DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH

Fiscal Year 2006 Budget Request

Witness appearing before the

House Subcommittee on Labor-HHS-Education Appropriations

Allen M. Spiegel, M.D., Director

National Institute of Diabetes and Digestive and Kidney Diseases

March 9, 2005

William Beldon, Deputy Assistant Secretary, Budget

Mr. Chairman and Members of the Committee:

I am pleased to present the Fiscal Year (FY) 2006 President\'s budget
request for the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) a sum of \$1,872,146,000, which includes \$150,000,000
for the Special Appropriation for Research on Type 1 Diabetes through
Sec. 330B of the Public Health Service Act. The NIDDK transfers some of
these funds to other institutes of the NIH and to the Centers for
Disease Control and Prevention (CDC). Adjusted for mandatory funds, this
is an increase of \$8,562,000 over the FY 2005 enacted level of
\$1,863,584,000 comparable for transfers proposed in the President\'s
request.

I appreciate the opportunity to testify on behalf of the NIDDK. Our
Institute supports research to combat a wide range of debilitating
chronic health problems, including diabetes and other endocrine and
metabolic diseases; digestive diseases; kidney and urologic diseases;
blood diseases; and obesity. Through vigorous support of
investigator-initiated research and Institute-initiated efforts, the
NIDDK will continue to elucidate the fundamental biology underlying
health and disease and to explore new strategies for disease diagnosis,
treatment, and ultimately, prevention.

FROM THE LABORATORY BENCH TO THE PATIENT'S BEDSIDE

In recent years, ever-advancing technologies have led to an explosion of
biomedical knowledge. It is imperative that scientists harness new
discoveries to improve medical care. Thus, in addition to supporting
critical basic and clinical research, the NIDDK is also bolstering
"translational" research, to accelerate the progression of scientific
discovery from basic to clinical studies to directly benefit patients.
In one stage of translational research, insights gained at the
laboratory "bench" spur the design of new strategies for prevention or
intervention, which investigators then test in clinical studies---at the
patient "bedside." In a second stage of translational research,
investigators explore ways to bring successful interventions and
lifesaving knowledge from the clinical research setting into the realm
of healthcare practice.

With the goal of directing NIDDK translational research investments to
enhance efforts on multiple diseases, I established a Trans-NIDDK
Translational Research Working Group to identify research obstacles and
opportunities. The Working Group charted the progression from basic to
clinical research to medical practice for a number of health conditions
to identify common themes for future research. These analyses were
considered by NIDDK's National Advisory Council; external advice was
also received at other scientific meetings.

By way of example, translational research relating to the assessment of
blood sugar (glucose) levels has greatly benefited diabetes care.
Scientists discovered that levels of a variant of the red blood cell
protein hemoglobin, called hemoglobin A~1c~ (HbA~1c~), correlate with
blood sugar levels. In the 1990s, a landmark NIDDK-supported clinical
trial demonstrated that people with type 1 diabetes can reduce the risk
of eye, kidney, and nerve complications by lowering their HbA~1c~ levels
through intensive treatment of blood sugar. As a result of this
research, target levels for HbA~1c~ were set, thus improving patient
care by encouraging medical practitioners to use a combination of
methods to better control blood sugar. This research further led to the
FDA's acceptance of the HbA~1c~ level as an end-point sufficiently
robust to define clinical benefit in clinical trials. "Biomarkers," such
as the level of HbA~1c~, can facilitate clinical trials and thus
stimulate the development of new therapeutic agents. Many new drugs for
diabetes have now been FDA-approved based on HbA~1c~ as an outcome.

In another example of successful bench-to-bedside research,
NIDDK-supported investigators elucidated the biological defect
responsible for the devastating inherited metabolic disease, MPS I;
discovered a naturally-occurring dog model for the disease; and tested a
potential therapy in dogs. Following clinical testing, this therapeutic
agent is now produced by industry and available on the market to treat
this disease. These two examples illustrate the critical role of NIH
investment in research from bench-to-bedside. Both also spanned several
decades from the initial basic research discoveries to clinical
application. Thus, a critical goal of NIDDK's new translational research
efforts is to accelerate this process.

In one planned translational research effort, the NIDDK will pursue the
development of new biomarkers. Examples of diseases or conditions for
which such biomarkers would be valuable include acute kidney failure,
liver and kidney fibrosis, type 1 diabetes, and insulin
resistance---which is associated with type 2 diabetes. The NIDDK will
also foster research on biomarkers for interstitial cystitis, including
the evaluation of a potential diagnostic marker that emerged from prior
NIDDK-funded research.

Among other translational research efforts, the NIDDK will strengthen
research to bring new non-invasive imaging techniques from the
laboratory to the clinical setting to enhance clinical research on
liver, pancreatic, kidney, and urologic diseases. The Institute will
also encourage the development of new animal models suitable for
preclinical testing of diagnostic, preventive, or therapeutic
interventions for diseases within NIDDK's mission. Although a wealth of
information about human biology has been and continues to be gleaned
from studies of mice and other animals, in many cases existing animal
models are insufficient for preclinical testing. Other translational
research efforts are capitalizing on fundamental knowledge about how
proteins assume their proper structures. This approach, informed by a
recent NIDDK-sponsored conference, will help propel the search for
therapies for cystic fibrosis and certain liver and kidney diseases,
which are caused by defects in protein "folding" or "processing."
Translational research promoted by the NIH Roadmap will synergize with
these NIDDK efforts to accelerate progress.

Insights gained from clinical observations can open new avenues for
basic research studies, which, in turn, will spur new clinical research
endeavors. Several NIDDK initiatives are fostering increased
collaboration between basic and clinical researchers, including support
for ancillary studies to major ongoing NIDDK clinical trials. Such
studies will also maximize the Institute's investment in these trials.
As part of our new efforts to enhance our research centers programs, the
NIDDK will encourage basic and clinical research partnerships to take
advantage of the opportunities of research centers.

In addition to the bench-to-bedside research just described, the NIDDK
is pursuing strategies to best translate successful clinical research
results from patient study volunteers to the public. These efforts
include, for example, translating the results of the Diabetes Prevention
Program (DPP) clinical trial, which demonstrated that people at high
risk for type 2 diabetes can dramatically reduce risk of disease onset
through modest weight loss and exercise. To promote these positive
findings, the NIDDK launched its campaign, *"Small Steps. Big Rewards.
Prevent Type 2 Diabetes,"* with tailored messages and materials
developed for ethnic groups at high risk for type 2 diabetes, older
adults, and a general audience. In parallel, the Institute is supporting
research demonstration and dissemination projects to explore new
strategies for effectively translating the DPP results, from clinical
trial to community. This research includes testing programs that target
different age groups and minority populations.

New translation efforts to combat kidney disease are building upon the
recent finding that even modestly-impaired kidney function increases
risk of cardiovascular disease and premature death. Avoiding these
devastating outcomes requires early awareness of kidney disease and
appropriate treatment. Critically important is detection of
deterioration in the kidneys' filtering capacity, the glomerular
filtration rate (GFR). While GFR is difficult to measure directly, it
can be estimated from routinely measured serum creatinine. The NIDDK's
National Kidney Disease Education Program (NKDEP) is thus encouraging
laboratories that measure serum creatinine to provide clinicians with
GFR values. The NKDEP recently launched an education campaign
emphasizing the importance of early detection and treatment, and
targeting this message to primary care providers and those at high risk
for kidney disease.

EXAMPLES OF BASIC AND CLINICAL RESEARCH ENHANCEMENTS

Underscoring a growing health crisis among our Nation's children, this
past year an NIDDK-supported pilot study of middle school students
uncovered high levels of the \"metabolic syndrome," which is a cluster
of health problems associated with obesity and increased risk for
diabetes and cardiovascular disease. To address the health threats posed
by obesity, we developed and published a *Strategic Plan for NIH Obesity
Research*. Informed by extensive input from scientific and lay experts,
the Strategic Plan was developed by the NIH Obesity Research Task Force.
Since its inception by the NIH Director, I have had the privilege of
co-chairing the Task Force with the NHLBI Director, with the aims of
synergizing and accelerating obesity research across the NIH. Consistent
with the goals of the *Strategic Plan*, the NIDDK is pursuing a
multifaceted obesity research agenda, from basic molecular
investigations to novel intervention studies to translational research.
For example, the NIDDK is spearheading a new trans-NIH initiative to
study how factors such as maternal weight during pregnancy can lead to
obesity in offspring. This research has important implications for
public health.

In the area of digestive diseases, the *Action Plan for Liver Disease
Research* has now been published. It was developed through NIDDK-led
efforts with broad external input from the research, professional, and
patient-advocacy communities. Examples of the many areas addressed by
the *Action Plan* include developing or improving therapies for
hepatitis C; developing tools for early liver cancer detection; and
research on living donor liver transplantation. The *Action Plan* will
direct new liver disease research; the NIDDK will also continue major
ongoing clinical studies on hepatitis C; biliary atresia, a disease that
strikes children; and non-alcoholic steatohepatitis, a fatty liver
disease.

The *Action Plan for Liver Disease Research* is part of a larger
planning process for research on digestive diseases, which have an
enormous burden on the U.S. population. For inflammatory bowel disease,
external advice received in previous planning efforts will continue to
inform the NIDDK research agenda. New planning efforts will aim to
strengthen research on irritable bowel syndrome and other functional
gastrointestinal disorders, which are debilitating and highly prevalent
but not well understood. Following focused planning efforts relevant to
gastroparesis, the NIDDK will establish a new clinical research
consortium to study this debilitating syndrome of nausea, vomiting,
bloating, and other symptoms which complicates diabetes and other
diseases.

In the areas of kidney and urologic diseases, in addition to the efforts
described earlier, the NIDDK will encourage partnerships to pursue
promising new therapies for polycystic kidney disease, and will launch a
new clinical intervention study of children with vesicoureteral reflux,
a bladder condition which can impair kidney function.

I have highlighted today examples of NIDDK's many and diverse research
plans and efforts. These reflect our strong commitment to improving
human health.

Thank you, Mr. Chairman. I would be pleased to answer any questions that
the Committee may have.

**DEPARTMENT OF HEALTH AND HUMAN SERVICES**

**National Institutes of Health**

**National Institute of Diabetes and Digestive and Kidney Diseases**

**Biographical Sketch**

**NAME:** Allen M. Spiegel, M.D.

**POSITION:** Director, National Institute of Diabetes and Digestive and
Kidney Diseases

**BIRTHPLACE :** Germany

**DATE:** May 18, 1946

**EDUCATION:** B.A., Columbia College, 1967

M.D., Harvard Medical School, 1971

**EXPERIENCE:**

1999-present Director, National Institute of Diabetes and Digestive and
Kidney Diseases, NIH

1990-1999 Director, Division of Intramural Research, National Institute
of Diabetes and Digestive and Kidney Diseases, NIH

1993-present Chief, Metabolic Diseases Branch, National Institute of
Diabetes and Digestive and Kidney Diseases, NIH

1988-1993 Chief, Molecular Pathophysiology Branch, Metabolic Diseases
Branch, National Institute of Diabetes and Digestive and Kidney
Diseases, NIH

1985-1988 Chief, Section on Molecular Pathophysiology, Metabolic
Diseases Branch, National Institute of Arthritis, Diabetes, and
Digestive and Kidney Diseases, NIH

1977-1984 Senior Investigator, Metabolic Diseases Branch, National
Institute of Arthritis, Metabolism, and Digestive Diseases, NIH

1973-1976 Fellow, NIH Endocrinology Training Program, Clinical
Associate, Metabolic Diseases Branch (Dr. G. D. Aurbach, Chief),
National Institute of Arthritis, Metabolism, and Digestive Diseases, NIH

1971-1973 Intern and Assistant Resident in Medicine, Massachusetts
General Hospital, (Dr. Alexander Leaf, Chief)

**HONORS AND AWARDS:**

1966 - Elected to Phi Beta Kappa

1967 - B.A. Summa Cum Laude

1971 - Elected to Alpha Omega Alpha

1971 - M.D. Cum Laude

1988 - Outstanding Service Medal - U.S. Public Health Service

1990 - Meritorious Service Medal - U.S. Public Health Service

1990 - Jacobaeus Prize - Nordisk Insulin Foundation

1993 - Plenary Lecturer - Japan Endocrine Society

1993 - Aurbach Memorial Lecturer - American Society for Bone and Mineral
Research

1994 - Harrison Memorial Lecturer - Endocrine Society of Australia

1996 - Komrower Memorial Lecturer - Society for the Study of Inborn
Errors of Metabolism

1998 - Edwin B. Astwood Lecture Award - Endocrine Society (U.S.A.)

**PROFESSIONAL ORGANIZATIONS:**

American Federation for Clinical Research

The Endocrine Society

American Society for Bone and Mineral Research

American Society for Clinical Investigation

American Society for Biochemistry and Molecular Biology

Association of American Physicians

Institute of Medicine of the National Academy of Sciences

**LICENSURE AND CERTIFICATION:**

Diplomate American Board of Internal Medicine, 1974

Board Certified in Endocrinology, 1975

Licensed in Medicine, Maryland

**Number range CHAPTERDepartment of Health and Human Services**

**Office of Budget**

**William R. Beldon**

Mr. Beldon is currently serving as Deputy Assistant Secretary, Budget in
the Department of Health and Human Services. He has been a Division
Director in the Budget Office for sixteen years, most recently as
Director of the Division of Discretionary Programs. Mr. Beldon started
in federal service as an auditor in the Health, Education and Welfare
Financial Management Intern program. Over the course of more than 30
years in the Budget Office, Mr. Beldon has held Program Analyst, Branch
Chief and Division Director positions. Mr. Beldon received a Bachelor's
Degree in History and Political Science from Marshall University and
attended the University of Pittsburgh where he studied Public
Administration. He resides in Fort Washington, Maryland.