Conceptual Framework for the Metabolic Syndrome Environmental causes are responsible for the epidemic of the metabolic syndrome (NCEP)Treatment: reduce obesity and increase activity Insulin resistance is the underlying cause of the metabolic syndrome (WHO)Treatment: a) reduce obesity and increase activity b) insulin sensitizers Inflammation is the underlying cause of the metabolic syndromeTreatment: a) reduce obesity and increase activity b) insulin sensitizers c) statins, ACE Inhibitors, ARBs第1頁/共30頁Metabolic Syndrome Increases Risk for CHD and Type 2 DiabetesExpert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.第2頁/共30頁The Metabolic Syndrome:Historical PerspectiveReaven G. Diabetes. 1988;37:1565-1607. HDL-CHypertension第3頁/共30頁The Metabolic Syndrome:Current PerspectiveAdapted from Reaven G. Drugs. 1999;58 (suppl):19-20HemodynamicNovel RiskFactors第4頁/共30頁ATP III: The Metabolic Syndrome*Diagnosis is established when 3 of these risk factors are present* The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.*The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160-3167, 2003Risk FactorDefining LevelAbdominal obesity(Waist circumference) Men102 cm (40 in) Women88 cm (35 in)TG150 mg/dLHDL-C Men40 mg/dL Women130/85 mm HgFasting glucose110 (100)*mg/dL* 2003 New ADA IFG criteria (Expert Panel,Diabetes Care 26:3160-3167, 2003)第5頁/共30頁WHO Metabolic Syndrome Definition 1999:Based on Clinical Criteria Insulin resistance (type 2 diabetes, IFG, IGT)* Plus any 2 of the following: Elevated BP (140/90 or drug Rx) Plasma TG 150 mg/dl HDL 35 mg/dl (men); 30 and/or W/H 0.9 (men), 0.85 (women) Urinary albumin 20 mg/min; Alb/Cr 30 mg/gWHO. Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva: WHO, 1999.* Note that 1999 WHO uses hyperinsulinemic euglycemic clamp whereas 1998 WHO and EGIR use HOMA-IR.第6頁/共30頁IRS: AACE Criteria第7頁/共30頁IRS: AACE Criteria Risks (Choose 1) BMI 25 kg/m2 Waist circumference Men 40” Women 35” Sedentary Lifestyle Age 40 Non-Caucasian ethnicity Family History of DM, HTM, or CVD History of glucose intolerance or gestational diabetes Personal Dx of HTN, TGL, low HDL or CVD Acanthosis nigricans Polycystic ovarian syndrome (PCOS) Nonalcoholic fatty liver disease (NAFLD) Cancer (obesity related)第8頁/共30頁IRS: AACE Criteria Parameters (Choose 2) Triglycerides 150 mg/dl HDL cholesterol Men 40 mg/dl Women 135/85 Blood glucose 2-hour 140 mg/dl, OR Fasting 110 125 mg/dl第9頁/共30頁4049Age, years2029505970Ford ES et al. JAMA 2002;287:356-359.Prevalence, %MenWomenPrevalence of the NCEP Metabolic Syndrome: NHANES III by Age第10頁/共30頁Ford ES et al. JAMA 2002;287:356-359.WhiteAfrican American25%Prevalence of the NCEP Metabolic Syndrome: NHANES III by Sex and Race/EthnicityMenWomen16%28%Mexican AmericanOther21%23%26%36%20%第11頁/共30頁DM(n=1,430)NGT(n=1,808)IFG/IGT(n=685)All(n=3,928)Isomaa B et al. Diabetes Care. 2001;24:683-689.Prevalence of CHD (%)YesNoP=.04Botnia StudyPrevalence of CHD in Patients with the Metabolic Syndrome9.2%Metabolic Syndrome4.1%11.0%5.3%27.1%P=.06P.00113.5%21.4%P.0015.5%第12頁/共30頁Cardiovascular Disease Mortality Increased in the Metabolic Syndrome: Kuopio Ischemic Heart Disease Risk Factor StudyLakka HM et al. JAMA 2002;288:2709-2716.Cumulative Hazard, %026812Follow-up, yearMetabolic Syndrome:Cardiovascular Disease MortalityRR (95% CI), 3.55 (1.986.43)410第13頁/共30頁Prevalence of CHD by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+CHD Prevalence% of Population =No MS/No DM54.2%MS/No DM28.7%DM/No MS2.3%DM/MS14.8%8.7%13.9%7.5%19.2%Alexander CM et al. Diabetes 2003;52:1210-1214.第14頁/共30頁NCEP vs WHO Metabolic Syndrome in Relationship to CVD Mortality: San Antonio Heart Study n = 2,815 (age 25-64) Both NCEP and WHO metabolic syndrome, 509 NCEP alone, n=197 WHO alone, n=199 12.7 year follow-up (229 deaths) Three populations considered Overall population No CVD at baseline No CVD or diabetes at baseline (primary prevention)Hunt, K (Circulation, 2004; 110:1245-1251)第15頁/共30頁Hazard Ratio for CVD Mortality (SAHS): Adjusted for Age, Sex and EthnicityHunt, K (Circulation, 2004; 110:1245-1251)Baseline StatusNCEPWHOGeneral Population2.53 (1.74, 3.67)1.63 (1.13, 2.36)No CVD2.71 (1.74, 4.20)1.63 (1.06, 2.52)No CVD or DM2.01 (1.13, 3.57)0.74 (0.37, 1.48)第16頁/共30頁Hazard Ratio for CVD Mortality (SAHS): Adjusted for Age and Ethnicity 1: No CVD at BaselineHunt, K (Circulation, 2004; 110:1245-1251)WomenMenNCEP3.93 (1.83, 8.28)1.81 (0.72, 1.57)WHO2.70 (1.36, 5.37)1.15 (0.65, 2.06)第17頁/共30頁Hazard Ratio for CVD Mortality (SAHS): Adjusted for Age and Ethnicity 1: No CVD at BaselineHunt, K (Circulation, 2004; 110:1245-1251)Baseline StatusWomenMen1. No DM, No NCEP MS1.001.002. No DM, Yes NCEP MS2.07 (0.72, 6.00)1.96 (0.99, 3.88)3. Yes DM, No NCEP MS3.53 (0.75, 16.7)2.34 (0.70, 7.82)4. Yes DM, Yes NCEP MS8.19 (3.51, 19.1)3.09 (1.49, 6.43)第18頁/共30頁Different Components of the NCEP Metabolic Syndrome Predict CHD: NHANESVariableOddsRatioLower 95%LimitUpper 95%LimitWaist circumference1.130.851.51Triglycerides1.120.711.77HDL cholesterol*1.741.182.58Blood pressure*1.871.372.56Impaired fasting glucose0.960.601.54Diabetes*1.551.072.25Metabolic syndrome0.940.541.68*Significant predictors of prevalent CHDCopyright 2003 American Diabetes AssociationFrom Diabetes, Vol. 52, 2003; 1210-1214Reprinted with permission from The American Diabetes Association.第19頁/共30頁Incident Diabetes after Stratification by Age or BMI, IGT, and the Metabolic SyndromeRef. Lorenzo et al, Diabetes Care, 2003, 26: 3153-3159 NCEPdefinition%YesNoNoYesIGT第20頁/共30頁BMI per kg/m2HDL-C per mg/dl decreaseSBP per mm HgFPG per mg/dlDifferent Components of the NCEP Metabolic Syndrome Predict Diabetes: San Antonio Heart StudyStern MP et al. Ann Intern Med 2002;136:575-581.第21頁/共30頁Comparison of NCEP and 1999 WHO Metabolic Syndrome to Identify Insulin-Resistant Subjects: IRAS% in Lowest Quartile of SiHanley AJ et al. Diabetes 2003;52:2740-2747.OverallHispanicsNon-Hispanic whitesAfrican AmericansNeitherNCEP OnlyWHO OnlyBoth第22頁/共30頁Treatment of the Metabolic Syndrome in Overweight or Obese PatientsWeight loss induced by diet and increased physical activity is the cornerstone of therapy Weight loss induced by drug therapy can also improve specific features of the metabolic syndromeBariatric surgery is the most effective weight loss therapy for extremely obese subjects and improves all features of the metabolic syndrome第23頁/共30頁Treatment of Metabolic Syndrome in Patients with Diabetes80-85% of diabetic subjects in North America and Europe have the metabolic syndromeHowever, most subjects with the metabolic syndrome do not have diabetesStatin therapy (4S, HPS, CARE, CARDS) is effective in diabetic subjectsBlood pressure therapy is (UKPDS, SYST-Euro, HOT) is effective in diabetic subjects第24頁/共30頁Treatment of Specific Clinical Features of the Metabolic SyndromeNo randomized clinical trials on hypertension therapy have presented subgroup analysis on non-diabetic subjects with the metabolic syndromeLipid therapy in the metabolic syndromeStatin therapy, positive 4S (Pyorala, Diabetes Care, 2004)Statin therapy not significant in other statin trials (HPS, ASCOT, WOSCOPS) but no evidence of heterogeneityNone of these studies used contemporary definitions第25頁/共30頁NCEP White Paper Introduces concept of very high risk patients with optional LDL-C goal 200 mg/dl plus non-HDL-C 130 mg/dl with low HDL-C 40 mg/dl)Acute coronary syndromeGrundy et al, Circulation, 2004; 110: 227-239.第26頁/共30頁Approaches to Therapy: Metabolic Syndrome Weight loss induced by behavioral therapy (weight loss and increased activity), selected pharmacotherapy, and bariatric surgery Treat existing risk factorsa) Should management be intensified over and above global risk?b) Yes, but probably not CHD risk equivalentUse of insulin sensitizing therapies in nondiabetic subjects with MSa) No for metabolic syndrome alone (no clinical trials)b) Do OGTT three outcomes: 1) DM (treat) 2) IGT 3) NGT (no treatment)c) Perhaps for IGT subjects (clinical trials available DPP, STOP-NIDDM, TRIPOD)第27頁/共30頁Summary: Metabolic Syndrome The metabolic syndrome predicts the development of both diabetes and CHD Insulin resistance and obesity characterize most individuals with the metabolic syndrome, although insulin resistance and obesity are not required features of the NCEP metabolic syndrome Initial therapy for the metabolic syndrome should consist of caloric restriction and increased physical activity Conventional cardiovascular risk factors such as lipids and blood pressure should be treated in individuals with the metabolic syndrome, although no national recommendations have so far suggested intensification of risk factor management No consensus exists on whether insulin sensitizers should be used in nondiabetic individuals with the metabolic syndrome第28頁/共30頁第29頁/共30頁感謝您的觀看！第30頁/共30頁