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1、WillaHsueh,M.D.ProfessorofMedicine Chief,DivisionofEndocrinology,Diabetes,andHypertensionUCLADavidGeffenSchoolofMedicineLosAngeles,CaliforniaCardiovascularRiskContinuum:ImplicationsofInsulinResistanceandDiabetesDiabetesisavasculardisease:AngiotensinIIhasbeenimplicatedinboththede
2、velopmentofdiabetesanditscomplicationsDiabetes?Insulin-mediatedglucoseuptakeSkeletalmuscleAdipose?FFA?InflammatoryAdipokinesLiver?GlucoseproductionPancreas?InsulinproductionAtherosclerosisCAD,?Stroke,?PeripheralvasculardiseaseDiabeticNephropathy?AlbuminexcretionDiabeticRetinopat
3、hy?VEGF??neovascularizationDiastolicdysfunction,interstitialfibrosis?heartfailureCardiomyopathy?????????IL6PAI-1TNF?adiponectinleptinInsulinsensitivityinsulinresistanceVascularinflammationendothelialdysfunctionangiotensinogenFFAAdipocyteAdipokinesMediateInsulinResistanceandInfla
4、mmationProgressionofAtherosclerosisinInsulinResistanceEndothelialDysfunctionTG,HDL-CsdLDL-CHypertensionUricAcidPAI-1InflammationThrombosisOxidationAtherosclerosisAtherosclerosisUnstableplaqueInflammation,FibrosisCapThrombosisandRuptureEventHyperinsulinemiaMetabolicSyndromeImpair
5、edGlucoseToleraneType2DiabetesHsuehWA,LawR.AJC,2003InsulinResistanceForindividualsbornin2000:Males–32.8%Females–38.5%Estimatedlossoflifeexpectancyifdiagnosedatage40:Males–11.6yearsFemales–14.3yearsNarayanJAMA2003LifetimeRiskforDiabetesintheUS13NH313NH313NH3Dipyridamole(0.56mg/kg
6、)135’RestQuinonesetalAnnInternMed.,2004;140:700-8NoninvasiveMeasurementsof MyocardialBloodFlow:PositronEmissionTomography0’25’45’70’90’115’CPTDIPApproachesthatImproveCoronaryVasomotorFunctioninInsulinResistance:Insulinsensitizers:TZDs,PPAR?ligandsAT1receptorblockers:ARBsGlucosec
7、ontrolintype2diabetes:MetforminVALUE(ValsartanAntihypertensiveLong-TermUseEvaluation):23%lessnewonsetdiabeteswithvalsartancomparedtoamlodipineinpatientswithhypertensionHOPE(HeartOutcomesPreventionEvaluation):32%lessnewonsetdiabeteswithramiprilcomparedtoplaceboinhighcardiovascula
8、rriskpatientsLIFE(LosartanInterventionforEndpoi
