The
Epidemic:
The Biology of Affluence
Norman G. Hord, PhD, MPH, RD
Department of Food Science and Human Nutrition
Outline
I.
The Obesity Epidemic: Definition and Trends
II.
Obesity and Co-morbidities
III.
Metabolic Abnormalities Associated with Obesity
IV.
Possible Solutions
V.
Summary
NHLBI Guidelines
http://www.nhlbi.nih.gov/nhlbi/cardio/obes/prof/guidelns/ob_home.htm
American Dietetic Association Position Paper on Weight Management
http://www.eatright.org/adap0197.html
Experts in Obesity
• George Bray, M.D.
• Thomas Namey, M.D.
• Micheal Zemel, Ph.D.
• Sachiko St. Jeor, Ph.D.
• George Blackburn,
M.D., Ph.D.
• Kelly Brownell, Ph.D.
Obesity is a complex multifactorial chronic disease that
develops from an interaction of genotype and the
environment. Our understanding of how and why obesity
develops is incomplete, but involves the integration of social,
behavioral, cultural, physiological, metabolic and genetic
factors.
Clinical Guidelines on the Identification, Evaluation, and
Treatment of Overweight and Obesity in Adults, The Evidence
Report. National Institutes of Health, National Heart, Lung,
and Blood Institute, June 1998.
Assessment of Obesity
Body Mass Index
Waist Circumference
Weight (kg) / Height (m)2
Weight (lbs) X 703
Height Squared (in 2)
Underweight
Normal
Overweight
Obese
Morbid Obesity
Good Estimate of
Central Adiposity
Men:
Women:
< 18
18-24
25-29
> 30
> 40
40”
35”
Weight Gain since age 18
Level of Fitness
Bjorntorp P. Obesity. Lancet 350: 423-426, 1997
The Obesity Epidemic
• U.S.: 20% of men & 25% of women are obese.
• 97 million Americans are overweight or obese.
(59.4% of men and 51% of women)
• >10% of 4-5 year old children are obese.
– ~2-fold increase over preceding decade
These increases have occurred despite successes in reducing
dietary fat as % of kcal.
Source: NCHS, National Health and Nutrition Examination Survey,1997
Guess BMI?
~30% of urban Indians are obese.
Experts blame high-fat diets and
lack of exercise.
© CNN
© CNN
http://cnn.com/WORLD/asiapcf/9810/25/india.obesity/index.html
Kuczmarski et al. National Health and Nutrition Examination Surveys,
MMWR; 43: 818-821,1994.
Prevalence of Obesity in the U.S.
Ethnicity
Males (%)
Females (%)
African American
26
44
Mexican American
31
42
Native American
34
40
Puerto Rican
26
40
White
31
35
Source: NHANES III, National Center for Health Statistics,
Center for Disease Control, Public Health Service, USDHHS.
Obesity as a Disease
• Causes ~300,000 deaths per year in U.S.
– 2nd cause of preventable mortality to smoking
in US (~400,000/ year).
•
NHLBI Expert Panel ascribes the causes of obesity to
60% environmental influences/ 40% genetic influences.
• Obesity is caused by the superimposition of specific
environmental conditions on a susceptible genotype.
Costs of Obesity and its Co-morbidities
• $51 billion (5.7% of total US health care
expenditures) in direct costs.
• $33 billion spent on weight loss aids
• Indirect costs: 39 million lost work days
239 million restricted activity days
• Total: $300 million excess cost/ million adults
Wolf and Colditz. Obesity Research 6: 97-106, 1998
Consequences of Modest Weight
Gain
10% increase in weight results in:
Fasting Blood Glucose of 2-3 mg/dL
Systolic Blood Pressure of 6-7 mm Hg
Conditions Associated With Obesity
(Relative Risk)
Diabetes Mellitus
(Type II)
(RR>>3)
Stroke
(RR= 2-3)
Gall Bladder Disease
(RR>>3)
Obesity
Coronary Heart Disease Gout
(RR= 2-3)
(RR=2-3)
Sleep Apnea
(RR>>3)
Hypertension
(RR>>3)
Osteoarthritis
(RR=2-3)
Upper Body Fat Distribution Increases
Metabolic Complications
Central or Visceral Adiposity
vs.
Excess central or abdominal fat
is an independent predictor of
disease risk.
Visceral fat is more metabolically
active.
Highly susceptible to Syndrome X.
Subcutaneous Adiposity
Minimal risk associated
with lower body obesity.
Lipoprotein Lipase
Releases TGs from
Visceral Adipose
Hyperglycemia
Hypertriglyceridemia
Insulin Resistance
VLDL cholesterol
HDL cholesterol
Insulin Resistance
Hyperinsulinemia
HDL Cholesterol
SYNDROME X
VLDL
Cholesterol
Hypertriglyceridemia
Hypertension
Glucose
Intolerance
DEADLY QUARTET
Android Obesity
Zemel M. 1998. National Conference on Obesity and Co-morbidities,
Ft. Myers, FL.
Common Hormonal Abnormalities in Obesity
• Increased cortisol production
• Insulin resistance
• Decreased sex hormone binding globulin
(women)
• Decreased progesterone levels in women
• Decreased testosterone levels in men
• Decreased growth hormone production
Lipoprotein Lipase
Leptin
PAI-1
IL-6
Adipsin
(Complement D)
Lactate
Serum Free Fatty Acids
Angiotensinogen
Behavioral Treatment
Pharmacotherapy
Diet and Exercise
Benefits of Modest Weight Loss
• Normalizes high blood pressure
• Blood levels
•
•
•
•
•
LDL cholesterol
Insulin
Glycated hemoglobin (HbA1C)
Blood glucose
Uric acid
•
HDL Cholesterol
• Improved Quality of Life
Realistic Treatment Goals
1.
5-10% Weight Loss
2.
Focus on Health, Fitness, and Energy Level
3.
Positive Mood and Appearance
4.
Functional and Recreational Activities
Key Elements of Treatment Success
1.
Adherence to treatment for at least 5 years.
2.
Food and physical activity diaries.
3.
Gradual increase in physical activity.
4.
Gradual decrease in dietary fat.
5.
No feelings of food deprivation.
6.
Social support groups.
Possible Solutions
• Surgery:
Gastric Stapling
Gastric Bypass
• Pharmaceuticals
• Diet/Exercise
• Divine Intervention
BMI > 40
Drugs that decrease food intake
•
•
Leptin
Peptides
- Neuropeptide Y (NPY)
- Cholecystokinin (CCK)
Nutrient partitioning drugs
•
Orlistat (Xenical)
Drugs to increase energy expenditure
•
UCP2, ß3 Adrenoreceptor gene
Leptin
•
Protein product of the ob gene secreted by adipose tissue.
•
Binds receptors in the hypothalamus and inhibits NPY,
a potent stimulator of binge eating.
•
Homozygous recessive ob mice are leptin deficient and
develop severe obesity.
•
Leptin treatment causes decreased food intake and
weight loss in ob/ob mice.
Leptin in Humans
•
Human homologue for the ob gene has been identified
on chromosome 7.
* Leptin levels and BMI are highly correlated (r=0.86).
* Defects in the ob gene in humans are rare.
* Obese individuals may be insensitive to leptin.
* Premorbidly low leptin levels may predispose
some individuals to weight gain.
First GI Lipase
Inhibitor
Acts locally in
GI Tract
Orlistat
(Xenical®)
Blocks ~30% of
Dietary Fat
Absorption
No CNS Effect
No Appetite Effect
Nutrient Partitioning of Orlistat
Absorption
•Minimal (<1%)
•No accumulation in blood
or tissue
Metabolism
of Orlistat
•GI epithelium
•2 main metabolites are
“inert”.
Excretion
•Fecal excretion is
major pathway
•
Produces clinically meaningful, sustained
weight loss
•
Diminished weight regain
•
Maintained effectiveness over 2 years
•
Severity of risk factors more effectively than
diet alone:
-improved lipid profiles
-decreases blood pressure
-improves fasting insulin levels
-improves glycemic control in type II DM.
FDA-Approved Anorexiant Drugs
Depress food intake by altering neurotransmitter release,
reuptake or acting as receptor agonists.
Fenfluramine/Phentermine (Fen/Phen)
Valvular heart disease in 8-32% of patients caused FDA to
withdraw approval of this type of treatment in 1997.
Sibutramine (Meridia®)
•
Acts by inhibiting serotonin and norepinephrine
reuptake.
•
Enhances satiety.
•
>20 clinical trials have proven efficacy and safety.
•
No cardiac, lung, or neurotoxicities noted.
http://www.naafa.org
….and he set himself a task of sawing wood
for a half an hour per day and was nearly cured.
Dr. Heberden
British physician (1802)
Photo by Joel Steen
Obesity is a growing problem in developed and developing
nations.
Drug treatments have so far been limited in efficacy; some
have had serious side effects.
Maintenance of energy balance is complex and affected by
hormonal, genetic, psychosocial, and environmental factors.
Heterogeneous genetic disorders are associated with obesity,
thwarting efforts to develop “magic bullets” against this disease.
Hirsch, J. 1998. Magic bullet for obesity. BMJ 317: 1136-1138.