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?

5'4"5'4"

HeightHeight

Weight (lbs)Weight (lbs)

5'25'2""

5'0"5'0"

5'10"5'10"

5'8"5'8"

5'6"5'6"

6'0"6'0"

6'2"6'2"

120120 130130 150150 160160 170170 180180 190190 200200 210210 220220 230230 240240 250250140140 260260 270270 280280 290290300300

6'4"6'4"

1991 1995

2002

Obesity Trends* Among U.S. AdultsBRFSS, 1991-2002

No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

Consequences of Obesity

Heart disease (lipids, Heart disease (lipids, diabetes, hypertension)diabetes, hypertension)

Respiratory disease (sleep apnea)Respiratory disease (sleep apnea)

Gallbladder diseaseGallbladder disease

Hormonal abnormalitiesHormonal abnormalities

Hyperuricemia, GoutHyperuricemia, Gout

Stroke (hypertension)Stroke (hypertension)

DiabetesDiabetes

OsteoarthritisOsteoarthritisCancer (uterus, breast, Cancer (uterus, breast, prostate, colon)prostate, colon)

1. National Institutes of Health. 1. National Institutes of Health. Obes ResObes Res. 1998;6(suppl 2):51S. 1998;6(suppl 2):51S––209S.209S.2. World Health Organization. Geneva: WHO; 1998.2. World Health Organization. Geneva: WHO; 1998.

Willett WC, et al.Willett WC, et al. N Engl J Med. N Engl J Med. 1999;341:427–434.1999;341:427–434.

Relation Between BMI and Relation Between BMI and ComorbiditiesComorbidities

44

66

55

33

22

11

00

Body Mass Body Mass IndexIndex

Relative Relative RiskRisk

WomenWomen MenMen

Body Mass Body Mass IndexIndex

66

55

33

22

11

00

44

Type 2 diabetesType 2 diabetesCholelithiasisCholelithiasisHypertensionHypertensionCoronary heart Coronary heart diseasedisease

<21<21 2222 2323 2424 2525 2626 2727 2828 2929 3030 <21<21 2222 2323 2424 2525 2626 2727 2828 2929 3030

(kg/m(kg/m22)) (kg/m(kg/m22))

Childhood obesity in Arkansas 2004

Energy Energy IntakeIntake

EnergyEnergyExpenditureExpenditure

High fat, High fat, high-calorie diethigh-calorie diet

GeneticGeneticPredispositionPredisposition

Sedentary Sedentary lifestyle lifestyle

Etiology of Obesity

Do all obese subjects develop diabetes or ectopic fat?

Glu 82, chol 150, bad knees Glu 210, chol 275, CAD

The Diabetes Prevention Program

A Randomized Clinical Trial to Prevent Type 2 Diabetes

in Persons at High Risk

The DPP Research GroupNEJM 346:393-403, 2002

To prevent or delay the

development of type 2 diabetes

in persons with impaired glucose

tolerance (IGT)

DPP Primary Goal

• 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

Eligibility Criteria

Study InterventionsEligible participantsEligible participants

RandomizedRandomized

Standard lifestyle recommendationsStandard lifestyle recommendations

Intensive Metformin PlaceboIntensive Metformin PlaceboLifestyleLifestyle(n = 1079) (n = 1073) (n = 1082)(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

0

2

4

6

8

0 1 2 3 4

Years from Randomization

MET

-hou

rs/w

eek

PlaceboMetformin

Lifestyle

The DPP Research Group, NEJM 346:393-403, 2002

-8

-6

-4

-2

0

0 1 2 3 4

Years from Randomization

Wei

ght C

hang

e (k

g)

Placebo

Metformin

Lifestyle

DPP: Mean Weight Change

The DPP Research Group, NEJM 346:393-403, 2002

0 1 2 3 4

0

10

20

30

40Placebo (n=1082)Metformin (n=1073, p<0.001 vs. Plac)Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )

Percent developing diabetes

All participants

All participants

Years from randomization

Cum

ulat

ive

inci

denc

e (%

)

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 DPP: Incidence of Diabetes

Risk reductionRisk reduction31% by metformin31% by metformin58% by lifestyle58% 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. Safer DJ. South Med J.South Med J. 1991;84:1470–1474. 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

ExerciseNo exercise

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

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 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

“The modern threat to survival”