# Presentation: 895729

## Research Highlights from the National Institute of Diabetes and Digestive and Kidney Diseases

- Griffin P. Rodgers, M.D., M.A.C.P.
- Director

**Notes:**
The NIDDK conducts and supports basic and applied research and provides leadership for a national program in:
Diabetes, Endocrinology, and Metabolic Diseases;
Digestive Diseases and Nutrition; and
Kidney, Urologic, and Hematologic Diseases.
The research mission of the NIDDK was defined by the U.S. Congress when it established the Institute: “The general purpose of the National Institute of Diabetes and Digestive and Kidney Diseases...is the conduct and support of research, training, health information dissemination, and other programs with respect to diabetes mellitus and endocrine and metabolic diseases, digestive diseases and nutritional disorders, and kidney, urologic, and hematologic diseases.”

## Biomedical Research Programs

**National Institute of Diabetes, Digestive and Kidney Diseases**
**Biomedical Research Programs**

**Basic Research**

**Applied Research**

**Clinical Investigations and Trials**

**Demonstration and Education Research**

**Knowledge Acquisition**

**Knowledge Validation**

**Knowledge Transfer**

**Knowledge Dissemination**

**Notes:**

The NIDDK engages in and supports biomedical research ranging from basic studies of fundamental processes, to clinical trials of novel therapeutic agents and strategies, to the translation and dissemination of health information to health care providers, patients, and the public.  Efforts include:

Identification of health problem
Epidemiologic & basic research to identify  potential risk factors, mechanisms, & influences
Clinical trials to determine efficacy of novel therapies on health outcomes
Translation of research from the bench to the bedside, and back
Dissemination of information through national education programs

The Institute aims to move advances in basic science, achieved at the “bench,” into trial of novel therapies in patients at the “bedside.”  The NIDDK also strives to use knowledge gained during such trials to fuel future laboratory studies.

Goals are better diagnosis and treatment, cure, and prevention. NIH role in achieving goals is to support discovery of new knowledge and to see that knowledge disseminated into practice.

## Organizational Structure of NIDDK’s Three Extramural Scientific Divisions

**Organizational Structure of NIDDK’s Three Extramural Scientific Divisions**

**NIDDK**

**KUH**

- Division of Kidney,
- Urologic, and
- Hematologic
- Diseases

**DDN**

- Division of
- Digestive Diseases
- and
- Nutrition

**DEM**

- Division of Diabetes,
- Endocrinology,
- and
- Metabolic Diseases

**Notes:**
The three extramural scientific divisions support research programs at facilities that include diabetes, endocrinology, metabolic and genetic diseases; digestive diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases. 

In addition to these extramural Divisions, the Division of Intramural Research conducts research and training within the Institute's laboratories and clinical facilities in Bethesda, Maryland, and at the Phoenix Epidemiology and Clinical Research Branch in Arizona. 

The Division of Extramural Activities provides administrative support and overall coordination.  A fifth division, the Division of Nutrition Research Coordination, coordinates government nutrition research efforts across the NIH and with other Federal agencies.

## A Paradigm of NIDDK’s Integrated Research Programs

- Obesity

- Type 2
- Diabetes

- Kidney
- Disease

- Type 1
- Diabetes

**Notes:**
In this presentation, I’d like to use obesity, type 2 diabetes, and kidney disease, to illustrate how the NIDDK works with the research community to investigate diseases, how they are connected, and approaches that we can take to address each one.  I also want to talk about how information we’ve learned from type 1 diabetes has provided important insights into ways to delay or prevent the complications of diabetes, such as kidney disease.

Obesity is present at epidemic levels in the U.S. and many other nations.  Being overweight or obese puts individuals at increased risk of developing a number of diseases.  One of the more common diseases seen in obese people is type 2 diabetes, the incidence of which is also rising rapidly in the U.S.  Type 2 diabetes is, in turn, the leading cause of kidney failure in the U.S.  The NIDDK has vigorous research programs targeting each of these three conditions; let’s start by looking at obesity. 

## Health Complications of Obesity

**Phlebitis**
- venous stasis

**Coronary heart disease**

**Pulmonary disease**
- abnormal function
- obstructive sleep apnea
- hypoventilation syndrome

**Gall bladder disease**

**Gout**

**Diabetes**

**Osteoarthritis**

**Nonalcoholic fatty liver disease**
- steatosis
- steatohepatitis
- cirrhosis

**Hypertension**

**Dyslipidemia**

**Cataracts**

**Skin**

**Pancreatitis**

**Cancer**
- breast, uterus, cervix, prostate, kidney
- colon, esophagus, pancreas, liver

**Gynecologic abnormalities**
- abnormal menses
- infertility
- polycystic ovarian syndrome

**Stroke**

**Health Complications of Obesity**

**Idiopathic intracranial **
**hypertension**

**Notes:**
Obesity results from an imbalance in caloric intake relative to caloric expenditure.  This imbalance causes fat to accumulate.  Researchers usually define overweight and obesity in terms of an individual’s body mass index, or BMI.  BMI is calculated by dividing a person’s weight in kilograms by his or her height in meters squared [kg/m2].  A person with a BMI over 25 is classified as overweight, while a person with a BMI of 30 or above is considered obese.

Overweight is defined somewhat differently in children and adolescents. After BMI is calculated, it is plotted on growth charts -- based on national surveys compiled before the recent increase in obesity -- to obtain a percentile ranking. If a child’s BMI is above the 85th percentile for his or her age, then he or she is at risk of becoming overweight. If a child’s BMI is above the 95th percentile, the child is overweight.  There is no generally accepted definition for obesity, as distinct from overweight, in this age group.

Obesity is a problem in the U.S. for two main reasons.  The first is that a large number of health problems are associated with obesity.  They include high blood pressure, cardiovascular disease, stroke, arthritis, and many others.  The multitude of co-morbidities associated with obesity reflects the complexity and diversity of systems that contribute to energy balance. Obesity is also associated with several diseases within the research mission of the NIDDK, including nonalcoholic fatty liver disease and type 2 diabetes.

Image modified from one appearing in National Geographic magazine.

## Obesity Trends Among U.S. Adults

- <date/time>

- <footer>

- No Data             <10%            10-14%           15-19%            20-24%            ≥25%

- 2004

**Notes:**
The second reason obesity is a big problem in the U.S. is that it is growing at an alarming rate.  A quick look at these maps is all it takes to realize the scope of the obesity problem.  Between 1991 and 2004, there was a dramatic increase in the number of people who were obese, and in many American states in 2004, more than a quarter of residents were obese.  In fact, the problem may be even worse than it appears in these maps.  Data published in 2006 indicate that 32 percent of adults are obese, and, ominously, 17 percent of children are overweight.

What is responsible for this sudden increase in the number of obese people in the U.S.? Obesity most likely results from an interplay between genes and the environment.  However, the recent explosion in the prevalence of obesity has occurred too quickly to be explained solely by changes in our genes. One hypothesis is that, in the past, humans who were able to accumulate fat when food was plentiful were better able to survive during times of food scarcity. Now, however, in the U.S. and many other countries, food is plentiful and foods that are high in calories but often low in nutritional value tend to be relatively inexpensive.  Furthermore, most people engage in far less physical activity than did previous generations.  Ironically, the ability to accumulate fat during times of plenty – which was originally thought to confer a benefit – has become a detriment to our health.  Research supported by the NIDDK has led to improved understanding of the factors contributing to this complex condition.

Source: Behavioral Risk Factor Surveillance System, CDC. 
Ogden et al, JAMA 295:1549-1555, 2006.

## Obesity: Gene/Environment Interactions

**Obesity: Gene/Environment Interactions**

**Current environment**

**Past environment**

- Genetic susceptibility

- Adipocity phenotype
- (e.g., body mass index)

**Notes:**
What is responsible for this sudden increase in the number of obese people in the U.S.? Obesity most likely results from an interplay between genes and the environment.  However, the recent explosion in the prevalence of obesity has occurred too quickly to be explained solely by changes in our genes. One hypothesis is that, in the past, humans who were able to accumulate fat when food was plentiful were better able to survive during times of food scarcity. Now, however, in the U.S. and many other countries, food is plentiful and foods that are high in calories but often low in nutritional value tend to be relatively inexpensive.  Furthermore, most people engage in far less physical activity than did previous generations.  Ironically, the ability to accumulate fat during times of plenty – which was originally thought to confer a benefit – has become a detriment to our health.  Research supported by the NIDDK has led to improved understanding of the factors contributing to this complex condition.

G.S. Barsh, I.S. Farooqi, S. O’Rahilly. Nature 404: 644, 2000

## Slide 8

**Notes:**
Access to relatively inexpensive, high-caloric, low nutrient foods

Diminished physical activities at home, school and work

Built environment (aspects of community design that may influence activity levels or diet).

## Molecular Causes of Obesity

**mTOR signaling regulates food intake**

**Serotonin regulates melanocortin 4 neurons to modulate food intake**

**Cota et al., 2006.  **_**Science**_** 312: 927-930.**

**Heisler et al., 2006.  **_**Neuron**_** 51:239-249.**

**Notes:**
Anorectic signals--amino acids, the hormone leptin, and re-feeding--increase hypothalamic mTOR signaling, which decreases food intake. Leptin and refeeding also decrease hypothalamic AMPK.  mTOR is inhibited by AMPK-dependent mechanisms in vitro, so reciprocal interaction might exist between hypothalamic mTOR and AMPK. 
Serotonin (5-hydroxytryptamine, 5-HT) regulate food intake by modulating release of agonists and antagonists of the melanocortin 4 receptor, a core component of the central circuitry controlling body weight homeostasis. 

## Gut Microflora and Obesity

***Nature, December 2006 ***

**Notes:**
In addition to research on neural controls that influence feeding behavior, we are also beginning to appreciate how the mix of microbes that inhabit the human GI tract contributes to how effectively we absorb the nutrients we ingest, and therefore, plays an important role in the propensity toward obesity in some or malnourishment in others.
This exciting area of research was featured in a recent issue of the journal Nature, which highlighted work showing that certain gut microbes are predominant in obese mice and humans, versus lean controls.  In fact, the bacteria from obese individuals had an increased capacity for extracting energy from the diet.
These studies suggest that gut microbes play a critical and long-overlooked role in obesity, opening up some exciting opportunities for potential therapies to address the obesity epidemic.

## A Paradigm of NIDDK’s Integrated Research Programs

- Obesity

- Type 2
- Diabetes

- Kidney
- Disease

- Type 1
- Diabetes

**Notes:**
Obesity is a major driving force in the development of type 2 diabetes.  Type 2 diabetes was formerly known as “adult-onset” diabetes.  As we shall see, though, it is no longer only adults who are at risk of developing this disease.  I’d also like to talk about some of the things we’ve learned about the importance of managing diabetes from studies of type 1 diabetes.  Both forms of the disease share complications, so research into type 1 is relevant to type 2 as well.

## Estimates of Diagnosed Diabetes Among Adults in the U.S.

- <date/time>

- <footer>

- No Data                 <4%             4-4.9%            5-5.9%                ≥6%

**Estimates of Diagnosed Diabetes Among Adults in the U.S.**

**Notes:**
Diabetes has been increasing in the U.S. in recent years.  Between 1994 and 2004, there was a dramatic increase in the number of people with diagnosed diabetes in the U.S.  Over the past 25 years, the prevalence of diabetes has more than doubled. It is thought that the increase in diabetes is due largely to an increase in type 2 diabetes that is being driven by three major trends in the U.S. population:
An aging population
A growing number of racial and ethnic minorities
A dramatic increase in overweight and obesity – serious risk factors for developing the disease

Statistics related to diabetes
20.8 million Americans (7 percent of the U.S. population) have diabetes
90-95 percent of cases are type 2 diabetes
Minorities are disproportionately affected by type 2 diabetes
1 in 3 Americans born in 2000 is predicted to develop diabetes during his or her lifetime (for Hispanic females: 1 in 2)

Sources: CDC National Diabetes Surveillance System, 2005; Diabetes: Disabling, Deadly, and on the Rise, CDC, 2006; World Health Organization, Diabetes Care 28: 2130-2135, 2005.

## Diagnosed Diabetes in the U.S. 

- 0

- 10

- 20

- 30

- 40

- 50

- 1960

- 1970

- 1980

- 1990

- 2000

- 2010

- 2020

- 2030

- 2040

- 2050

**People (millions)**

**Year**

**Diagnosed Diabetes in the U.S. **
- Diagnosed (1960-2004) and
- Projected Diagnosed (2005-2050) Cases

- Diagnosed cases

- Projected
- diagnosed cases

**Notes:**
The problem of diabetes in the U.S. is likely to be even worse than it appears  This graph reflects only diagnosed cases of diabetes.  But, 1 in 3 people with diabetes is unaware that he or she has the disease.  If you do not know that you have diabetes and you are not being treated, your diabetes is not controlled, and you are at even greater risk of developing complications such as heart disease, blindness, or kidney disease.

The uptick in diagnosed cases between 2000-2004 may reflect an increase in the number of overall cases, possibly due to under-representation of Hispanics in earlier data sets, or it may reflect improvements in diagnosing diabetes in previously undiagnosed individuals.

Predictions of future cases of diagnosed diabetes paint a sobering picture.  The Centers for Disease Control and Prevention project that, by 2050, nearly 50 million Americans will have been diagnosed with diabetes.

Source: Data for 1960-2004 from the National Health Interview Survey, NCHS, CDC. Projected data for 2005-2050 from Narayan KMV, et al, Diabetes Care 29:2114-2116, 2006.

## Results from the Diabetes Prevention Program Substantial Reduction in Diabetesin All Race-Ethnic Groups

**Notes:**
As grim as the future may look, there is some good news to report regarding type 2 diabetes.  NIH research has shown that type 2 diabetes can be delayed or prevented.  This figure depicts disease development in the different racial and ethnic groups in the landmark Diabetes Prevention Program (DPP) clinical trial. The DPP compared three approaches -- lifestyle modification, treatment with metformin, and standard medical advice -- in 3,234 overweight people at high risk of developing diabetes. 

Patients who received standard medical advice and a sugar pill (placebo) developed diabetes at the highest rate (red bars).  Patients in the metformin group also developed diabetes, but the overall rate was about 31 percent less than in the placebo group (yellow  bars).  Finally, the lifestyle intervention group, the individuals who lowered their caloric intake and walked about 30 minutes per day 5 times a week, showed the most dramatic improvement, with an overall 58 percent decrease of diabetes cases compared to placebo (blue bars). These improvements were seen across all racial and ethnic groups, and in participants of all ages.  

This study provides hope to all those prone to develop type 2 diabetes because it demonstrates that small changes in lifestyle could delay or prevent this disease. The NIDDK is currently following DPP participants to explore the durability of the interventions in preventing or delaying type 2 diabetes and cardiovascular disease.  We are also vigorously disseminating the prevention message of the DPP, with the hope that more individuals will also benefit from these lessons learned.  

## Stages in the History of 

- Preclinical
- state

- Normal

- Pre-
- diabetes

- Clinical
- disease

- Type 2
- Diabetes

**Disability**
**Death**

- Complications

- Complications

**Primary**
**Prevention**

**Stages in the History of **
**Type 2 Diabetes**

**54,000,000**

**20,800,000**

**BARI 2D**

**ACCORD**
**LookAHEAD**

**DPPOS**

**HEALTHY**

**Secondary Prevention**

**Tertiary Prevention**

**TODAY**

**Notes:**
NIH has a comprehensive clinical research program to address major question about the prevention and management of diabetes and its complications.  All trials have a significant cost effectiveness component to address issue of how best to spend limited resources to reduce the burden of diabetes.  Highlights of ongoing efforts are presented here.
Importantly DPP has shown that not only can lifestyle change prevent or delay development of type 2 diabetes, it can even reverse pre-diabetes in many individuals.  DPPOS will assess the durability of these effects and whether in addition to slowing progression toward diabetes, CVD risk is reduced.
Diabetes in particularly devastating in children in whom the longer duration of exposure to diabetes increases the risk of complications and childhood onset diabetes can dramatically reduce life expectancy, as shown in a recent study of the Pimas.
Efforts are underway both to prevent the development of risk factors for diabetes in a middle school based study (HEALTHY) and to learn how to best treat the newly emerging problem of type 2 diabetes in children (TODAY).
Two thirds of deaths from diabetes are due to CVD and studies are looking at optimal control of diabetes and associated blood pressure and lipid disorders for prevention of CVD (ACCORD) as well as whether investment of resources in weight loss after onset of diabetes will yield reduced CVD (LookAHEAD).  Other studies (BARI 2D) are comparing approaches to treat people with diabetes who have established CVD.      
These studies will provide evidence about which therapies yield the best results and a basis for future public health efforts.  

## Intensive Treatment Reduces Risk of Cardiovascular Disease in 

**0.00**

**0.02**

**0.04**

**0.06**

- Cumulative Incidence of Nonfatal Heart Attack, Stroke, or Death from Cardiovascular Disease

**Years Since Entry to Study**

**Conventional**

**Intensive**

**0       1       2       3       4        5        6       7        8       9       10     11     12     13      14      15     16     17     18     19      20     21**

**Intensive Treatment Reduces Risk of Cardiovascular Disease in **
**People with Type 1 Diabetes**

*Figure adapted from *N Engl J Med* 353: 2643-2653, 2005.*

**Notes:**
Why is it so important to closely control blood sugar levels? 
NIDDK research has shown that close control of blood sugar can dramatically prevent or delay life-threatening disease complications, including diabetic kidney, nerve, eye, and heart disease. 
This data is from a long-term study that has been supported in part by the Special Funding Program. Recent data has shown that the risk of the first occurrence of nonfatal heart attack, stroke, or death from cardiovascular disease was reduced 57 percent with intensive treatment, as compared with conventional treatment.
Because heart disease is the primary cause of death of type 1 diabetes patients, this very important result underscores the importance of closely controlling blood sugar levels to prevent this complication. 

## Continuous Glucose Monitoring

- DirecNet: Testing Continuous Glucose Monitors in Children

**Notes:**
Continuous glucose monitors let patients see their blood sugar level at any time without always having to do a finger stick.
The Diabetes Research in Children Network, also supported by the Special Program, is studying how advances in technology can be used to improve the management of type 1 diabetes in children and adolescents. Network plays an important role in independently testing the devices in children.
The network is also using devices to develop a better understanding of dangerous low blood sugar episodes.  Example: daytime exercise can increase nocturnal hypoglycemia.
These devices can help patients better manage their disease and reduce need for finger sticks and for interruptions in sleep.  

## External Closed-loopDevelopment System 

- Sensor signals transmitted to a laptop computer that displays the sensor glucose and calculates rate of insulin delivery

- Rate of insulin delivery is transmitted to the insulin pump

**Notes:**
Next step after continuous monitoring is to link the monitor to an insulin delivery device to create a closed loop that frees patients from constant attention to blood sugar control.  
Currently prototypes being tested in in patients.  
Relevant not just to type 1 but also to management of inpatient diabetes.  One quarter of hospitalized patients have DM.  Evidence in ICU studies that improved glucose control can reduce infection, shorten hospitalization and improve outcomes. Closed loop may be useful not only for T1D but for inpatient DM management and insulin requiring type 2.

## Islet Imaging– a Window on Diabetes

- Images courtesy of Dr. Alvin Powers and Marcella Brissova

**Islet Imaging– a Window on Diabetes**

**Notes:**
The ability to see insulin-producing beta cells within the body may prove invaluable in terms of diagnosing and managing diabetes, and could help researchers better understand the life cycle of these cells and how they are damaged in this disease.  
The problem is complex, because beta cells are one of several cell types in the islet, and represent only a small fraction of the total cells in the pancreas.  
On the left, a mouse was transplanted with 1,000 islet equivalents of human islets expressing a luminescent marker. Noninvasive, bioluminescence imaging was performed on the anesthetized mouse, and the transplanted islets could be easily visualized. 
In the image of a human islet on the right, the insulin-producing cells are stained green, two other cell types are stained blue or red.  (Other colors result when these three basic colors overlap in the three-dimensional image.) 

## Genetic Background Affects  the Phenotype of

- <date/time>

**Genetic Background Affects  the Phenotype of**
**IR/IRS-1 Double Heterozygous Knockout Mice**

**0**

**20**

**40**

**60**

**80**

**100**

**Prevalence of Diabetes (%)**

**Age (months)**

**0            2     4          6  **

***C57Bl/6J***

**DH**

**Wt**

**0          2           4          6  **

***129/Sv***

**DH**

**Wt**

**Age (months)**

- Due to differences in Insulin action, not insulin secretion.
- Genome-wide scan has identified 4 loci on 3 chromosomes which contribute to these phenotypic differences.

## Environmental Modifiers of Diabetes in NOD Mice

**Geography**

**Virus Infection**

**Diet**

**0**

**20**

**40**

**60**

**80**

**100**

**Percent Mice with Diabetes**

**Japan**

**Bar Harbor**

**Edmonton**

**LCMV-Infected**

**Control**

**Germ-Free**

**Protein-free**

**Control Diet**

**Yeast + OG96**

## Research on Causes ofType 1 Diabetes 

- Identifying genetic factors and environmental triggers
- T1D Genetics Consortium: pooling data from families to find T1D genes
- The Environmental Determinants of Diabetes in the Young (TEDDY): following newborns until age 15 to find disease triggers
- Also may provide insights into causes of celiac disease

**Notes:**
What other research is in the pipeline?
Here are a few examples of long-term research efforts that are feeding into the pipeline and have the potential to revolutionize disease prevention and treatment strategies. 
The Type 1 Diabetes Genetics Consortium is working together to pool data from 2,800 families with 2 or more siblings with T1D in order to find disease genes.
Knowing which genes are important in disease can lead to new ways to prevent or treat type 1 diabetes. 
The Environmental Determinants of Diabetes in the Young, or TEDDY, is a long-term effort that is enrolling newborns and following them until they are 15 years old in order to find environmental factors that trigger disease (or protect against the disease). 
This knowledge would be tremendously important for coming up with ways to prevent the disease. 
For example, if a virus was found to trigger disease, then perhaps a vaccine could be developed to help prevent it. 
In addition, TEDDY may provide key insights on environmental causes of celiac disease, which is an autoimmune disease which has overlapping genetic susceptibility with type 1 diabetes.  In celiac disease, gluten—a major protein in wheat, rye, and barley—triggers an immune response that damages the small intestine and interferes with the absorption of nutrients. Celiac disease is estimated to affect 1% of the US population, so information we gain on this disease through TEDDY has the potential to benefit many people. 

## A Paradigm of NIDDK’s Integrated Research Programs

- Obesity

- Type 2
- Diabetes

- Kidney
- Disease

- Type 1
- Diabetes

**Notes:**
One of the devastating complications of diabetes is kidney damage.  Early kidney disease has no symptoms, and can progress to kidney failure with little or no warning if left undetected.  Chronic kidney failure – so-called “end-stage renal disease” or ESRD -- occurs when the kidneys are no longer able to filter toxins from the blood.  People with ESRD must receive either hemodialysis or a kidney transplant to survive. Diabetes is the number one cause of ESRD in the U.S. There are other kidney and urologic complications of being overweight and/or having diabetes, as we shall see.

## End-stage Renal Disease in the U.S. Number of Patients per Million Population

**1993**

**2003**

**Notes:**
These maps show the distribution of people with end-stage renal disease in the U.S. in 1993 and 2003. The prevalence of ESRD has risen dramatically in the past several years.  However, there has been some recent, encouraging news that incidence rates are stabilizing, at least among some populations.

This data is collected by the U.S. Renal Data System, or USRDS. The USRDS is a national data system that collects, analyzes, and distributes information about end-stage renal disease (ESRD) in the United States. The USRDS is funded directly by the NIDDK in conjunction with the Centers for Medicare & Medicaid Services. 

Statistics for ESRD (for CY 2004)
Prevalence: 472,099 patients were undergoing treatment
Mortality: 84,252 deaths in patients undergoing treatment for ESRD
Primary cause:
Diabetes: 45,871
High blood pressure: 28,132
Primary treatment:
Dialysis: 335,963 patients received dialysis
Kidney Transplant: 16,905 performed
Minorities are disproportionately affected

Note: Maps indicate December 31 point prevalent ESRD patients; rates adjusted for age, gender, and race. 

## End-stage Renal Disease in the U.S. Adjusted Incident Rates & Annual Percent Change 

**Notes:**
However, we do have some good news to report about ESRD.  Recently there has been a leveling off in the rate of new cases of ESRD.  The green bars in this graph represent the rate of ESRD per million people in the U.S.  The blue lines represent the percent change in ESRD from the previous year.  

The leveling of ESRD rates has occurred despite demographic factors -- such as increased diabetes and aging of the population -- that would tend to increase rates of ESRD.  

Credit for these recent gains likely goes to clinical strategies proven in the 1990s to significantly delay or prevent kidney failure.  These include the use of angiotensin-converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs), which lower protein in the urine and are thought to directly prevent injury to the kidneys’ blood vessels; as well as careful control of diabetes and blood pressure.  NIH research has demonstrated the value of these approaches in clinical trials.  However, the overall improvement in the ESRD landscape is not seen in all Americans with the disease.

Rates adjusted for age, gender, & race.  US Renal Data System 2005 Annual Report.

## Incident Diabetic End-stage Renal Disease in the U.S.Age 20 to 29 Years

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

- 1980

- 1981

- 1982

- 1983

- 1984

- 1985

- 1986

- 1987

- 1988

- 1989

- 1990

- 1991

- 1992

- 1993

- 1994

- 1995

- 1996

- 1997

- 1998

- 1999

- 2000

- 2001

- 2002

- 2003

- Year

- Per million population

- Caucasian

- African American

**Notes:**
This graph illustrates the magnitude of the problem we still face in combating ESRD in the U.S.  While incidence is dropping among Caucasians between the ages of 20 and 29, it continues at extremely high levels among African Americans in this age group.  NIDDK-supported research programs are aimed at understanding the reasons for this disparity and closing this gap.

Rates adjusted for age, gender, & race.  US Renal Data System 2005 Annual Report

## Impact of Overweight and Obesity on Kidney Failure

- Adjusted Relative Risk for ESRD
- (Logarithmic Scale)

- 1.00

- 10.0

- 0.1

- 1.00

- Adjusted relative risk for end-stage renal disease (ESRD)
- by body mass index (BMI).

- <18.5 kg/m2

- 18.5-24.9 kg/m2

- 30.0-34.9 kg/m2

- ≥40 kg/m2

- 25.0-29.9 kg/m2

- 35.0-39.9 kg/m2

**Notes:**
In an analysis of data from thousands of adults, researchers found that the more excess weight people carried, the greater the risk for kidney failure, a serious condition requiring a kidney transplant or life-long dialysis.  The risk associated with excess weight existed even among those who did not have diabetes or high blood pressure at the beginning of the study; both of these conditions are also known risk factors for kidney disease.  One possible explanation for these findings is that those who were carried more excess weight may have subsequently developed diabetes or high blood pressure, which in turn led to kidney failure.  Alternatively, excess weight may also lead to kidney failure through other mechanisms. High BMI is a common, strong, and potentially modifiable risk factor for ESRD.

Source: Hsu CY, McCulloch CE, Iribarren C, Darbinian J, and Go AS:  Body mass index and risk for end-stage renal disease.  Ann Intern Med 144:  21-28, 2006.

## Weight-control Information Network

- WIN produces, collects, and disseminates materials on obesity, weight control, and nutrition.

**Weight-control ****Information Network**

## National Diabetes Education Program

- The National Diabetes Education Program (NDEP) is a federally funded program sponsored by the National Institutes of Health and the Centers for Disease Control and Prevention and includes over 200 partners at the federal, state, and local levels, working together to reduce the morbidity and mortality associated with diabetes.

## National Kidney DiseaseEducation Program

- The National Kidney Disease Education Program (NKDEP) is an initiative of the National Institutes of Health, designed to reduce the morbidity and mortality caused by kidney disease and its complications.

## NIDDK Core Missions

- Maintain a vigorous investigator-initiated
-  research portfolio
- Foster exceptional research training and
-  mentoring opportunities
- Preserve a stable pool of talented new
-  investigators
- Support pivotal clinical studies and trials
- Ensure knowledge dissemination through
-  outreach and communications

**Notes:**
The NIDDK engages in and supports biomedical research ranging from basic studies of fundamental processes, to clinical trials of novel therapeutic agents and strategies, to the translation and dissemination of health information to health care providers, patients, and the public.  Efforts include:

Identification of health problem
Epidemiologic & basic research to identify  potential risk factors, mechanisms, & influences
Clinical trials to determine efficacy of novel therapies on health outcomes
Translation of research from the bench to the bedside, and back
Dissemination of information through national education programs

The Institute aims to move advances in basic science, achieved at the “bench,” into trial of novel therapies in patients at the “bedside.”  The NIDDK also strives to use knowledge gained during such trials to fuel future laboratory studies.

## Slide 32

**Notes:**
I hope that these few examples of NIDDK-funded research convey the vigor and progress of our many research efforts. While it is not possible to list every initiative or program the Institute supports, I believe that the integrated and complementary research and education programs I have outlined illustrate how the Institute, and the NIH, seek to address the serious public health burdens facing the U.S. today.

Griffin P. Rodgers, M.D., M.A.C.P.
Acting Director, National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Department of Health and Human Services