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)
120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300
5'0"
5'2"
5'4"
Height
5'6"
5'8"
5'10"
6'0"
6'2"
6'4"
Obesity Trends* Among U.S. Adults
BRFSS, 1991-2002
(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)
1991
1995
2002
No Data
<10%
10%–14%
15%–19%
20%–24%
≥25%
Consequences of Obesity
Stroke (hypertension)
Respiratory disease (sleep apnea)
Heart disease (lipids,
diabetes, hypertension)
Hormonal abnormalities
Gallbladder disease
Diabetes
Osteoarthritis
Cancer (uterus, breast,
prostate, colon)
Hyperuricemia, Gout
1. National Institutes of Health. Obes Res. 1998;6(suppl 2):51S–209S.
2. World Health Organization. Geneva: WHO; 1998.
Relation Between BMI and
Comorbidities
Women
Men
6
6
5
5
4
4
3
3
2
2
1
1
0
<21
22
23
Type 2 diabetes
Cholelithiasis
Hypertension
Coronary heart
disease
24
25
26
27
28
29
30
Body Mass
Index
(kg/m2)
Willett WC, et al. N Engl J Med. 1999;341:427–434.
0
<21 22
23
24
25
26
27
Body Mass
Index
(kg/m2)
28
29
30
Childhood obesity in Arkansas 2004
Etiology of Obesity
Energy
Expenditure
Sedentary
lifestyle
Energy
Intake
High fat,
high-calorie diet
Genetic
Predisposition
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 Group
NEJM 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
Lifestyle
(n = 1079)
Metformin
(n = 1073)
Placebo
(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
MET-hours/week
8
Lifestyle
6
4
Metformin
Placebo
2
0
0
1
2
Years from Randomization
The DPP Research Group, NEJM 346:393-403, 2002
3
4
Weight Change (kg)
DPP: Mean Weight Change
0
Placebo
Metformin
-2
Lifestyle
-4
-6
-8
0
1
2
Years from Randomization
The DPP Research Group, NEJM 346:393-403, 2002
3
4
developing diabetes
DPP:Percent
Incidence
of Diabetes
All
Placebo (n=1082)
Metformin (n=1073, p<0.001 vs. Placebo)
Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )
Lifestyle
p<0.001vs.vs.
Metformin ,
Metformin(n=1079,
(n=1073, p<0.001
Plac)
Placebo (n=1082) p<0.001 vs. Placebo)
Cumulative incidence (%)
40
30
participants
Risk reduction
31% by metformin
58% by lifestyle
20
10
0
0
1
2
Years from randomization
The DPP Research Group, NEJM 346:393-403, 2002
3
4
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 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
The importance of exercise for weight maintenance
Exercise
No exercise
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
Obese mouse
and littermate
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”