1. Medical Management of obesity Perinatal ANGELS Conference Feb 17, 2005 Philip A. Kern

2. Obesity: excess body fat Why do we need fat anyway? Energy storage Prevention of starvation Energy buffer during prolonged illness

4. Evolutionary Perspective Starvation and infection has been a threat to human survival Adipose tissue accumulation would represent a survival adaptation Only recently in Western cultures has unlimited food intake, and little need for physical activity been possible

5. Definition of obesity Elevated Body Mass Index (BMI) (Weight (kg)/height (m) 2 ) BMI <25: normal BMI 25-30: overweight BMI >30: obese BMI>35: very obese

6. Do You Know Your Own BMI? 5'4" Height Weight (lbs) 5'2 " 5'0" 5'10" 5'8" 5'6" 6'0" 6'2" 120130150160170180 190200210220230240250 140 260270280290300 6'4"

7. 19911995 2002 Obesity Trends* Among U.S. Adults BRFSS, 1991-2002 No Data <10% 10%–14% 15%–19% 20%–24% ≥25% (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

8. Consequences of Obesity 1. National Institutes of Health. Obes Res. 1998;6(suppl 2):51S – 209S. 2. World Health Organization. Geneva: WHO; 1998.

9. Willett WC, et al. N Engl J Med. 1999;341:427–434. Relation Between BMI and Comorbidities 465 3 2 1 0 Body Mass Index Relative Risk Women Men Body Mass Index 65 3 2 1 0 4 Type 2 diabetes CholelithiasisHypertension Coronary heart disease <21 2223 242526 27 28 2930 <21 2223 242526 27 28 2930 (kg/m 2 )

12. Childhood obesity in Arkansas 2004

14. EnergyIntake EnergyExpenditure High fat, high-calorie diet Genetic Predisposition Sedentarylifestyle Etiology of Obesity

15. Do all obese subjects develop diabetes or ectopic fat? Glu 82, chol 150, bad kneesGlu 210, chol 275, CAD

16. The Diabetes Prevention Program A Randomized Clinical Trial to Prevent Type 2 Diabetes in Persons at High Risk The DPP Research Group NEJM 346:393-403, 2002

17.  To prevent or delay the development of type 2 diabetes in persons with impaired glucose tolerance (IGT) DPP Primary Goal

18. Age > 25 years Plasma glucose –2 hour glucose 140-199 mg/dl and –Fasting glucose 95-125 mg/dl (5.3- <7.0 mmol/L) Body mass index > 24 kg/m 2 All ethnic groups: goal of up to 50% from high risk populations Eligibility Criteria

19. Study Interventions Eligible participants Randomized Standard lifestyle recommendations Intensive Metformin Placebo Lifestyle (n = 1079) (n = 1073) (n = 1082)

20. Lifestyle Intervention Structure 16 session core curriculum (over 24 weeks) Long-term maintenance program Supervised by a case manager Access to lifestyle support staff –Dietitian –Behavior counselor –Exercise specialist

21. DPP: Mean Change in Leisure Physical Activity Placebo Metformin Lifestyle The DPP Research Group, NEJM 346:393-403, 2002

22. Placebo Metformin Lifestyle DPP: Mean Weight Change The DPP Research Group, NEJM 346:393-403, 2002

23. Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Placebo) Lifestyle (n=1079, p<0.001 vs. Metformin, p<0.001 vs. Placebo) DPP: Incidence of Diabetes Risk reduction 31% by metformin 58% by lifestyle The DPP Research Group, NEJM 346:393-403, 2002

24. Consistency of Treatment Effects Lifestyle intervention was beneficial regardless of ethnicity, age, BMI, or sex The efficacy of lifestyle relative to metformin was greater in older persons and in those with lower BMI The efficacy of metformin relative to placebo was greater in those with higher baseline fasting glucose and BMI

25. Treatments for Obesity –Lifestyle modification –Pharmacotherapy –Surgery Safer DJ. South Med J. 1991;84:1470–1474.

26. Treatment of Obesity Lifestyle modification Nutrition education; where are the fats, increased use of raw foods Behavior modification; self-monitoring, impulse control, reinforcement, environmental control, social support, attitude changes, etc. Exercise Fixed food choices; use of food supplements

27. The importance of exercise for weight maintenance Exercise No exercise

29. The future of obesity drugs Obese mouse and littermate At present, drugs for obesity are not nearly as effective as our drugs for hypertension, cholesterol, even HIV The discovery of leptin has revolutionized research into central appetite control

30. UAMS Weight Control Program Weekly classes Periodic medical monitoring (MD visit, blood) Use of dietary supplement 5 supplements (800 cal/day) 5 supplements plus unlimited non-caloric veggies (~900 cal/day) 4 supplements plus one meal (~1100 cal/day) 15 week core curriculum Typical 15-week weight loss: 20-50 lbs Weight stabilization and long-term weight maintenance

31. UAMS Weight Control Program Phase II: Weight Stabilization Weekly classes Periodic medical monitoring (MD visit, blood) Gradual re-introduction of food, and decrease in the use of dietary supplement 4 weeks Calories: gradually increase to weight maintenance level

33. “The modern threat to survival”