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

1. Research Highlights from the National Institute of Diabetes and Digestive and Kidney Diseases Griffin P. Rodgers, M.D., M.A.C.P. Acting Director

2. National Institute of Diabetes and Digestive and Kidney Diseases • Diabetes, Endocrinology, and Metabolic Diseases; • Digestive Diseases and Nutrition; and • Kidney, Urologic, and Hematologic Diseases. The NIDDK conducts and supports basic and applied research and provides leadership for a national program in:

3. NIDDK’s Research and Dissemination Spectrum “Bench to Bedside and Beyond”

4. Organizational Structure of NIDDK’s Three Extramural Scientific Divisions NIDDK DDN DEM KUH Division of Digestive Diseases and Nutrition Division of Kidney, Urologic, and Hematologic Diseases Division of Diabetes, Endocrinology, and Metabolic Diseases

5. A Paradigm of NIDDK’s Integrated Research Programs Kidney Disease Type 2 Diabetes Obesity

6. Overweight and Obesity For Adults • BMI below 18.5 – Underweight • BMI between 18.5 and 24.9 – Healthy weight • BMI between 25 and 29.9 – Overweight • BMI 30 and above – Obese For Children and Adolescents • BMI below 5th percentile – Underweight • BMI between 5th and less than 85th – Healthy weight • BMI between 85th and less than 95th – At Risk of Overweight • BMI 95th percentile and above – Overweight

7. Health Complications of Obesity Stroke Idiopathic intracranial hypertension Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Cataracts Coronary heart disease Pancreatitis Diabetes Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Dyslipidemia Hypertension Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Gall bladder disease Cancer breast, uterus, cervix, prostate, kidney colon, esophagus, pancreas, liver Osteoarthritis Phlebitis venous stasis Skin Gout

8. 1991 Obesity Trends Among U.S. Adults 2004 No Data <10% 10-14% 15-19% 20-24% ≥25%

9. Trends in U.S. Child and Adolescent Overweight 20 20 15 15 6-11 years old Percent Percent 10 10 12-19 years old 5 5 0 0 1971-1974 1976-1980 1988-1994 1963-1967 1999-2000 2001-2002 2003-2004

10. Obesity: Gene/Environment Interactions Current environment Adipocity phenotype (e.g., body mass index) Past environment Genetic susceptibility

11. A Paradigm of NIDDK’s Integrated Research Programs Kidney Disease Type 2 Diabetes Obesity

12. Two Major Forms of Diabetes Type 1 • Usually diagnosed in childhood, adolescence, or young adulthood • Body’s immune defense system mistakenly destroys insulin-producing cells in the pancreas (autoimmunity) • Results in lack of insulin to control blood sugar levels; insulin therapy lifesaving but not a cure Type 2 • Historically diagnosed in adults; now in children and adolescents • Body has reduced sensitivity to insulin • Therapy increases insulin release/sensitivity; some insulin administration may be required • Obesity is a serious risk factor • Can be prevented or delayed by diet and exercise as shown in NIH clinical trials

13. 1994 2004 Estimates of Diagnosed Diabetes Among Adults in the U.S. No Data <4% 4-4.9% 5-5.9% ≥6%

14. Diabetes: Burden of Disease • 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)

15. Diagnosed Diabetes in the U.S. Diagnosed (1960-2004) and Projected Diagnosed (2005-2050) Cases 50 40 30 Diagnosed cases People (millions) Projected diagnosed cases 20 10 0 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 Year

16. 15 12 9 Cases per 100 person-years 6 3 0 All participants Caucasian African Hispanic American Asian American Indian Metformin Placebo/Standard care Lifestyle Results from the Diabetes Prevention Program Substantial Reduction in Diabetesin All Race-Ethnic Groups

17. Complications Common to Both Type 1 and Type 2 Diabetes Acute complications Stroke • Dangerously high or low blood glucose → coma, death Blindness Heart Disease Chronic complications Kidney Disease • Affect all major organs • Develop over time/ exposure to high blood glucose • Tight control of blood glucose can prevent or delay Atherosclerosis Foot Ulcers and Amputations

18. A Paradigm of NIDDK’s Integrated Research Programs Kidney Disease Type 2 Diabetes Obesity

19. End-stage Renal Disease in the U.S. Number of Patients per Million Population 1993 2003

20. End-stage Renal Disease in the U.S.All Values are for Calendar Year 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

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

22. Progress in Combating the U.S. ESRD Epidemic • After 20 years of annual increases from 5 to 10 percent, rates for new cases of kidney failure have stabilized • Better disease prevention methods appear to be responsible • Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers • Better glycemic control • Better blood pressure control • NIH research has established the value of these interventions But, progress has not yet been realized across all U.S. populations

23. Incident Diabetic End-stage Renal Disease in the U.S.Age 20 to 29 Years 35 30 Caucasian African American 25 20 Per million population 15 10 5 0 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

24. More Insights into Preventing Complications of Diabetes • Microvascular damage – retinopathy • Macrovascular damage – CVD • Preventing complications by preventing diabetes - DPP

25. Conventional p = 0.001 Intensive Eye Disease: Intensive Diabetes Treatment Reduces Risk 100 Cumulative Incidence of > 3-Step Change 75 Cumulative Percent 50 25 0 0 1 2 3 4 5 6 7 8 9 Study Years

26. Conventional Intensive Heart Disease: Intensive Diabetes Treatment Reduces Risk 0.06 0.04 Cumulative Incidence of Nonfatal Myocardial Infarction, Stroke, or Death from Cardiovascular Disease 0.02 0.00 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Years Since Entry into DCCT/EDIC Study

27. NIH and NIDDK Strategic Research Plans

28. Strategic Plan for NIH Obesity Research Developed by the NIH Obesity Research Task Force with critical input from external scientists and the public • Research Toward Preventing and Treating Obesity Through Behavioral and Environmental Approaches to Modify Lifestyle, with an Emphasis on Childhood Obesity • Research Toward Preventing and Treating Obesity Through Pharmacologic, Surgical, or Other Medical Approaches • Research Toward Understanding the Relationship Between Obesity and Its Associated Health Conditions • Cross-cutting Topics – Technology, Multidisciplinary/Interdisciplinary Research Teams, Translational Research, Training, Education/Outreach Although listed separately, the first two themes are interdependent. We seek to create an interdisciplinary approach in which lifestyle interventions are informed by an understanding of the basic biological and genetic factors and vice versa.

29. Conquering Diabetes: A Scientific Progress Report on The Diabetes Research Working Group’s Strategic Plan Highlights of Program Efforts, Research Advances and Opportunities related to: • Genetics • Autoimmunity and the Beta Cell • Cell Signaling and Cell Regulation • Obesity • Clinical Research and Clinical Trials of Critical Importance

30. Progress and Priorities: Renal Disease Research Plan • Important scientific resources needed to reach research goals include: • Conducting More Epidemiological Studies • Creating Centers and Cooperatives • Creating New Ways to Study Renal Injury • Focusing More on Genetic Susceptibility • Developing a Renal Genomics Project • Increasing Research on Treatments

31. Examples of NIH and NIDDK Education and Outreach Programs

32. Weight-control Information Network The Weight-control Information Network (WIN) is an information service of the NIDDK. WIN was established in 1994 to provide the general public, health professionals, the media, and Congress with up-to-date, science-based information on obesity, weight control, physical activity, and related nutritional issues. WIN produces, collects, and disseminates materials on obesity, weight control, and nutrition.

33. 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.

34. Components of the National Diabetes Education Program • Control Your Diabetes. For Life. - To promote the importance and benefits of diabetes control • Be Smart About Your Heart. Control the ABCs of Diabetes - Encourages control of blood sugar, blood pressure, and cholesterol • Small Steps. Big Rewards. Prevent type 2 Diabetes - Translate and promote the Diabetes Prevention Program (DPP) clinical trial findings

35. NKDEP National Kidney DiseaseEducation 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.

36. Aerial View of NIH campus in Bethesda, MD