The Growing Epidemic of Diabetes

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The Ad Hoc Group for Medical Research Luncheon Briefing for Senate and House Staff The Growing Epidemic of Diabetes and What the NIH Is Doing About It Griffin. Rodgers, M.D., M.A.C.. Director National Institute of Diabetes and Digestive and Kidney Diseases September 15, 2011

NIDDK s Integrated Research rograms Obesity Type 2 Diabetes Chronic Kidney Disease Approx. 2/3 of U.S. adults overweight Approx. 25.8 million U.S. cases (8.3% of Approx. 23 million U.S. or obese population) cases of CKD Approx. 1/3 of U.S. rojected to ~50 Major causes: adults obese million by 2050 diabetes, Increasing in the Increasing in the hypertension young young ESRD annual Annual cost: $147B Annual cost: $174B cost: $27B

Obesity Fuels Multiple Medical roblems ulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome ancreatitis Stroke Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Gall bladder disease Cancer breast, uterus, cervix, prostate, kidney, colon, esophagus, pancreas, liver Idiopathic intracranial hypertension Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Osteoarthritis i Sex: Age: Wiht Weight: Height: BMI: Female Skin 36 40 120 250 lbs. Gout 5 5 5 6 20.0 40.3 hlebitis venous stasis Images courtesy of Dr. Steven B. Heymsfield

Age adjusted ercentage of Obese and Diabetic U.S. Adults Obesity 1994 2000 2009 Diabetes (diagnosed) 10 14% 15 19% 20 24% 25 29% 30% <4.5% 4.5 5.9% 6.0 7.4% 7.5 8.9% 9.0% Source: Centers for Disease Control and revention

Research rogress at All Stages of Type 1 Diabetes T1DGC revent onset of Stop autoimmune autoimmunity attack 100 Beta Cell Ma ass (%) 10 0 Risk, triggers Autoantibody + Dysglycemia reserve Beta cells Recentonset Restore β cell function Improve glucose Artificial revent, arrest, control reverse complications ancreas Established Complications Time

The Diabetes revention rogram: Collaborative and Transformative ercent Reduction in Diabetes Incidence Compared to lacebo 0 Metformin 30 60 Intensive Lifestyle Intervention Diabetes revention rogram (D) 3,234 individuals at risk for type 2 diabetes Lifestyle modification lowered risk by 58% (modest weight loss, from exercise and reduced fat and caloric intake) Metformin medication lowered risk by 31%

Strategic lanning for Research Building on Advances, Seizing Opportunities

Common Genetics, but Environmental Differences ima Indian Family in Mexico ima Indian Family in the US U.S. Images from Scientific American 275: 88, Aug. 1996

Lifestyle Interventions in Overweight and Obese regnant Women A New NIH research initiative To test lifestyle interventions for overweight or obese pregnant women, in order to improve weight and metabolic outcomes in both the pregnant womenand their offspring

Genes and Environment Initiative http://genesandenvironment.nih.gov/ p //g g / EXOSURE BIOLOGY ROGRAM Develop technology and biomarkers Nutrition hysical Activity Environmental Exposures GENETICS ROGRAM Identify genetic variants GXE GWA Studies Data Analysis Replication Sequencing Database Function Translation

In a Nutshell dbw dt =?

Model Equations DNL dg C CI DNL GNG GNGF G3 CarbOx dt df F 3M FFAFI M TG d DNL KU excr 1 k KTG FatOx dt d I GNG rotox dt FFM BM ECF EC LCM BM ECF EC ICW G ICS BM ECF EC ICW ˆ (1 h ) G(1 h ) ICS decf 1 Na N a diet Na ECF ECF init CI 1 CI CI b ECF dt Na d ECF dt Lancet 378: 826 837, 2011 BW BW init BW BW ECF TEE TEF AE RMR RMR E M FFM M G 1 h ECF ECF c B B FFM B g init F F (1 ) DNL (1 )( GNG GNG ) 1 KTG Lancet 378: 826 837, 2011 d df dg N N excr ( ) D F D F F G DG G dt dt dt dt b http://bwsimulator.niddk.nih.gov/ T ˆ FFM d t d g F K 1 EI EIb T, if EI EI 2 EI EIb T, else dm i i dffm i ˆ 1 1 FFM FFM T AE 1 T BW BW TEF CI G G init G G d F init FI K d d DNL I D G C CI ˆ G DG G init G CarbOx GNG GNG G3 f TEE f p C FatOx KetOx ff TEE rotox f TEE D Dˆ I Keys Ib 2 3 ˆ F D D L L F F F diet A

hysical Activity has Become a To Do Item, Rather than a Lifestyle