The Epidemic:The Biology of AffluenceNorman 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

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.

NHLBI Guidelineshttp://www.nhlbi.nih.gov/nhlbi/cardio/obes/prof/guidelns/ob_home.htm

American Dietetic Association Position Paper on Weight Managementhttp://www.eatright.org/adap0197.html

Obesity is a complex multifactorial chronic disease thatdevelops from an interaction of genotype and the environment. Our understanding of how and why obesitydevelops 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 EvidenceReport. National Institutes of Health, National Heart, Lung,and Blood Institute, June 1998.

Assessment of ObesityAssessment of Obesity

Weight Gain since age 18

Bjorntorp P. Obesity. Lancet 350: 423-426, 1997

Body Mass Index Waist Circumference

Weight (kg) / Height (m)2 Good Estimate of Central Adiposity

Weight (lbs) X 703 Height Squared (in 2) Men: 40”

Women: 35”

Underweight < 18Normal 18-24Overweight 25-29Obese > 30 Level of Fitness

Morbid Obesity > 40

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 reducingdietary fat as % of kcal.

Source: NCHS, National Health and Nutrition Examination Survey,1997

Guess BMI?

http://cnn.com/WORLD/asiapcf/9810/25/india.obesity/index.html

~30% of urban Indians are obese.

Experts blame high-fat diets and lack of exercise.

© CNN

© CNN

Trends in Age-Adjusted Prevalence of Overweight in U.S.

05

10152025303540

1960-62

1971-74

1976-80

1988-91

Years

MenWomenGoal

Kuczmarski et al. National Health and Nutrition Examination Surveys, MMWR; 43: 818-821,1994.

Prevalence of Obesity in the U.S.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)

Obesity

Diabetes Mellitus Gall Bladder Disease Sleep Apnea (Type II) (RR>>3) (RR>>3) (RR>>3)

Stroke Hypertension(RR= 2-3) (RR>>3)

Coronary Heart Disease Gout Osteoarthritis (RR= 2-3) (RR=2-3) (RR=2-3)

Upper Body Fat Distribution Increases Metabolic Complications

Central or Visceral Adiposity vs. Subcutaneous Adiposity

Excess central or abdominal fat Minimal risk associatedis an independent predictor of with lower body obesity.disease risk.

Visceral fat is more metabolically active.

Highly susceptible to Syndrome X.

Lipoprotein LipaseReleases TGs fromVisceral Adipose

Hypertriglyceridemia

VLDL cholesterol

HDL cholesterol

Insulin Resistance

Hyperglycemia

Insulin Resistance

Hyperinsulinemia HDL Cholesterol

SYNDROME X

VLDL Hypertension Cholesterol GlucoseHypertriglyceridemia 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 IL-6

PAI-1 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 anddevelop 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 identifiedon 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.

Orlistat(Xenical®)

First GI Lipase Acts locally in Inhibitor GI Tract

Blocks ~30% of No CNS EffectDietary Fat No Appetite EffectAbsorption

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 DrugsFDA-Approved Anorexiant Drugs

Depress food intake by altering neurotransmitter release, reuptake or acting as receptor agonists.

Fenfluramine/Phentermine (Fen/Phen)Fenfluramine/Phentermine (Fen/Phen)

Valvular heart disease in 8-32% of patients caused FDA towithdraw approval of this type of treatment in 1997.

Sibutramine (Meridia®)

• Acts by inhibiting serotonin and norepinephrinereuptake.

• 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 woodfor a half an hour per day and was nearly cured.

Dr. HeberdenBritish physician (1802)

Photo by Joel Steen

Obesity is a growing problem in developed and developingnations.

Drug treatments have so far been limited in efficacy; somehave had serious side effects.

Maintenance of energy balance is complex and affected byhormonal, 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.