Obesity: A Metabolic Perspective

Obesity Trends* Among U.S. Adults BRFSS, 1985 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14%

Obesity Trends* Among U.S. Adults BRFSS, 1986 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14%

Obesity Trends* Among U.S. Adults BRFSS, 1987 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14%

Obesity Trends* Among U.S. Adults BRFSS, 1988 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14%

Obesity Trends* Among U.S. Adults BRFSS, 1989 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14%

Obesity Trends* Among U.S. Adults BRFSS, 1990 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14%

Obesity Trends* Among U.S. Adults BRFSS, 1991 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1992 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1993 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1994 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1995 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1996 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1997 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults BRFSS, 1998 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults BRFSS, 1999 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults BRFSS, 2000 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults BRFSS, 2001 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) Obesity Trends* Among U.S. Adults BRFSS, 2002 No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. Adults BRFSS, 2003 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. Adults BRFSS, 2004 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. Adults BRFSS, 2005 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity as a Risk Factor for CAD The Importance of Abdominal Fat Gynoid Obesity Android Obesity Sharma 2002

Android Obesity Obesity and Metabolic Risk Abdominal vs. Peripheral Obesity Small Insulin-Sensitive Adipocytes Gynoid Obesity Large Insulin-Resistant Adipocytes Sharma 2002

Obesity and Cardiovascular RiskHypertension Left ventricular hypertrophy Congestive heart failure Prothrombosis Fibrinogen  PAI-1  Insulin resistance Glucose intolerance Hyperglycaemia Type 2 diabetes Endothelial dysfunction Dyslipidaemia Total-C  LDL-C  Triglycerides  Apo-B  HDL-C  Renal Hyperfiltration Albuminuria Inflammatory Response  Visceral Obesity

“Corpulence is not only a disease itself, but the harbinger of others” Hippocrates

10 March 2004

Common Morbidities linked with Obesity

Consequences

Portugal 1.5% Luxembourg 3.3% Prevalence of Obesity in Year Old Europeans (BMI>30) Ireland 8.0% Belgium 4.1% Spain 1.4% Italy 1.0% Greece 11.0% Austria 5.2% Denmark 2.5% Finland 1.2% Sweden 2.0% Netherlands 4.8% UK 3.5% Germany 3.0% France 1.8% Martinez JA, Public Health Nutr 1999;2(1A):125-33

Cases of Type 2 Diabetes/100,000 ADA - Consensus statement reported in Diabetes Care 2000;22(12):381 Incidence of Type 2 Diabetes in Junior High School Japanese Children

“Most of these persons will not stay in treatment for obesity. Of those who stay in treatment most will not lose weight. Of those who do lose weight, most will regain it”. Stunkard 1972

Treating obesity: how and why

Treatment efficacy? There is no community intervention programme worldwide that has successfully allowed long term weight loss (maintenance) Overall failure rate after 4 years is 96% Minnesota ‘Pound of Prevention’ study indicated the mean weight gain prevented was <1kg

Treatment efficacy? Long term studies indicate only a small proportion of people lose and then maintain lost weight Predictors of success: –Continuous consumption of low-energy, low-fat food, <25% –Food diary –Breakfast

Management Goals Moderate weight loss of 5 to 10 kg will have a major effect on obesity co-morbidities - impaired glucose metabolism hypertension dyslipidaemia sleep apnea polycystic ovary syndrome The weight loss needs to be sustained

Treatment benefits? Diabetes Prevention Program (USA) N=3234 (67% female); IGT 50.6 years, Weight 94.8kg BMI 34 kg/m years Lifestyle intervention Metformin Placebo

Treatment benefits? Diabetes Prevention Program Research Group 346 (6): 393, Figure 2 February 7, 2002

Treatment benefits? Diabetes Prevention Program Research Group 346 (6): 393, Figure 1 February 7, 2002 Goal weight loss: 7% (6.6kg)

Treatment benefits? Diabetes Care 28: , 2005

Treatment benefits? Diabetes Care 28: , 2005

Obesity management strategies Diet Physical activity Pharmacotherapy Surgery

Obesity management strategies Diet –Best achieved by a combination of hypocaloric/low fat diet –Aim to reduce intake by kJ/day –32000 kJ = 1kg –0.5kg / week

Obesity management strategies Diet Physical activity –30 mins 3 times a week is not sufficient to allow weight loss or to maintain lost weight –Current recommendations: mins moderate intensity exercise daily

Obesity management strategies Diet Physical activity Pharmacotherapy –Duromine –Fluoxetine –Sibutramine –Xenical –Optifast

Sibutramine: mechanism of action Serotonin (5-HT) and noradrenaline reuptake inhibitor. Dual mode of action: –reduces food intake by enhancing satiety –increases energy expenditure by enhancing resting metabolic rate Side effects –Hypertension, tachycardia –Serotonin syndrome (SSRI’s, anti-psychotics) McNeely and Goa. Drugs 1998.

Xenical : mechanism of action Inhibits gastrointestinal lipases which are required for the systemic absorption of dietary fat Prevents the absorption of 30% of dietary fat Safe with minimal systemic absorption and no accumulation Significant GI side effects

Xenical (n=8) Sibutramine (n=8)  Kg -1kg-4kg  HbA1c -0.7%0% SCGH prescriptions for Xenical and Sibutramine 6 months therapy 10% lose >10 kg at 6-12 months

Management of Obesity: Objectives Prevention of weight gain Encourage sustainable weight loss over longer term Promotion of weight loss 0.5 to 1.0kg per month is reasonable Up to a 10% reduction in body weight over a 12 month period Improvement of co-morbidities Attainable with a weight loss as low as 5% Encouragement of active lifestyle Broaden concepts of activity Improvement in quality of life Enhance feelings of “well-being” * NHLBI Clinical Guidelines 1998