies.

People in the field report that since the rat is being

used and the protocols for identifying diabetic 

complications vary wildly from laboratory to laboratory, more standardization of protocols is needed.

What needs to be understood is that the genetic

manipulation to develop animal models is not an

enormously rapid process. It takes about a year to

make a knockout, and this group is just reaching the

point where they have models that it makes sense 

to talk about distributing. The consortium meets

every 2 to 3 months, but these have not been meetings open to others. Dr. Briggs heard a strong 

message at the April 11 meeting that to open these

meetings and expand their dialog would be valuable

both to those within the consortium and to the

broader community.

Dr. Goldstein agreed that it would be valuable to use

such a venue to bring together in one place people

concerned about eye disease and nerve disease and

kidney disease. To date, there has been no common

forum or place to have such discussions. If this can

be done around animal model discussions, it would

help everybody. Dr. Spiegel added that it is important to involve the National Eye Institute (NEI) and

the National Institute of Neurological Disorders and

Stroke (NINDS).

Dr. Savage said that a NHLBI working group is going

to be exploring opportunities to better understand

the causes of macrovascular disease in type 1 diabetes. Dr. Paul Nichols, Program Director, Systems

and Cognitive Neuroscience Program, NINDS, added

that there is an interest in his group to study 

various aspects related to diabetes such as pain

mechanisms, stroke, cognitive deficits in type 1 diabetes, and sleep research, particularly its relationship to hypoglycemia. They are interested in doing a

diabetes initiative or preclinical trial involving neurological complications, which they feel would not

require a great deal of money.
DMICC ANNUAL REPORT 151 FY 2003

Dr. Goldstein commented on the compelling discussion at the April 11 DMICC meeting about providing

funds for a program to encourage high-risk, innovative studies of novel therapeutics for complications

and immunomodulation. Such a program would

require a different review process. It might also

attract researchers who are not currently involved

in diabetes, but who have expertise to contribute.

Dr. Fradkin replied that the bench-to-bedside RFA,

supported across multiple institutes, addressed that

type of focused preliminary studies. The RFA, which

encourages collaboration between basic research

scientists and clinical scientists, has been successful and probably will be issued annually as an

impetus and path for innovative studies. However,

additional mechanisms are needed to move new

agents forward into trials. A mechanism similar to

that of the National Cancer Institute’s (NCI’s) Rapid

Access to Intervention Development (RAID) is also

being considered. (RAID is a mechanism to provide

investi-gators with access to drug development

resources in order to bring therapeutic applications

that originate in an academic laboratory through

preclinical development.)

Dr. Fradkin agreed with Dr. Goldstein that a special

peer review process for applications for use of the

RAID mechanism will be essential, both to foster a

rapid response and because such efforts tend to be

very expensive. It is important to invest the type 1

funds in development of the most promising agents.

In addition to proposals for new therapeutics for

complications, there are some proposals coming out

of ITN and TrialNet that need preclinical development, mouse studies, toxicological studies, and such

that the individual consortia members are not

equipped to do; the consortia could benefit from

such a mechanism. In addition, availability of an

impartial review for access to this type of preclinical development mechanism might challenge the

broader community to develop new therapeutics.

Goal 6: Attract New Talent to Research in Type 1

Diabetes

In introducing Goal 6, Dr. Fradkin said that the

Advisory Panel clearly recommended major bold

new initiatives with these funds. Complications may

be a good area to pilot these since relatively fewer

resources have been directed to them in the previous

funding years and, even though there are excellent

investigators in the area, it is a fairly small field and

one that needs new talent. This might be a place for

a mechanism to attract those who would not be typically attracted by an R01 award. The Panel recommended encouraging multidisciplinary teams and

novel technologies, supporting high-impact goals,

and, most importantly, making continued funding

contingent on milestones.

A DARPA (Defense Advanced Research Projects

Administration)-like review was also recommended.

Such a review was discussed at a recent JDRF scientific advisory board meeting. It assesses a

researcher’s capabilities, track record, and the novelty of the proposal being offered, rather than focusing on the technical aspects that are central to an

R01 review. For example, it does not require the

level of preliminary data required for an R01. The

idea is for the review to be flexible and examine

where opportunities lie in the applications. Because

acceptance is based primarily on potential, it is

essential to have specific milestones and ongoing

evaluations. DARPA projects are intended to develop

a specified application driven by a pre-defined outcome. They usually have a lifetime of 3-5 years and a

large budget of $5-10 million.)

Challenging topics might include new animal models focused on complications, surrogate markers,

angiogenesis, and endothelial biology. The challenge

will be to take on a difficult problem such as developing surrogate markers or a high throughput assay

that could be used to move things from the bench to

the bedside. Hopefully this will bring in people,

such as endothelial developmental biologists, cell

biologists, or those with expertise in angiogenesis,

who are not currently focused on diabetes and its
DMICC ANNUAL REPORT 152 FY 2003

complications. This has worked well for cancer

research. If this is successful in attracting the right

people to the field, then it could be expanded in subsequent years to other goals.

Discussion

Dr. Rotrosen cautioned that the challenge opportunities be well-defined, since most investigators believe

their project is innovative and challenging. Also, a

useful technique that NIAID had for their challenge

grant initiatives was to not require matching funds

from industry and to provide multiyear funding in

one year, which is atypical, but got the attention of

companies and academic investigators who otherwise might not have been interested.

Dr. Spiegel was impressed at the April 10–11, 2003,

DCCT/EDIC meeting by the amount of important talent that has largely focused on the cancer area, but

not on diabetes. Angiogenesis, for instance, has burgeoned dramatically in the cancer field. He said it

will be important to find an inducement for these

researchers to shift their focus and apply their abilities in the diabetes field. He urged the group to

seize the opportunity this year to tap into the

tremendous talent pool that is available—to attract

those who have successfully solved problems in one

area and have them focus now on diabetes—both

with regular appropriations and the special statutory type 1 funds. Integrating industry also is an issue

for which an appropriate program is needed.

Dr. Fradkin asked if there was interest in a pilot

program to identify one or two areas of focus

regarding fundamental biology related to complications. Understanding the biology might then provide

the opportunity to develop biomarkers, surrogate

outcomes, and other measures to move novel therapeutics forward. Before looking for therapies, it is

necessary to have a reliable assay that will accurately measure the outcome of the intervention

process; this is not presently available for complications. That could be the focus of the challenge.

Dr. Charles Queenan, Chair of Research, JDRF, suggested that, rather than an all-or-nothing approach,

portions of innovative proposals could be approved

or applications could be combined, particularly with

a DARPA-like review mechanism.

Dr. Savage thought that seed funding might be the

best approach to take at the present time rather

than soliciting large multidisciplinary projects since

many areas related to diabetes complications are

still relatively primitive. For instance, there are

some very specific things to be defined in the area of

biomarkers, which are needed for clinical trials.

Another area of interest would be to try to identify

those who are at risk, and those who appear to be

protected, by studying people who have diabetes for

20 or 30 years and do not develop complications versus others who develop them very early.

Seeding Collaborative Research Supplements for

Shared Resources

Dr. Fradkin proposed providing supplements to regular NIH grants in a new mechanism to seed multidisciplinary collaborative research. The supplements

would enable a person in one area to seek out others

whose expertise, along with core or shared

resources, would benefit collaborative research

funded through a peer-reviewed mechanism. There

would be very clear definitions on how the supplements could be used. They could not be used for

merely continuing the investigator’s ongoing

research projects. The seed money would be expected to “jump start” important collaborative research

efforts, bring in new talent, and lead to other beneficial consortia. Potentially, it would foster the following types of initiatives:

• Establishment of research consortia among

researchers in complementary fields to investigate:

• Multiple issues affected by vascular disease.
DMICC ANNUAL REPORT 153 FY 2003

• Inflammation, immunology, and endothelial 

biology.

• Sharing of unique reagents, technology, or 

complementary expertise.

• Funding two to five researchers, each with independent peer-reviewed support.

• Supporting a collaborative project within the

scope of individual grants.

Projects would be peer-reviewed by senior NIH staff,

both initially and through ongoing evaluations. The

projects would be assessed on their novelty or

uniqueness, the added value they will bring to

underlying research, and their potential benefit to

type 1 diabetes research.

Report on Consortia and Resources

The current consortia will be reporting in May 2003

on the special statutory type 1 funds they have been

awarded to date. Their reports will include the following topics:

• Goals and structure (i.e., steering committee, sites,

Web sites).

• Accomplishments to date.

• Milestones for future accomplishments.

• Evaluations (e.g., by External Advisory Committee,

reports, recommendations).

•Coordination efforts with other consortia.

• Materials, products, and samples that will be

made available to the scientific community.

• Future support requested.

With the exception of the budgets, the reports will

be posted on the type 1 diabetes special statutory

funds Web site that is in the process of being created. The Web site will describe the consortia and the

resources available through the consortia. It will

provide a central resource for people seeking information on type 1 diabetes research, including links

to non-special statutory funded research as well as

links to the individual consortia Web sites.

Opportunities for funding will also be listed.

Dr. Fradkin said that the recommendations by 

the May 2002 Advisory Panel have been carefully

reviewed and mechanisms are being put into place

to fund these in the FY 2004 budget.

New or Re-Issued Solicitations

Goals that the Advisory Panel members were enthusiastic about will be supported by re-issued and

new solicitations, including the following:

• Innovative Grants Immune Tolerance

• Bench-to-Bedside Research

• Innovative Partnerships for Type 1 Diabetes

• Ancillary Studies to Type 1 Diabetes Consortia

• Expand Beta Cell Biology Consortium

• Expand Non-Human Primate Consortium

• Hypoglycemia.

It is also likely that additional solicitations may be

issued based on recommendations from upcoming

meetings on the role of inflammation in CVD complications, beta cell imaging, and proteomics and 

islet transplantation.

Dr. Fradkin explained that these will be similar to

previously issued solicitations in these areas of

opportunity but will be amended based on the May

2002 Advisory Panel and other advisory committee

and scientific meetings. The innovative partnerships

RFA serves as a “talent scout” by fostering collaboration between researchers with expertise in type 1
DMICC ANNUAL REPORT 154 FY 2003

diabetes and researchers whose expertise, while 

not in type 1 diabetes, is relevant to it. A draft of 

the innovative partnerships RFA has been circulated

to the ICs, and NIDDK has received suggestions

from individual ICs on topics that are within the

mission of the IC. This is not what the Institute is

looking for with this RFA. It is intended to focus 

on opportunities identified by the external Advisory

Panel, including cross-cutting topics that would

involve multiple ICs, particularly with regard to

complications and studies looking at various tissues

and organs. The RFA will be re-circulated based 

on the recommendation from the April 11, 2003,

meeting to create a mechanism for paired grants 

in order to attract new talent. All ICs were invited 

to contact Dr. James Hyde, NIDDK, if they wished 

to participate.

SBIR and STTR Potential Program Announcement

Topics

NIDDK is required to set-aside a portion of the type

1 special statutory funds for small business. For FY

2004, the following areas will be available for development through SBIR or Small Business Technology

Transfer (STTR) programs:

• Drugs or protocols to induce tolerance or reduce

autoimmunity.

• Methods to assess progression and immune modulation in type 1 diabetes such as:

• Imaging/tracking of autoimmune cells

• Proteomic approaches

• Genetic, proteomic, or other improved tests for

identifying individuals at risk.

• Islet transplantation:

• Enhance islet survival, engraftment, in vivo

regeneration

• Improve islet isolation methodologies:

media, collagenase

• Islet encapsulation

• Development of a closed-loop artificial 

pancreas.

• Application of new technology to complications

research, such as:

• Chips for assessment of tissues and organs

involved in complications

• Biomarkers

• Improved animal models of type 1 diabetes and

complications for testing new therapies such as

embryonic stem cells from a NOD (non-obese 

diabetic) mouse.

NIDDK will be putting together an SBIR solicitation

that will be a multi-IC solicitation. Dr. Fradkin invited those present to send her other suggestions for

discrete areas where small businesses could make 

a contribution and to indicate their interest in participating in this solicitation.

Asked if companies working with human embryonic

stem cells would be eligible, Dr. Spiegel answered

that the funds could only be used to support those

with cell lines already on the registry, which is the

same restriction that applies to academic investigators. For SBIRs/STTRs, the companies must be U.S.

owned and there is a limitation on the number of

employees and on gross revenues. Dr. Goldstein

added that the ones with approved cell lines are

already being heavily solicited by NIH. The majority

are not eligible for SBIR funds. Dr. Goldstein urged

that new therapies be sought for the complications

of type 1 diabetes.

Schedule of Advisory Meetings To Inform the

Planning Process

Dr. Fradkin concluded her presentation with a slide

listing the advisory meetings that would be contributing to the type 1 special statutory funds planning process. These include:
DMICC ANNUAL REPORT 155 FY 2003

• DMICC Meeting on Complications of Type 1

Diabetes, April 11, appended to the DCCT/EDIC

20th Anniversary Meeting, April 10–11, 2003

• Inflammation and Cardiovascular Disease,

April 27–28 (with NHLBI and JDRF)

• Beta Cell Imaging, April 21–22

• Proteomics and Diabetes, April 24–25

• Transplantation, May 30 (with NIAID, NCRR,

and JDRF)

• Integration of Clinical Consortia, June 2003

• External Advisory Committee (EAC) Meetings 

of Ongoing Consortia

• Beta Cell Biology Consortium, May 4–6

• International Type 1 Diabetes Genetics

Consortium, July 15

• TEDDY, October 2003

Dr. Fradkin welcomed all those present to attend

these meetings and urged those who are leading

other consortia to notify the other members of the

EAC meetings coming up for their groups and where

they are being held. Dr. Goldstein announced that an

NIH stem cell meeting is being held June 12, that

some might be interested in. Dr. Spiegel added that

there would be a symposium in the morning and

workshops in the afternoon. There are a number of

related activities taking place that week. The NIH

event will be preceded by a meeting of the new Stem

Cell Society that will be held in Washington, D.C.,

and it will be followed on June 13 by a joint

NCRR–NIDDK meeting of the infrastructure board.

Dr. Fradkin thanked those present for their participation. She emphasized that she is looking forward

to working in partnership with them in these exciting times to carry out the responsibilities and challenges to use the type 1 special statutory funds in

promising ways and to do so wisely.

The meeting was adjourned at 11:05 a.m.
DMICC ANNUAL REPORT 157 FY 2003

Participants

Ricardo A. Brown, PhD

Program Director, Biomedical Research Branch

Division of Basic Research

National Institute on Alcohol Abuse 

and Alcoholism

National Institutes of Health

Willco Building, Room 402

6000 Executive Boulevard, MSC 7003

Bethesda, MD 20892

Phone: (301) 443-2239

Fax: (301) 594-0673

ricbrown@mail.nih.gov

Patricia Bryant, Ph.D

Director, Behavior and Social Science Research

Division of Population and Health 

Promotion Sciences

National Institute of Dental and 

Craniofacial Research

National Institutes of Health

Building 45, Room 4AS-43A

Bethesda, MD 20892

Phone: (301) 594-2095

Fax: (301) 480-8322

bryantp@de45.nidr.nih.gov

Michelle Cissell

Juvenile Diabetes Research Foundation

International

120 Wall Street

New York, NY 10005 

Phone: 1-800-533-CURE (2873)

Fax: (212) 785-9595

Peter Dudley, PhD

Program Director, Retinal Diseases Program

National Eye Institute

National Institutes of Health

6120 Executive Boulevard, Suite 350

Suite 350, MSC 7164

Rockville, MD 20852

Phone: (301) 451-2020

Fax: (301) 402-0528

pad@nei.nih.gov

Thomas Eggerman, MD, PhD

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

6707 Democracy Boulevard

Two Democracy Plaza, Room 697

Bethesda, MD 20817

Phone: (301) 594-8813

Fax: (301) 480-3503

eggermant@extra.niddk.nih.gov

Jody Evans

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

6707 Democracy Boulevard

Two Democracy Plaza, Room 697

Bethesda, MD 20817

Phone: (301) 594-8843

Fax: (301) 480-4125

EvansJ@extra.niddk.nih.gov

Carol Feld

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

31 Center Drive

Building 31, Room 9A07

Bethesda, MD 20852

Phone: (301) 496-6623

Fax: (301) 496-7422

feldc@hq.niddk.nih.gov
DMICC ANNUAL REPORT 158 FY 2003

Judith Fradkin, MD – Speaker 

Director

Division of Diabetes, Endocrinology 

and Metabolic Diseases

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

2 Democracy Plaza

6707 Democracy Boulevard, Room 689

Bethesda, MD 20892

Phone: (301) 594-8814

Fax: (301) 480-3503

fradkinj@ep.niddk.nih.gov 

Robert Goldstein

Juvenile Diabetes Research 

Foundation International

120 Wall Street

New York, NY 10005

Phone: 1-800-533-CURE (2873)

Fax: (212) 785-9595

Gilman D. Grave, MD

Chief, Endocrinology, Nutrition,

and Growth Branch

Center for Research for Mothers and Children

National Institute of Child Health 

and Human Development

National Institutes of Health

6100 Executive Boulevard, Suite 4B-11

6100 Executive Boulevard, MSC 7510

Bethesda, MD 20892

Phone: (301) 496-5593

Fax: (301) 480-9791

gg37v@nih.gov

Mary Hanlon, MD

National Institute of Diabetes and Digestive and

Kidney Diseases

National Institutes of Health

31 Center Drive

Building 31, Room 9A05

Bethesda, MD 20852

Phone: (301) 496-6623

Fax: (301) 480-6741

mh448u@nih.gov

Anthony Hayward

National Center for Research Resources

National Institutes of Health

6701 Democracy Boulevard

One Democracy Plaza, Room 906

Bethesda, MD 20817

Phone: (301) 435-0791

Fax: (301) 480-3661

haywarda@ncrr.nih.gov

James Hyde, MD

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

2 Democracy Plaza

6707 Democracy Boulevard, Room 680

Bethesda, MD 20892

Phone: (301) 594-7692

Fax: (301) 480-3503

HydeJ@extra.niddk.nih.gov

Richard Knazek, MD

Medical Officer

National Center for Research Resources

National Institutes of Health

6705 Rockledge Drive

Rockledge One, Room 6128

Bethesda, MD 20892

Phone: (301) 435-0790

Fax: (301) 480-3661

richardk@ncrr.nih.gov

Maren R. Laughlin, PhD

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

2 Democracy Plaza

6707 Democracy Boulevard, Room 6101

Bethesda, MD 20892

Phone: (301) 594-8802

Fax: (301) 480-3503

laughlinm@extra.niddk.nih.gov
DMICC ANNUAL REPORT 159 FY 2003

Saul Malozowski, MD, PhD, MBA

Senior Advisor for Clinical Trials 

and Diabetes Translation

Division of Diabetes, Endocrinology,

and Metabolic Diseases

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

6707 Democracy Boulevard,

Room 679, MSC 5460

Bethesda, MD 20892

Phone: (301) 451-4683

Fax: (301) 480-3503

sm87j@nih.gov 

Dennis F. Mangan

National Institute of Dental 

and Craniofacial Research

National Institutes of Health

45 Center Drive

Building 45, Room 4AN12J

Bethesda, MD 20852

Phone: (301) 594-2421

Fax: (301) 480-8318

dm38q@nih.gov

Ronald Margolis, PhD

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

6707 Democracy Boulevard, Room 6107

Bethesda, MD 20892

Phone: (301) 594-8819

Fax: (301) 435-6047

MargolisR@extra.niddk.nih.gov

Paul L. Nichols, PhD

Program Director, Systems and 

Cognitive Neuroscience Program

National Institute of Neurological 

Disorders and Stroke

National Institutes of Health

6001 Executive Boulevard, Room 2118

Rockville, MD 20892

Phone: (301) 496-9964

Fax: (301) 402-2060

pn13w@nih.gov

Conception Nierras

Juvenile Diabetes Research 

Foundation International

120 Wall Street

New York, NY 10005

Phone: 1-800-533-CURE (2873)

Fax: (212) 785-9595

Charles Queenan

Juvenile Diabetes Research 

Foundation International

120 Wall Street

New York, NY 10005

Phone: 1-800-533-CURE (2873)

Fax: (212) 785-9595

John Ridge, MD

Program Officer

Diabetes and Autoimmunity Section 

of the Clinical Immunology Branch

National Institute of Allergy and 

Infectious Diseases

National Institutes of Health

6700B Rockledge Drive

9000 Rockville Pike

Bethesda, MD 20892

Phone: (301) 496-7104

Fax: (301) 402-2571

jr34g@nih.gov
DMICC ANNUAL REPORT 160 FY 2003

Sheryl Sato, PhD

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

6707 Democracy Boulevard, Room 6105

Bethesda, MD 20892

Phone: (301) 594-8811

Fax: (301) 480-3503

satos@extra.niddk.nih.gov

Peter Savage, MD

Director, Division of Epidemiology 

and Clinical Applications

National Heart, Lung and Blood Institute

National Institutes of Health

Rockledge 2, Room 8104

Bethesda, MD 20817

Phone: (301) 435-0421

Fax: (301) 480-1864

savagep@nhlbi.nih.gov

Salvatore Sechi, PhD

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

6707 Democracy Boulevard, Room 611

Bethesda, MD 20892

Phone: (301) 594-8814

Fax: (301) 480-2688

sechis@extra.niddk.nih.gov 

Lawrence Soler

Juvenile Diabetes Research 

Foundation International

120 Wall Street

New York, NY 10005

Phone: 1-800-533-CURE (2873)

Fax: (212) 785-9595

Allen Spiegel, MD

Director

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

Building 31, Room 9A52

31 Center Drive, MSC 2560

Bethesda, MD 20892

Phone: (301) 496-5877

Fax: (301) 402-2125

spiegela@extra.niddk.nih.gov

Ronnie Tepp

Juvenile Diabetes Research 

Foundation International

120 Wall Street

New York, NY 10005

Phone: 1-800-533-CURE (2873)

Fax: (212) 785-9595

Via Conference call

Frank Vinicor, MD

Director, Division of Diabetes Translation

Centers for Disease Control and Prevention

4770 Buford Highway North East, MSK-10

Atlanta, GA 30341

Phone: (770) 488-5000

Fax: (770) 488-5966

fxv1@cdc.gov 
APPENDICES
DMICC ANNUAL REPORT 163 FY 2003

NATIONAL DIABETES MELLITUS RESEARCH AND EDUCATION ACT, SECTION 429: 

Interagency Coordinating Committees

Sec.429. [285c—3] 

(a) For the purpose of —

(1) better coordination of the research activities of all the national research institutes relating to 

diabetes mellitus, digestive diseases, and kidney, urologic, and hematologic diseases; and

(2) coordinating those aspects of all Federal health programs and activities relating to such diseases 

to assure the adequacy and technical soundness of such programs and activities and to provide 

for the full communication and exchange of information necessary to maintain adequate 

coordination of such programs and activities;

the secretary shall establish a Diabetes Mellitus Interagency Coordinating Committee, a Digestive Diseases

Interagency Coordinating Committee, and a Kidney, Urologic, and Hematologic Diseases Coordinating Committee

(hereafter in this section individually referred to as a “Committee”).

(b) Each committee shall be composed of the Directors of each of the national research institutes and 

divisions involved in research with respect to the diseases for which the Committee is established,

the Division Director of the Institute for the diseases for which the Committee is established, the 

Chief Medical Director of the Veterans’ Administration,1 and the Assistant Secretary of Defense for

Health Affairs (or the designees of such officers) and shall include representation from all other

Federal departments and agencies whose programs involve health functions or responsibilities 

relevant to such diseases, as determined by the Secretary. Each Committee shall be chaired by the

Director of NIH (or the designee of the Director). Each committee shall meet at the call of the 

chairman, but not less often than four times a year.

(c) each Committee shall prepare an annual report for —

(1) the Secretary;

(2) the Director of NIH; and

(3) the Advisory Board established under section 430 for the diseases for which the Committee 

was established, detailing the work of the Committee in carrying out paragraphs (1) and 

(2) of subsection (a) in the fiscal year for which the report was prepared. Such report shall be 

submitted not later than 120 days after the end of each fiscal year.

1 The reference is deemed to be a reference to the Under Secretary for Health of the Department of Veteran Affairs.

See section 302 (e)(1) of Public Law 102-405(106) Stat. 1985 and section 10(4) of Public Law 100-527 (102 Stat.2641).

APPENDIX A
DMICC ANNUAL REPORT 165 FY 2003

DIABETES MELLITUS INTERAGENCY COORDINATING COMMITTEE

ROSTER OF MEMBERS (2003)

CHAIRMAN

Allen Spiegel, MD

Director

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health

Building 31, Room 9A52

31 Center Drive, MSC 2560

Bethesda, MD 20892

Phone: (301) 496-5877

Fax : (301) 402-2125

Email: spiegela@extra.niddk.nih.gov 

EXECUTIVE SECRETARY

Saul Malozowski, MD, PhD, MBA

Senior Advisor for Clinical Trials 

and Diabetes Translation

Division of Diabetes, Endocrinology, and 

Metabolic Diseases 

National Institute of Diabetes and 

Digestive and Kidney Diseases

National Institutes of Health 

6707 Democracy Blvd Room 679, MSC 5460 

Bethesda, MD 20892 

Phone: (301) 451-4683

Fax: (301) 480-3503 

Email: sm87j@nih.gov 

MEMBERS

Agency for Healthcare Research and Quality

Rosaly Correa-de-Araujo, MD, MSc, PhD

Senior Advisor on Women's Health 

John M. Eisenberg Building 

540 Gaither Road

Rockville, MD 20850

Phone: (301) 427-1550

Fax: (301) 427-1561

Email: rcorrea@ahrq.gov 

Center for Scientific Review

Ann A. Jerkins, PhD

Scientific Review Administrator

Metabolism Study Section

National Institutes of Health

Nutritional and Metabolic Sciences IRG

6701 Rockledge Drive, Room 6154, MSC 7892

Bethesda, MD 20892

Phone: (301) 435-4514

Fax: (301) 480-2065

Email: jerkinsa@csr.nih.gov 

APPENDIX B
DMICC ANNUAL REPORT 166 FY 2003

Centers for Disease Control and Prevention

Mark Eberhardt, PhD

Epidemiologist

National Center for Health Statistics

3311 Toledo Road

Hyattsville, MD 20782

Phone: (301) 436-5979, x142

Fax: (301) 436-8459

Email: mse1@cdc.gov

Frank Vinicor, MD

Director, Division of Diabetes Translation

4770 Buford Highway, North East, MSK-10

Atlanta, GA 30341

Phone: (770) 488-5000

Fax: (770) 488-5966

Email: fxv1@cdc.gov

Centers for Medicare and Medicaid Services

John P. Lanigan

Health Insurance Specialist

Office of Professional Relations

7500 Security Boulevard, C1-12-15 

Baltimore, MD 21244 

Phone: (410) 786-2312

Email: JLanigan@cms.hhs.gov 

Department of Health and Human Services

Susan J. Blumenthal, MD, MPA

US Assistant Surgeon General and 

Rear Admiral, US PHS

200 Independence Avenue, SW, Room 727H

Washington, DC 20201

Phone: (202) 260-2255

Fax: (202) 690-4631

Email: SBlumenthal@osophs.dhhs.gov

DHHS Office of Minority Health

Violet Woo, MS, MPH

Program Analyst

Department of Health and Human Services

1101 Wootton Parkway, Suite 500

Rockville, MD 20852

Phone: (301) 443-9923

Fax: (301) 443-8280

Email: vwoo@osophs.dhhs.gov

Food and Drug Administration

David Orloff, MD

Director, Division of Metabolic and 

Endocrine Drug Products

Parklawn Building, Room 14B-45

5600 Fishers Lane

Rockville, MD 20857

Phone: (301) 827-6430

Fax::(301) 443-9282

Email: orloffd@cder.fda.gov 

Health Resources and Services Administration

Suzanne Feetham, PhD, RN, FAAN

Senior Advisor, Office of Director, BPHC, Acting

Director Division of Clinical Quality

Bureau of Primary Health Care

4350 East West Highway, 11- 10 C1

Bethesda, MD 20814

Phone: (301) 443-2710

Fax: (301) 594-4072

SFeetham@hrsa.gov 
DMICC ANNUAL REPORT 167 FY 2003

Indian Health Service

Kelly Acton, MD, MPH

Director, National Diabetes Program

5300 Homestead Road, NE

Albuquerque, NM 87110

Phone: (505) 248-4182

Fax: (505) 248-4188

Email: kelly.acton@mail.ihs.gov 

National Center for Complementary and

Alternative Medicine

Marguerite Klein

Health Science Administrator

6707 Democracy Boulevard, Room 401

Bethesda, MD 20892

Phone: (301) 402-5860

Fax: (301) 480-3621

Email: kleinm@mail.nih.gov 

National Center for Research Resources 

Richard Knazek, MD

Medical Officer

Division of Clinical Research Resources

National Institutes of Health

6701 Democracy Boulevard

Democracy One, Room 910

Bethesda, MD 20892

Phone: (301) 435-0792

Fax: (301) 480-3661

richardk@ncrr.nih.gov 

National Center on Minority Health 

and Health Disparities

Jean L. Flagg-Newton, MD

Chief, Office of Research

National Institutes of Health

2 Democracy Plaza

6707 Democracy Boulevard, Suite 800

Bethesda, MD 20892

Phone: (301) 402-1366

Fax: (301) 402-7040

Email: flaggnej@od.nih.gov

National Eye Institute

Peter A. Dudley, PhD

National Institutes of Health

5635 Fishers Lane, Suite 1300, MSC 9300

Bethesda, MD 20892

Phone: (301)-451-2020

Fax: (301)-402-0528

pad@nei.nih.gov 

National, Heart, Lung and Blood Institute

Peter J. Savage, MD

Director, Division of Epidemiology 

and Clinical Applications

National Institutes of Health

Rockledge 2, Room 8104

Bethesda, MD 20817

Phone: (301) 435-0421

Fax: (301) 480-1864

Email: savagep@nhlbi.nih.gov
DMICC ANNUAL REPORT 168 FY 2003

National Human Genome Research Institute 

Christopher P. Austin, MD

Senior Advisor to the Director 

for Translational Research

National Institutes of Health

31 Center Drive

Building 31, Room 4B09

Bethesda, MD 20892

Phone: (301) 594-6238

Fax: (301) 402-0837

Email : austinc@mail.nih.gov

National Institute of Allergy and 

Infectious Diseases

John Ridge, MD

Program Officer

Diabetes and Autoimmunity Section 

of the Clinical Immunology Branch

National Institutes of Health

6700B Rockledge Drive 

Bethesda, MD 20892

Phone: (301) 496-7104

Fax: (301) 402-2571

Email: jr34g@nih.gov 

National Institute of Biomedical Imaging

and Bioengineering

Joan T. Harmon, PhD

Director, Office of Extramural Policy

National Institutes of Health

6707 Democracy Boulevard, Room 241

Bethesda, MD 20892

Phone: (301) 451-4776

Fax: (301) 480-4974

Email:harmonj@mail.nih.gov 

National Institute of Child Health and

Human Development

Gilman D. Grave, MD

Chief, Endocrinology, Nutrition and Growth Branch

Center for Research for Mothers and Children

National Institutes of Health

6100 Executive Boulevard; Suite 4B-11 

Bethesda, MD 20892

Phone: (301) 496-5593

Fax: (301) 480-9791

Email: gg37v@nih.gov

National Institute of Dental and 

Craniofacial Research

Patricia S. Bryant, PhD

Director, Behavior and Social Science Research

Division of Population and Health 

Promotion Sciences

National Institutes of Health

Building 45, Room 4AS-43A

Bethesda, MD 20892

Phone: (301) 594-2095

Fax: (301) 480-8322

Email: bryantp@de45.nidr.nih.gov

National Institute of Diabetes and 

Digestive and Kidney Diseases

Judith E. Fradkin, MD

Director, Division of Diabetes, Endocrinology 

and Metabolic Diseases

National Institutes of Health

Building 31, Room 9A27

31 Center Drive, MSC 2560

Bethesda, MD 20892

Phone: (301) 496-7349

Fax: (301) 480-6792

E-mail: jf58s@nih.gov
DMICC ANNUAL REPORT 169 FY 2003

National Institute of Environmental 

Health Sciences

Perry Blackshear, MD, DPhil

Director, Office of Clinical Research

National Institutes of Health

Post Office Box 12233

NIEHS, MD A2-05

RTP, NC 27709

Phone: (919) 541-4899

Fax: (919) 541-4571

Email: black009@niehs.nih.gov

National Institute of General Medical Sciences

Richard Anderson, MD, PhD

Program Director, Division of Genetics and

Developmental Biology

National Institutes of Health

Natcher Building, Room 2AS-25

45 Center Drive, MSC 6200

Bethesda, MD 20892

Phone: (301) 594-0943

Fax: (301) 480-2228

Email: andersor@nigms.nih.gov

National Institute of Mental Health

Peter Muehrer, PhD

Chief, Health and Behavioral Science

Research Branch

Division of Mental Disorders, Behavioral 

Research and AIDS

National Institutes of Health

6001 Executive Boulevard, Room 6189,

MSC 9615

Bethesda, MD 20892

Phone: (301) 443-4708

Fax: (301) 480-4415

Email: pmuehrer@mail.nih.gov

National Institute of Neurological Disorders

and Stroke

Audrey S. Penn, MD

Deputy Director

National Institutes of Health

31 Center Drive, Room 8A52

Bethesda, MD 20892

Phone: (301) 496-3167

Fax: (301) 496-0296

Email: ap101d@nih.gov

National Institute of Nursing Research

Nell Armstrong, PhD, RN

Program Director

National Institutes of Health

6701 Democracy Boulevard, Room 710

Bethesda, MD 20892

Phone: (301) 594-5973

Fax: (301) 480-8260

Email: armstrongn@nih.gov 

National Institute on Aging

Chhanda Dutta, PhD

Chief, Clinical Gerontology Branch

Geriatrics and Clinical Gerontology Program

National Institutes of Health

Gateway Building, Suite 3C-307

7201 Wisconsin Avenue

Bethesda, MD 20892

Phone: (301) 435-3048

Fax: (301) 402-1784

Email: cd23z@nih.gov
DMICC ANNUAL REPORT 170 FY 2003

National Institute on Alcohol Abuse 

and Alcoholism

Ricardo A. Brown, PhD

Program Director, Biomedical Research Branch

Division of Basic Research

National Institutes of Health

Willco Building, Room 402

6000 Executive Boulevard, MSC 7003

Bethesda, MD 20892-7003

Phone : (301) 443-2239

Fax : (301) 594-0673

Email: ricbrown@mail.nih.gov

National Institute on Deafness and Other

Communication Disorders

Baldwin Wong

Chief Science Policy and Planning Branch

National Institutes of Health

Building 31, Room 2C27

31 Center Drive

Bethesda, MD 20892

Phone: (301) 496-2426

Fax: (301) 402-2265

bw99s@nih.gov 

National Institute on Drug Abuse

Jag H. Khalsa, PhD

Acting Chief, Medical Consequences Unit

Center on AIDS and Other Medical 

Consequences of Drug Abuse (CAMCODA)

National Institutes of Health

6001 Executive Boulevard, Room 5098, MSC 9593

Bethesda, MD 20892-5953

Phone: (301) 443-1801

Fax: (301) 480-4544

jk98p@nih.gov 

National Library of Medicine

Elliot R. Siegel, PhD

Associate Director of Health Information

Programs Development

National Institutes of Health

8600 Rockville Pike

Bethesda, MD 20892

Phone: (301) 496-8834

Fax: (301) 496-4450

Email: siegel@nlm.nih.gov

Veterans Health Administration

Leonard M. Pogach, MD, MBA

Veterans Administration National 

Program Director, Diabetes

East Orange Veterans Affairs Medical Center

385 Tremont Avenue

East Orange, NJ 07018

Phone: (973) 676-1000, ext. 1693

Fax: (973) 395-7092

Email: Leonard.pogach@med.va.gov