肥胖和代谢综合征课件

Obesity and Metabolic SyndromeSteven M.Haffner,MD Obesity and Metabolic SyndromConceptual Framework for the Metabolic SyndromelEnvironmental causes are responsible for the epidemic of the metabolic syndrome(NCEP)Treatment:reduce obesity and increase activitylInsulin resistance is the underlying cause of the metabolic syndrome(WHO)Treatment:a)reduce obesity and increase activity b)insulin sensitizerslInflammation is the underlying cause of the metabolic syndromeTreatment:a)reduce obesity and increase activity b)insulin sensitizers c)statins,ACE Inhibitors,ARBsConceptual Framework for the MMetabolic 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.Coronary Heart DiseaseType 2DiabetesHighLDL-CMetabolicSyndromeMetabolic Syndrome Increases RThe Metabolic Syndrome:Historical PerspectiveReaven G.Diabetes.1988;37:1565-1607.InsulinInsulinResistanceResistanceGlucoseGlucoseIntoleranceIntoleranceHyperinsulinemiaHyperinsulinemia TGTG HDL-CHypertension1988:Syndrome X1988:Syndrome XCORONARY HEART DISEASECORONARY HEART DISEASEThe Metabolic Syndrome:HistorThe Metabolic Syndrome:Current PerspectiveAdapted from Reaven G.Drugs.1999;58(suppl):19-20Body SizeBody Size BMI BMI Central Adiposity Central AdiposityGlucoseGlucoseMetabolismMetabolismUric AcidUric AcidMetabolismMetabolismDyslipidemiaDyslipidemiaHemodynamicNovel RiskFactorsCORONARY HEART DISEASECORONARY HEART DISEASEInsulin ResistanceInsulin ResistanceHyperinsulinemiaHyperinsulinemia+l l TGTGl l PP lipemia PP lipemial l HDL-C HDL-Cl l PHLA PHLAl lSmall,dense LDLSmall,dense LDLl l GlucoseGlucoseintoleranceintolerancel l Uric acidUric acidl l Urinary uric Urinary uricacid clearanceacid clearancel l SNS activitySNS activityl l Na retention Na retentionl lHypertensionHypertensionl l CRPCRPl l PAI-1 PAI-1l l FibrinogenFibrinogenThe Metabolic Syndrome:CurrenATP III:The Metabolic Syndrome*Diagnosis is established when*Diagnosis is established when 3 of these risk factors are present3 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)ATP III:The Metabolic SyndromWHO Metabolic Syndrome Definition 1999:Based on Clinical CriterialInsulin resistance(type 2 diabetes,IFG,IGT)*lPlus any 2 of the following:Elevated BP(140/90 or drug Rx)Plasma TG 150 mg/dlHDL 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.WHO Metabolic Syndrome DefinitIRS:AACE CriteriaDiagnosing Insulin Resistance SyndromeIs as Simple as 1 plus 2Choose:One Risk+Two ParametersIRS:AACE CriteriaDiagnosing IIRS:AACE Criteria Risks(Choose 1)lBMI 25 kg/m2lWaist circumferenceMen 40”Women 35”lSedentary LifestylelAge 40lNon-Caucasian ethnicitylFamily History of DM,HTM,or CVDlHistory of glucose intolerance or gestational diabeteslPersonal Dx of HTN,TGL,low HDL or CVDlAcanthosis nigricanslPolycystic ovarian syndrome(PCOS)lNonalcoholic fatty liver disease(NAFLD)lCancer(obesity related)IRS:AACE Criteria Risks(ChIRS:AACE Criteria Parameters(Choose 2)lTriglycerides 150 mg/dllHDL cholesterolMen 40 mg/dlWomen 135/85lBlood glucose2-hour 140 mg/dl,ORFasting 110 125 mg/dlIRS:AACE Criteria Parameter4049202070+70+Age,years20293030393950596060696970Ford ES et al.JAMA 2002;287:356-359.Prevalence,%MenWomen24%24%23%23%8%8%6%6%44%44%44%44%Prevalence of the NCEP Metabolic Syndrome:NHANES III by Age40492070+Age,years2029303Ford 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%Ford ES et al.JAMA 2002;287:3DM(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 SyndromePrevalence 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%DMNGTIFG/IGTAllIsomaa B et al.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,yearYESYESMetabolic Syndrome:NONOCardiovascular Disease MortalityRR(95%CI),3.55(1.986.43)410Cardiovascular Disease MortaliPrevalence of CHD by the Metabolic Syndrome Prevalence of CHD by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+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.Prevalence of CHD by the MetabNCEP vs WHO Metabolic Syndrome in Relationship NCEP vs WHO Metabolic Syndrome in Relationship to CVD Mortality:San Antonio Heart Studyto CVD Mortality:San Antonio Heart Studyln=2,815(age 25-64)Both NCEP and WHO metabolic syndrome,509NCEP alone,n=197WHO alone,n=199l12.7 year follow-up(229 deaths)lThree populations consideredOverall populationNo CVD at baselineNo CVD or diabetes at baseline(primary prevention)Hunt,K(Circulation,2004;110:1245-1251)NCEP vs WHO Metabolic SyndromeHazard 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)Hazard Ratio for CVD MortalityHazard 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)Hazard Ratio for CVD MortalityHazard 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)Hazard Ratio for CVD MortalityDifferent 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 CHDPrediction of CHD Prevalence using Multivariate Prediction of CHD Prevalence using Multivariate Logistic RegressionLogistic RegressionCopyright 2003 American Diabetes AssociationFrom Diabetes,Vol.52,2003;1210-1214Reprinted with permission from The American Diabetes Association.Different Components of the NCIncident Diabetes after Stratification by Age or Incident Diabetes after Stratification by Age or BMI,IGT,and the Metabolic SyndromeBMI,IGT,and the Metabolic SyndromeRef.Lorenzo et al,Diabetes Care,2003,26:3153-3159p0.0001p0.0001p0.0001p0.0001P=0.018P=0.018 NCEPdefinition%YesNoNoYesIGTIncident Diabetes after StratiBMI 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.Risk of Type 2 Diabetes per Unit Change in Risk Trait LevelsRisk of Type 2 Diabetes per Unit Change in Risk Trait Levels8%8%2%2%4%4%7%7%BMI per kg/m2HDL-C per mg/dl dComparison 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 OnlyBothComparison of NCEP and 1999 WHTreatment 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 syndromeTreatment of the Metabolic SynTreatment 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 subjectsTreatment of Metabolic SyndromTreatment 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 definitionsTreatment of Specific ClinicalNCEP 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.NCEP White Paper Introduces cApproaches to Therapy:Metabolic SyndromelWeight loss induced by behavioral therapy(weight loss and increased activity),selected pharmacotherapy,and bariatric surgerylTreat existing risk factorsa)Should management be intensified over and above global risk?b)Yes,but probably not CHD risk equivalentlUse 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)Approaches to Therapy:MetabolSummary:Metabolic SyndromelThe metabolic syndrome predicts the development of both diabetes and CHD lInsulin resistance and obesity characterize most individuals with the metabolic syndrome,although insulin resistance and obesity are not required features of the NCEP metabolic syndromelInitial therapy for the metabolic syndrome should consist of caloric restriction and increased physical activitylConventional 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 managementlNo consensus exists on whether insulin sensitizers should be used in nondiabetic individuals with the metabolic syndromeSummary:Metabolic SyndromeTh演讲完毕，谢谢观看！Thank you for reading!In order to facilitate learning and use,the content of this document can be modified,adjusted and printed at will after downloading.Welcome to download!汇报人：XXX汇报日期：20XX年10月10日演讲完毕，谢谢观看！Thank you for readin