胰島素抵抗糖尿病與冠心病

胰島素抵抗糖尿病與冠心病第一頁，共二十九頁，2022年，8月28日AdaptedfromWorldHealthOrganization.Definition,DiagnosisandClassificationofDiabetesMellitus

anditsComplications.Geneva:WorldHealthOrganization:1999:52.CriteriafortheDiagnosisofDiabetesMellitusandHyperglycemia

PlasmaGlucoseConcentration>7.0(>126)

>6.1(>110)to<7.0(<126)2-HourPost

GlucoseLoadFasting

GlucoseDiabetesMellitusImpairedGlucoseToleranceImpairedFastingGlucose>11.1(>200)>7.8(>140)to

<11.1(<200)

Valuesaremmol/L(mg/dl)第二頁，共二十九頁，2022年，8月28日DevelopedDevelopingPercentKingHetal.DiabetesCare1998;21:1414-1431.World1995PrevalenceofDiabetesinAdultPopulation

(Aged>20years)byYearandRegion20002025第三頁，共二十九頁，2022年，8月28日HospitalizationCostsforChronicComplicationsofDiabetesintheUSAmericanDiabetesAssociation.EconomicConsequencesofDiabetesMellitus

intheUSin1997.Alexandria,VA:AmericanDiabetesAssociation,1998:1-14.Totalcosts12billionUS$CVDaccountsfor64%oftotalcostsOthersOphthalmic

diseaseCardiovascular

diseaseRenal

diseaseNeurologic

diseasePeripheral

vascular

disease第四頁，共二十九頁，2022年，8月28日AnnualCHDDeathsper1000PersonsKannelWB,McGeeDL.JAMA1979;241:2035-2038.FraminghamStudy:DMandCHDMortality

20-YearFollow-up178174MenWomenDMNon-DM第五頁，共二十九頁，2022年，8月28日Ischemic

heart

disease%ofDeathsGeissLSetal.In:DiabetesinAmerica.2nded.1995;chap11.MortalityinPeoplewithDiabetes

CausesofDeathOther

heart

diseaseDiabetesCancerStrokeInfectionOther第六頁，共二十九頁，2022年，8月28日Mortalityper1000

person-years**Age-adjustedAdaptedfromGuKetal.DiabetesCare1998;21:1138-1145.MortalityDuetoHeartDiseaseinMenandWomenwithorwithoutDiabetes(US)29.919.2MenWomenDiabetesNoDiabetesAllheartdiseaseIschemicheartdiseaseMenWomen11.56.323.07.111.03.6第七頁，共二十九頁，2022年，8月28日NondiabetesDiabetes*Definedin1971-1975,followedupthrough1982-1984.

**Definedin1982-1984,followedupthrough1992-1993.GuKetal.JAMA1999;281:1291-1297.TrendsinMortalityRatesforIschemicHeartDiseaseinNHANESSubjectswithandwithoutDiabetes*17.06.8-16.6%+10.7%Men,cohort1*Men,cohort2**Women,cohort1*Women,cohort2**-43.8%-20.4%14.27.67.44.22.41.9(P=0.46)(P=0.76)(P<0.001)(P=0.12)Rateper1000person-years第八頁，共二十九頁，2022年，8月28日WOMENMENSurvivalPost-MIinDiabeticandNondiabeticMenandWomen:MinnesotaHeartSurveyAdaptedfromSprafkaJMetal.DiabetesCare1991;14:537-543.1008060400Survival(%)MonthsPost-MINodiabetesn=228n=1628MonthsPost-MISurvival(%)0204060Diabetes100806040080020406080DiabetesNodiabetesn=156n=568第九頁，共二十九頁，2022年，8月28日WOMENMENCardiovascularMortalityinPeople

withDiabetes%ofDeaths(CrudeRate)AdaptedfromMiettinenHetal.DiabetesCare.1998;21:69-75.DiabetesNoDiabetes28.622.110.911.9DiabetesNoDiabetes15.49.622.79.09.14.211.12.828d–1yHospitalization–28dOutofHospital第十頁，共二十九頁，2022年，8月28日InfluenceofMultipleRiskFactors*onCVDDeathRatesinDiabeticandNondiabeticMen:MRFITScreeneesNoneOneonlyAge-adjustedCVDdeathrateper10,000person-years*Serumcholesterol>200mg/dl,smoking,SBP>120mmHgStamlerJetal.DiabetesCare1993;16:434-444AllthreeNodiabetesDiabetesTwoonly第十一頁，共二十九頁，2022年，8月28日PutativeMechanismforIncreasedAtherosclerosisinType2DiabetesBLACKBOXDyslipidemiaHypertensionHyperinsulinemia/insulinresistanceHemostaticabnormalitiesHyperglycemiaAGEproteinsOxidativestressAGE=advancedglycationendproductsAdaptedfromBiermanEL.Arterioscler

Thromb1992;12:647-656.第十二頁，共二十九頁，2022年，8月28日+=moderatelyincreasedcomparedwithnondiabeticpopulation++=markedlyincreasedcomparedwithnondiabeticpopulation–=notdifferentcomparedwithnondiabeticpopulationPrevalenceofCardiovascularRiskFactorsinDiabeticSubjectsRelativetoNondiabeticsType1Dyslipidemia

Hypertriglyceridemia

LowHDL

Small,denseLDL

IncreasedapoBHypertensionHyperinsulinemia/insulinresistanceCentralobesityFamilyhistoryofatherosclerosisCigarettesmokingAdaptedfromChaitA,BiermanEL.In:Joslin’sDiabetesMellitus.Philadelphia:Lea&Febiger,1994:648-664.Type2RiskFactor

+–––+––––

+++++++++++++++–第十三頁，共二十九頁，2022年，8月28日DifferencesinHDLCholesterolandLDLSizebyDiabeticStatusinWomenandMenHowardBVetal.DiabetesCare1998;21:1258-1265.0-2-4-6-8DifferencesbetweenparticipantswithandwithoutdiabetesHDLCholesterolLDLSize?0-2-4-6-8mg/dLWomenMenWomenMen第十四頁，共二十九頁，2022年，8月28日StrategiesforReductionofDiabeticComplicationsMicrovascularcomplications

-Aggressivescreening

-ImprovedmetaboliccontrolMacrovascularcomplications

-Improvedglycemiccontrol(positivebutminor)

-Preventionoftype2diabetes

-AggressivetreatmentofestablishedCVRFin

diabeticandpossiblyprediabeticsubjects

-Diabeticagentsthatimprovecardiovascularrisk第十五頁，共二十九頁，2022年，8月28日IncidenceRatesofMIandMicrovascularEndpointsbyMeanSystolicBloodPressure:UKPDS110120130140150160170Incidenceper1000Person

Years(%)AdlerAIetal.BMJ2000;321:412-419.UpdatedMeanSystolicBloodPressure(mmHg)Adjustedforage,sex,andethnicgroupMyocardialInfarctionMicrovascularEndpoints第十六頁，共二十九頁，2022年，8月28日IncidenceRatesofMIandMicrovascularEndpointsbyMeanHemoglobin

A1c:UKPDS567891011Incidenceper1000Person

Years(%)StrattonIMetal.BMJ2000;321:405-412.UpdatedMeanHemoglobinA1cConcentration(%)Adjustedforage,sex,andethnicgroupMyocardialInfarctionMicrovascularEndpoints第十七頁，共二十九頁，2022年，8月28日PlasmaInsulinandTriglyceridesPredictIschemicHeartDisease:QuebecCardiovascularStudyDespresJPetal.NEnglJMed1996;334:952-957.OddsRatio<1212-15>15F-Insulin(U/ml)4.6p=0.005>150mg/dl<150mg/dlTriglycerides1.01.55.3p=0.001P<0.0016.75.4P=0.002第十八頁，共二十九頁，2022年，8月28日PlasmaInsulinandApolipoproteinBPredictIschemicHeartDisease:QuebecCardiovascularStudyDespresJPetal.NEnglJMed1996;334:952-957.OddsRatio<1212-15>15F-Insulin(U/ml)3.0p=0.04>119mg/dl<119mg/dlApolipoproteinB1.01.53.2p<0.00111.09.7P<0.001p=0.04第十九頁，共二十九頁，2022年，8月28日LDLParticleSizeandApolipoproteinBPredictIschemicHeartDisease:QuebecCardiovascularStudyLamarcheBetal.Circulation1997;95:69-75.>25.64<25.64LDLPeakParticleDiameter(nm)1.01.06.2(p<0.001)ApoB>120mg/dl2.0<120mg/dl第二十頁，共二十九頁，2022年，8月28日BaselineAnthropometricVariablesandCardiovascularRiskFactorsinSubjectswithNormalGlucoseToleranceatBaselineAccordingtoConversionStatusat8-YearFollow-up:SanAntonioHeartStudyBMI(kg/m2)Centrality*TG(mmol)HDLC(mmol)SBP(mmHg)Fastingglucose(mmol)Fastinginsulin(pmol)HaffnerSMetal.JAMA1990;263:2893-2898.28.2+1.11.38+0.091.83+0.121.14+0.07116.8+3.05.28+0.1157+2727.2+0.21.16+0.21.26+0.101.28+0.02108.8+0.85.00+0.0281+5.472.472.006.045.004.032.006ConversionStatusatFollow-upDiabetes(n=18)Normal(n=490)P*Ratioofsubscapulartotricepsskinfolds第二十一頁，共二十九頁，2022年，8月28日“TickingClock”HypothesisWHO.Diabetologia1985;28:615-640;HaffnerSMetal.JAMA1990;263:2893-2898.ForMicrovascularcomplicationsMacrovascularcomplicationsThe“clockstartsticking”Atonsetofhyperglycemia

Beforethediagnosisofhyperglycemia第二十二頁，共二十九頁，2022年，8月28日HemoglobinA1FastingGlucoseThe7-YearAge-AdjustedIncidenceofCHDMortalityandAllCHDEvents:East-WestStudyLehtoSetal.Diabetes1997;46:1354-1359.403020100%IncidenceP-glucose(mmol/L)<9.6>13.4403020100%IncidenceCHDMortalityAllCHDEventsCHDMortalityAllCHDEventsHbA1(%)<8.9>10.7第二十三頁，共二十九頁，2022年，8月28日StepwiseSelectionofRiskFactors*in2693WhitePatientswithType2DiabeteswithDependentVariableasTimetoFirstEvent:UKPDS

VariableLow-DensityLipoproteinCholesterolHigh-DensityLipoproteinCholesterolHemoglobinA1cSystolicBloodPressureSmokingPValue<0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.第二十四頁，共二十九頁，2022年，8月28日CriteriaforAcceptingCardiovascularRiskFactorManagementasSimilarinDiabeticandCHDSubjectsTheriskofvasculardiseaseissimilarindiabeticsubjectswithoutpre-existingvasculardiseaseasinnondiabeticsubjectswithvasculardiseaseGlycemiaalonewillnotcompletelyeliminatetheexcessofCHDriskindiabeticsubjectsLipidinterventionstoreduceCHDcanbeequallyeffectiveindiabeticandnondiabeticsubjects第二十五頁，共二十九頁，2022年，8月28日IncidenceofFatalorNonfatalMIDuringa7-YearFollow-upinRelationtoHistoryofMIinNondiabeticvsDiabeticSubjects:East-WestStudyIncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI18.8HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=