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

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:

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

Organizational Structure of NIDDK’s Three Extramural Scientific Divisions NIDDK KUH Division of Kidney, Urologic, and HematologicDiseases DDN Division of Digestive Diseases andNutrition DEM Division of Diabetes, Endocrinology,and Metabolic Diseases

A Paradigm of NIDDK’s Integrated Research Programs Obesity Type 2 Diabetes KidneyDisease

Overweight and Obesity 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 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 For Adults For Children and Adolescents

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 steatosissteatohepatitiscirrhosis 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

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

PercentPercent 6-11 years old years old Trends in U.S. Child and Adolescent Overweight

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

Obesity Type 2 Diabetes KidneyDisease A Paradigm of NIDDK’s Integrated Research Programs

Two Major Forms of Diabetes 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 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 Type 1 Type 2

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

Diabetes: Burden of Disease 20.8 million Americans (7 percent of the U.S. population) have diabetes 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)

People (millions) Year Diagnosed Diabetes in the U.S. Diagnosed ( ) and Projected Diagnosed ( ) Cases Diagnosed cases Projected diagnosed cases

Results from the Diabetes Prevention Program Substantial Reduction in Diabetes in All Race-Ethnic Groups LifestyleMetformin Placebo/Standard care Cases per 100 person-years All participants CaucasianAfrican American HispanicAmerican Indian Asian

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

Obesity Type 2 Diabetes KidneyDisease A Paradigm of NIDDK’s Integrated Research Programs

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

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

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

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

Incident Diabetic End-stage Renal Disease in the U.S. Age 20 to 29 Years Year Per million population Caucasian African American

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

Eye Disease: Intensive Diabetes Treatment Reduces Risk Study Years Cumulative Percent Conventional Cumulative Incidence of > 3-Step Change p = Intensive

Cumulative Incidence of Nonfatal Myocardial Infarction, Stroke, or Death from Cardiovascular Disease Years Since Entry into DCCT/EDIC Study Conventional Intensive Heart Disease: Intensive Diabetes Treatment Reduces Risk

NIH and NIDDK Strategic Research Plans

Strategic Plan for NIH Obesity Research 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 Developed by the NIH Obesity Research Task Force with critical input from external scientists and the public 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.

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

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

Examples of NIH and NIDDK Education and Outreach Programs

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. 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.

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

National Kidney Disease Education Program NKDEP 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.

Aerial View of NIH campus in Bethesda, MD