The Epidemic: The Biology of Affluence Norman G. Hord, PhD, MPH, RD Department of Food Science and Human Nutrition
Dec 18, 2015
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.