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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% Obesity Trends* Among U.S. Adults BRFSS, 2002 (*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, 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 Android Obesity Gynoid Obesity Sharma 2002 Obesity and Metabolic Risk Abdominal vs. Peripheral Obesity Large Insulin-Resistant Adipocytes Small Insulin-Sensitive Adipocytes Android Obesity Sharma 2002 Gynoid Obesity Obesity and Cardiovascular Risk Dyslipidaemia Total-C • LDL-C Triglycerides Apo-B • HDL-C Endothelial dysfunction Hypertension Left ventricular hypertrophy Congestive heart failure Visceral Obesity Prothrombosis Fibrinogen PAI-1 Insulin resistance Glucose intolerance Hyperglycaemia Type 2 diabetes Renal Hyperfiltration Albuminuria Inflammatory Response “Corpulence is not only a disease itself, but the harbinger of others” Hippocrates 10 March 2004 Common Morbidities linked with Obesity Stroke Sleep Apnoea Heart disease Gall bladder disease Cardiovascular risk factors Diabetes Osteoarthritis Hormonal abnormalities Hyperuricaemia and gout Cancer Consequences Prevalence of Obesity in 15-24 Year Old Europeans (BMI>30) Ireland 8.0% UK 3.5% Netherlands 4.8% Belgium Germany 3.0% Sweden 2.0% Finland 4.1% 1.2% Luxembourg Denmark Portugal Austria 3.3% 2.5% 1.5% Spain 1.4% 5.2% France 1.8% Martinez JA, Public Health Nutr 1999;2(1A):125-33 Italy 1.0% Greece 11.0% Cases of Type 2 Diabetes/100,000 Incidence of Type 2 Diabetes in Junior High School Japanese Children 14 12 10 8 6 4 1976-80 1981-85 ADA - Consensus statement reported in Diabetes Care 2000;22(12):381 1991-95 “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/m2 2.8 years Lifestyle intervention Metformin Placebo Treatment benefits? Diabetes Prevention Program Research Group 346 (6): 393, Figure 2 February 7, 2002 Treatment benefits? Goal weight loss: 7% (6.6kg) Diabetes Prevention Program Research Group 346 (6): 393, Figure 1 February 7, 2002 Treatment benefits? Diabetes Care 28:888-894, 2005 Treatment benefits? Diabetes Care 28:888-894, 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 2000-2500 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: 60-80 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 SCGH prescriptions for Xenical and Sibutramine 6 months therapy Xenical (n=8) Sibutramine (n=8) Kg -1kg -4kg HbA1c -0.7% 0% 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