Treatment of Obesity: Treatment of Obesity Goal of treatment: 10% weight loss Caloric restriction: -500 kcal/day Moderate physical activity 30 minutes daily Behavioral modification Drug therapy National Institutes of Health. Obes Res. 1998; 6 (suppl 2): 51S–209S.


Treat Consequences of Obesity: Treat Consequences of Obesity Insulin resistance (DPP, UKPDS, Proactive) Dyslipidemia Hyperglycemia (A1candlt; 7%) Hypertension Prothrombotic state Proinflammatory state  Weight, Activity (lifestyle) andamp; Metformin, TZDs Lifestyle andamp; Statins, Fibrates Lifestyle andamp; Insulin, secretagogues, metformin, TZDs, incretin mimetics Lifestyle andamp; ACEI, ARB, BB, CCBs, diuretics Lifestyle andamp; ASA Lifestyle andamp; statins, TZDs, ACEI/ARB, TG drugs


Treatment of Insulin Resistance: Treatment of Insulin Resistance Abdominal Obesity Insulin Resistance Weight Reduction Physical Activity T2DM ASCVD UKPDS andamp; Proactive DPP TZDs Metformin


Treatment of IndividualMetabolic Risk Factors: Treatment of Individual Metabolic Risk Factors Rx Atherogenic Dyslipidemia Elevated Blood Pressure Glucose Intolerance Proinflammatory State Prothrombotic State


Slide5: Increasing Prevalence (%) of the Metabolic Risk in US Women* ( ≥ 20 y) Ford, ES et al. Diabetes Care 27:2444, 2004 *ATP III Metabolic Syndrome (3+ metabolic risk factors)


NHANES III: Age-Adjusted Prevalence of ³3 Risk Factors (Metabolic Syndrome*): NHANES III: Age-Adjusted Prevalence of ³3 Risk Factors (Metabolic Syndrome*) *Criteria based on ATP III; diabetics were included in diagnosis Ford ES et al. JAMA. 2002;287:356-359. % 24.8 16.4 28.3 22.8 25.7 35.6 0 5 10 15 20 25 30 35 40 White African-American Mexican-American Men Women 25.7% higher 56.7% higher


Preventing Diabetes: Results from the Diabetes Prevention Program: Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403. Cumulative Incidence (%) Years from Randomization Metformin Placebo (n=1082) Placebo Lifestyle Metformin (n=1,073, Pandlt;0.001 vs. placebo) Lifestyle (n=1,079, Pandlt;0.001 vs. metformin, Pandlt;.001 vs. placebo) Risk Reduction 31% by metformin 58% by lifestyle Preventing Diabetes: Results from the Diabetes Prevention Program 0 10 20 30 40 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5


Except for Diabetes, CV Risk Factors Have Declined Over the Past 40 Years: Except for Diabetes, CV Risk Factors Have Declined Over the Past 40 Years Gregg EW et al. JAMA. 2005;293:1868-1874 30 40 High total cholesterol (240 mg/dL) High blood pressure (systolic andgt;140 mm Hg or diastolic andgt;90 mm Hg) Smoking Total diabetes (diagnosed/ undiagnosed) Diagnosed diabetes Prevalence (%) 0 3 6 9 12 Prevalence (%)


Slide9: The Steno-2 Study 85 CVD events in 35 conventional patients (44%) versus 33 CVD events in 19 intensive patients (24%) 12 24 36 48 60 72 84 96 0 Hazard ratio 0.47 (0.24 to 0.73); p=0.007 Conventional Intensive 0.0 0.1 0.2 0.3 0.4 0.5 0.6 Months of Study Probability for Primary Composite End Point Residual CV Risk After Intensive Multiple Risk Factor Therapy Gaede P et al. N Engl J Med. 2003;348:383-393.


Slide10: Lifestyle + intensive management of glycemia, hypertension, dyslipidemia, microalbuminuria, risk of thrombosis CV Event Rate (%) Gaede P et al. N Engl J Med. 2003;348:383-393. HR 0.47 (0.24 to 0.73) 44 24 0 10 20 30 40 50 Conventional Therapy Intensive Therapy Residual CV Risk After Intensive Multiple Risk Factor Therapy Steno-2 Reveals The Therapeutic Gap in Type 2 Diabetes


Association of MI* With the Metabolic Syndrome and Individual Components: Association of MI* With the Metabolic Syndrome and Individual Components Odds Ratio 95% CI P Value Metabolic syndrome 2.01 1.53-2.64 andlt;0.0001 Syndrome components Abdominal obesity 1.15 0.86-1.54 0.3475 High triglycerides 1.51 1.04-2.20 0.0311 Low HDL-C 1.41 1.03-1.95 0.0353 Hypertension 1.42 0.94-2.15 0.0947 Insulin resistance† 1.25 0.92-1.71 0.1461 *Self-reported. †Fasting plasma glucose ³110 mg/dL. Ninomiya JK et al. Circulation. 2004;109:42-46. Third National Health and Nutrition Examination Survey.


Impact of Weight Loss on Risk Factors: Impact of Weight Loss on Risk Factors 1. Wing RR et al. Arch Intern Med. 1987;147:1749-1753. 2. Mertens IL, Van Gaal LF. Obes Res. 2000;8:270-278. 3. Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S. 4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:264-270. 1 2 3 3 1 2 3 3 4


Summary: Summary Abdominal adiposity causes disability and death especially through DM andamp; CVD risk. Adipokines mediate much of this effect through a complex network of mechanisms on several organs. Recognition and treatment is imperative. Lifestyle is key. Drug treatment to affect causes and consequences of abdominal adiposity is also needed.


Identifying patients at elevated cardiometabolic risk: Identifying patients at elevated cardiometabolic risk Many patients at high CV risk can be identified by a simple waist circumference measurement in conjunction with other routine cardiometabolic markers High waist circumference, a marker of abdominal obesity: is an independent CV risk factor is independently associated with each of the other components of the metabolic syndrome Waist circumference measurement should become a routine part of global assessment of metabolic and cardiovascular risk and should be integrated into standard clinical practice Pouliot MC et al. Am J Cardiol. 1994;73:460-8. Carr MC andamp; Brunzell JD. J Clin Endocrinol Metab. 2004;89:2601-7.


Assess and Manage Obesity: Assess and Manage Obesity If you only have 15 minutes…. Tell your patients that you are concerned about his/her weight. You can start this discussion by saying, 'I’m concerned about your weight because I think it is causing or will cause health problems for you. Do you think your weight is causing problems for you?' Advise you patient to lose weight. First ask, 'Have you ever tried to lose weight?' Praise your patient’s efforts, and reinforce that weight management through increasing physical activity and watching what one eats is good for health. If your patient is interested in weight management, share handouts for him/her to read at home. Some handouts that you can share are the Graphing Your Weight Gain chart, the Eating Pattern questionnaire, and the Weight Loss Questionnaire. Assessment and Management of Adult Obesity: A Primer for Physicians, AMA


DM and CHD Mortality: Kannel WB, McGee DL. JAMA 1979;241:2035-2038. DM and CHD Mortality Annual CHD Deaths per 1000 Persons Framingham Study: 20-Year Follow-up 0 2 4 6 8 10 12 14 16 18


Metabolic Syndrome: Prevalence of ATP III Criteria (NHANES III) by Age: Metabolic Syndrome: Prevalence of ATP III Criteria (NHANES III) by Age Overall 22% for age 20 years and older (N= 8,814 US adults) Age, years Ford ES, et al. JAMA. 2002;287(3):356-359. Park et al. Arch Intern Med. 2003;163:427-436