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1、Medical Complications of Obesity,BMI-Associated Disease Risk,Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. Obes Res 1998;6(suppl 2).,Additi

2、onal risks:Large waist circumference (men>40 in; women >35 in)5 kg or more weight gain since age 18-20 yPoor aerobic fitnessSpecific races and ethnic groups,Weight (lb),Body Mass Index Chart,,Relationship Betwe

3、en BMI and Percent Body Fat in Men and Women,Adapted from: Gallagher et al. Am J Clin Nutr 2000;72:694.,Body Fat (%),Body Mass Index (kg/m2),0,10,30,40,60,20,50,WomenMen,,,Pulmonary diseaseabnormal functionobstructive

4、 sleep apneahypoventilation syndrome,Nonalcoholic fatty liver diseasesteatosissteatohepatitiscirrhosis,Coronary heart disease Diabetes Dyslipidemia Hypertension,Gynecologic abnormalitiesabnormal mense

5、sinfertilitypolycystic ovarian syndrome,Osteoarthritis,Skin,Gall bladder disease,Cancerbreast, uterus, cervixcolon, esophagus, pancreaskidney, prostate,Phlebitisvenous stasis,Gout,Medical Complications of Obesity,,

6、Idiopathic intracranial hypertension,Stroke,Cataracts,,,,,,,,,,,,,,,,Severe pancreatitis,,,Metabolic Syndrome,Abdominal obesityHyperinsulinemiaHigh fasting plasma glucoseImpaired glucose toleranceHypertriglyceridemia

7、Low HDL-cholesterolHypertension,,,Evolution of Metabolic Syndrome,Isomaa B et al. Diabetes Care. 2001;24:683-689.,AKA: Insulin Resistance Syndrome; Syndrome X; Dysmetabolic Syndrome; Multiple Metabolic Syndrome,,1923:

8、Kylin describes clustering of hypertension, gout, and hyperglycemia,,1988: Reaven describes “Syndrome X” – hypertension, hyperglycemia, glucose intolerance, elevated triglycerides, and low HDL cholesterol,,,1998: World H

9、ealth Organization defines “metabolic syndrome” as clustering of hypertension, low HDL, hypertriglyceridemia, insulin resistance, glucose intolerance or type 2 diabetes, high waist-to-hip ratio, and microalbuminuria,,,Ab

10、dominal obesity Glucose intolerance/ Insulin resistance Hypertension Atherogenic dyslipidemiaProinflammatory/Prothrombotic state,Characteristics of the Metabolic Syndrome: NCEP-ATP III,National Cholesterol Educatio

11、nal Program (NCEP), Adult Treatment Panel (ATP) III; 2001.,Diabetes,CVD,Clinical Identification of the Metabolic Syndrome*: NCEP-ATP III,*Diagnosis is established when >3 of these risk factors are present,Expert Panel

12、 on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.,** 2003 New ADA IFG criteria (Diabetes Care),,,Increasing Prevalence of NCEP Metabolic Syndrome with Age (NHANES III

13、),Prevalence (%),Age,Men Women,,,Ford E et al. JAMA. 2002;287:356-359.,,,,Prevalence of CHD by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+,CHD Prevalence,No MS/No DM,8.7%,% of Popul

14、ation = 54.2% 28.7% 2.3% 14.8%,Alexander C, et al. Diabetes 52: 1210-1214, 2003,13.9%,7.5%,19.2%,MS/No DM,DM/No MS,DM/MS,,Prevalence of the Metabolic Syndrome Varies by Sex and Race/Ethnicity

15、 (NHANES III),Prevalence (%),Age,Ford E et al. JAMA. 2002;287:356-359.,25%,16%,28%,21%,23%,26%,36%,20%,Metabolic Syndrome: Impact on Mortality,,Mortality Rate (%),Without metabolic syndromeWith metabolic syndrome,,*,Iso

16、maa B et al. Diabetes Care. 2001;24:683-689.,*P < 0.001.,*,,Metabolic Syndrome: Impact on Cardiovascular Health,,Prevalence (%),Without metabolic syndromeWith metabolic syndrome,,*,*P < 0.001.,,Isomaa B et al. Dia

17、betes Care. 2001;24:683-689.,*,*,,Elevated Risk of CVD Prior to Clinical Diagnosis of Type 2 Diabetes,Relative Risk,1.00,Nondiabeticthroughoutthe study,Hu FB et al. Diabetes Care. 2002;25:1129-1134.,Prior todiagnosis

18、of diabetes,After diagnosisof diabetes,Diabetic atbaseline,2.82,3.71,5.02,Characteristics of Metabolically Normal Obese and Metabolically Abnormal Obese Subjects?,?Postmenopausal women.*P = 0.03; **P = 0.0001.LBM =

19、lean body mass.AT = adipose tissue.,Brochu M et al. J Clin Endocrinol Metab. 2001;86:1020-1025.,Lipids and Lipoproteins & Resting BP in Insulin-Sensitive and Insulin-Resistant Obese Subjects?,?Postmenopausal women.

20、Data are mean ? SD. *P = 0.01.,Brochu M et al. J Clin Endocrinol Metab. 2001;86:1020-1025.,Oral Glucose Tolerance in Insulin-Sensitive and Insulin-Resistant Obese Subjects?,?Postmenopausal women.?n = 12, sensitiv

21、e; n = 23, resistant.Data are mean ? SD.*P = 0.01; **P = 0.005; ***P = 0.001.,Brochu M et al. J Clin Endocrinol Metab. 2001;86:1020-1025.,,Waist Size vs BMI and the Metabolic Syndrome,8-y Incidence of Metabolic Syndrom

22、e (%),Waist circumference level 2*,,,Han TS et al. Obes Res. 2002;10:923-931.,*Level 2 = waist ?40 inches in men or ?35 inches in women.,,9.98,20.45,19.77,33.43,,Both Insulin Resistance and Decreased Insulin Secretion

23、Predict the Risk of Developing Type 2 Diabetes: 7-Year Incidence,Percent,NeitherLowHigh,Haffner SM et al. Circulation. 2000;101:975-980.,Insulin secretionLowLow,Insulin resistanceHighHigh,BothHighLow,Metabolic st

24、atusHOMA-IR? I30-0min/?G30-0min,Distribution by Metabolic Status Among Converters to Type 2 Diabetes(83% of Prediabetic Subjects are Insulin Resistant),Haffner SM et al. Circulation. 2000;101:975-980.,,Both (54%),(n =

25、 195),Low insulin secretion; insulin sensitive (15.9%),Neither (1.5%),Insulin resistant;good insulinsecretion (28.7%),,,Insulin Resistance (HOMA-IR Quintiles) are Related to CV Disease: San Antonio Heart Study,Increasi

26、ng Insulin Resistance,A: adjusted for age, sex, and ethnicity,B: adjusted for age, sex, and ethnicity, LDL, triglyceride, HDL, systolic blood pressure, fasting glucose, smoking, alcohol consumption, and leisure time exer

27、cise,Hanley A et al. Diabetes Care. 2002;25:1177-1184.,A,HOMA IR,,B,Odds Ratio (95% CI),Increasing Risk of CVD,,,P (trend) < 0.0001,,P (trend) < 0.0075,Intra-Abdominal Fat Mass and CHD Risk in Type 2 Diabetes,Adjus

28、ted for BMI, age (continuous), age2, smoking, parental history of myocardial infarction, alcohol consumption, physical activity, menopausal status, hormone replacement therapy, aspirin intake, saturated fat, and antioxid

29、ant score.,Rexrode W et al. JAMA. 1998;280:1843-1848.,P < 0.001 for trend.,Ectopic Lipids and the Metabolic Syndrome,Metabolic syndrome reflects failure of intracellular lipohomeostasis, which prevents lipotoxicity in

30、 organs of overnourished individualsNormal individuals: lipohomeostasis (ie, lipid overload confined to white adipocytes, designed to store surplus calories)Obese individuals: adipocytes increase leptin secretion in an

31、 attempt to enhance oxidation of surplus lipid in nonadipocytesDeficiency or nonresponsiveness to leptin prevents these protective events and results in ectopic accumulation of lipidsPancreatic ?-cells and myocardiocyt

32、es are “cellular victims” – leading to type 2 diabetes and lipotoxic cardiomyopathy,Unger RH. Endocrinology. 2003.,,,,Relationship Between BMI and Cardiovascular Disease Mortality,Relative Risk of Death,Body Mass index,&

33、lt;18.5,MenWomen,Calle et al. N Engl J Med 1999;341:1097.,18.5–20.4,20.5–21.9,22.0–23.4,23.5–24.9,25.0–26.4,26.5–27.9,28.0–29.9,30.0–31.9,32.0–34.9,35.0–39.9,>40.0,,,,,,,,Lean,Overweight,Obese,,Re

34、lationship Between BMI and Risk of Type 2 Diabetes,Chan J et al. Diabetes Care 1994;17:961.Colditz G et al. Ann Intern Med 1995;122:481.,Age-Adjusted Relative Risk,Body Mass index (kg/m2),MenWomen,,,1.0,2.9,1.0,4.3,1.0

35、,5.0,1.5,8.1,2.2,15.8,4.4,27.6,40.3,54.0,93.2,6.7,11.6,21.3,42.1,,Waist-HipRatioTertile,Abdominal Fat Distribution Increases the Risk of Coronary Heart DiseaseThe Iowa Women’s Health Study,Folsom et al. Arch Intern Me

36、d 2000;160:2117.,Relative risk,Body Mass Index Tertile,2,1,3,3,2,1,,Relationship Between Weight Gain in Adulthood and Risk of Type 2 Diabetes Mellitus,Relative Risk,Weight Change (kg),Willett et al. N Engl J Med 1999;341

37、:427.,,,MenWomen,,,,,,,,,,,,,,,,,Direct Cost * of Chronic Diseases in the United States,Direct Cost ($ Billions),Type 2Diabetes,Wolf AM, Colditz GA. Obes Res. 1998;6:97-106.Hodgson TA, Cohen AJ. Med Care. 1999;37:994-

38、1012.,*Adjusted to 1995 dollars.,Obesity,CoronaryHeart Disease,Hyper-tension,Stroke,$18.1,$18.4,$38.7,$51.6,$53.2,,Effect of Obesity on Expected Lifetime Medical Care Costs* in Men,Costs ($)*,Body Mass Index (kg/m2),32.

39、5,27.5,37.5,55-64,45-54,*Total cost of CHD, type 2 DM, hypertension, hypercholesterolemia, stroke,Age (y),Thompson et al. Arch Intern Med 1999;159:2177.,35-44,22.5,,Increase in Healthcare Costs Among Obese Compared with

40、Lean (BMI <25 kg/m2) Patients*,Increase in Cost Compared with Lean Subjects (%),BMI 30-34 kg/m2,BMI >35 kg/m2,Quesenberry CP Jr et al. Arch Intern Med. 1998;158:466-472.,*HMO Setting: Northern California Kaiser Per

41、manente.,,,,Economic Effect of Obesity to Business: 3-Year Costs to First Chicago NBD,Burton et al. J Occup Environ Med 1998;40:786.,*BMI >27.8 kg/m2 in men; >27.3 kg/m2 in women.,Absenteeism,Healthcare,LeanObese*

42、,,,$4,496,$6,822,$683,$1,546,Annual Medical Expenditures Attributable to Obesity in US,New study quantifying state-level expendituresModel developed to predict expenditures by combining MEPS and BRFFS dataObesity preva

43、lence for US estimated at 20% of total adult populationPrevalence varies considerably by stateOverall range: 15% (CO) – 25% (WV),Finkelstein, et al Obes Res. 2004; 12:18-24.,MEPS = 1998 Medical Expansion SurveyBRFSS =

44、 Behavioral Risk Factor Surveillance System,Annual Medical Expenditures Attributable to Obesity in US,6% total adult medical expenditures are attributable to obesityRange: 4% (AZ, CT) – 7% (AK)7% Medicare expenditures

45、Range: 4% (AZ) – 10% (DE)11% adult Medicaid expendituresRange: 8% (RI) – 16% (IN),Finkelstein, et al Obes Res. 2004; 12:18-24.,Annual Medical Expenses Attributable to Obesity in Selected States,Finkelstein, et al Obes