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Medical Management of obesity Perinatal ANGELS Conference Feb 17, 2005. Philip A. Kern. Obesity: excess body fat. Why do we need fat anyway? Energy storage Prevention of starvation Energy buffer during prolonged illness. Evolutionary Perspective.
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Medical Management of obesity Perinatal ANGELS Conference Feb 17, 2005 Philip A. Kern
Obesity: excess body fat • Why do we need fat anyway? • Energy storage • Prevention of starvation • Energy buffer during prolonged illness
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
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
Do You Know Your Own BMI? Weight (lbs) 260 270 280 290 300 190 200 210 220 230 240 250 120 130 140 150 160 170 180 5'0" 5'2" 5'4" 5'6" Height 5'8" 5'10" 6'0" 6'2" 6'4"
Obesity Trends* Among U.S. AdultsBRFSS, 1991-2002 1991 1995 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman) 2002 No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Stroke (hypertension) Respiratory disease (sleep apnea) Heart disease (lipids, diabetes, hypertension) Hormonal abnormalities Diabetes Gallbladder disease Cancer (uterus, breast, prostate, colon) Osteoarthritis Hyperuricemia, Gout Consequences of Obesity 1. National Institutes of Health. Obes Res. 1998;6(suppl 2):51S–209S. 2. World Health Organization. Geneva: WHO; 1998.
Type 2 diabetes Cholelithiasis Hypertension Coronary heart disease 6 6 5 5 3 3 2 2 1 1 0 0 27 27 22 22 23 23 29 29 30 30 <21 <21 24 24 25 25 26 26 28 28 (kg/m2) (kg/m2) Relation Between BMI and Comorbidities Women Men 4 4 Relative Risk Body Mass Index Body Mass Index Willett WC, et al. N Engl J Med. 1999;341:427–434.
Etiology of Obesity Energy Expenditure Sedentary lifestyle Energy Intake High fat, high-calorie diet GeneticPredisposition
Do all obese subjects develop diabetes or ectopic fat? Glu 82, chol 150, bad knees Glu 210, chol 275, CAD
The Diabetes Prevention ProgramA Randomized Clinical Trial to Prevent Type 2 Diabetes in Persons at High RiskThe DPP Research GroupNEJM 346:393-403, 2002
DPP Primary Goal • To prevent or delay the development of type 2 diabetes in persons with impaired glucose tolerance (IGT)
Eligibility Criteria • 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/m2 • All ethnic groups: goal of up to 50% from high risk populations
Study Interventions Eligible participants Randomized Standard lifestyle recommendations Intensive Metformin Placebo Lifestyle (n = 1079) (n = 1073) (n = 1082)
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
DPP: Mean Change in Leisure Physical Activity Lifestyle Metformin Placebo The DPP Research Group, NEJM 346:393-403, 2002
DPP: Mean Weight Change Placebo Metformin Lifestyle The DPP Research Group, NEJM 346:393-403, 2002
DPP: Incidence of Diabetes Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Placebo) Lifestyle (n=1079, p<0.001 vs. Metformin , p<0.001 vs. Placebo) Risk reduction 31% by metformin 58% by lifestyle The DPP Research Group, NEJM 346:393-403, 2002
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
Treatments for Obesity • Lifestyle modification • Pharmacotherapy • Surgery Safer DJ. South Med J. 1991;84:1470–1474.
Treatment of ObesityLifestyle 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
The importance of exercise for weight maintenance Exercise No exercise
Obese mouse and littermate The future of obesity drugs • 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
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
UAMS Weight Control ProgramPhase 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