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控制糖尿病患者心血管危险

的干预治疗策略糖尿病与心血管危险影响心血管危险的因素综合控制的理论与实践CountriesWithHighestNumbersofEstimatedCasesofDiabetesfor2000and2030RankingCountryPeoplewithdiabetes(millions)CountryPeoplewithdiabetes(millions)200020301 India 31.7 India 79.42 China 20.8 China 42.33 U.S. 17.7 U.S. 30.34 Indonesia 8.4 Indonesia 21.35 Japan 6.8 Pakistan 13.96 Pakistan 5.2 Brazil 11.37 RussianFederation 4.6 Bangladesh 11.18 Brazil 4.6 Japan 8.99 Italy 4.3 Pinecones 7.810 Bangladesh 3.2 Egypt1 6.7Total:177million366MILLIONBY2030Type2diabetesandCHD

7-YearIncidenceofFatal/NonfatalMI(EastWestStudy)

IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI18.8HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)3.00.57.83.23.545.020.2Eventsper

100person-yr:P<0.001p<0.001Type2diabetesandStroke

7-YearIncidenceofFatal/NonfatalStroke(EastWestStudy)IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI7.2HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)1.20.33.41.61.919.510.3Eventsper

100person-yr:P=0.01p<0.001PrevalenceofCHDbytheMetabolicSyndromeandDiabetesintheNHANESPopulationAge50+AlexanderCetal.Diabetes2003;52:1210-121425%20%15%10%5%0%NoMS/NoDM8.7%13.9%7.5%19.2%MS/NoDMDM/NoMSDM/MS%ofpopulation= 54.2% 28.7% 2.3% 14.8%CHDPrevalence1.00.90.80.70.60.00246810Follow-up,years#atrisk174214099062828935NometabolicsyndromeMetabolicsyndromelog-rank=45.4p<0.001Event-freesurvivalSchillaciG.JACC.2004;43:1817-1822代谢综合征与心血管危险MlandMicrovascularEndPoints:IncidencebyMeanSystolicBPandHbA1cConcentrationMlMicrovascularandpointsMlMicrovascularandpoints50403020100806040200Adjustedincidenceper1000person-yr(%)110120130140150160170567891011UpdatedmeansystolicBP(mmHg)UpdatedmeanHbA1cconcentration(%)Adjustedincidenceper1000person-yr(%)AdlerAletal.BMJ2000;321:412-419StrationIMetal.BMJ2000;321:405-412MetS和DM患者血脂异常特征游离脂肪酸TGHDL-C

VLDL-C

小而密LDL颗粒氧化LDL-C餐后高脂血症MaleGender-adjustedFemaleReducedriskwithsmall,denseLDL0.1Relativeriskformyocardialinfarction110Increasedriskwithsmall,denseLDLSmall,denseLDLincreases

cardiovascularriskUKPDS

StepwiseSelectionofRiskFactors*inPatientswithType2Diabetes

VariableLDL-CHDL-CHemoglobinA1cSystolicBloodPressureSmokingPValue<0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.Mangagingoverweightintype2diabeticsEffectiveweightmanagementisthefirststepintreatingtype2diabetesWeightloss(kg)infirst12monthsLeanMEJetal.,DiabetMed,1990;7:228-233Lifeexpectancy(years)95%confidenceinterval1816141210800481216Weightlossisdifficulttomaintainbydietandexercisealoneintype2diabetesUKPDS34.Lancet1998;352:354InsulinChlorpropamideGllbenclamideDietaloneMetforminWeightchange(kg)76543210-10246810YearsfromrandomisationGoodglycemiccontrolisnotenoughUKPDSGOODGLYCEMICCONTROLMICROVASCULARCOMPLICATIONSSignificantreductionsMACROVASCULARCOMPLICATIONSNosignificanteffectPROACTIVEStudySept.2005,

欧洲糖尿病会议

Pioglitazone

vsPlaceboACCORDStudyActiontoControlCardiovascularriskinDiabetesPrisantLM.JClin

Pharmacol2004;44(4):423-430HbA1c:≤6.0%vs7.0-7.9%

糖尿病患者降压治疗临床试验SHEPALLHATSYST-EURHOPECAPPPHOTNORDILRENAALSTOP-2PRIMEINSIGHTLIFEUKPDS

Majorcardiovascularevents(per100patients-years)inalltreatedhypertensiveandinhypertensivepatientswithdiabetesinrelationtotargetbloodpressuresof90.85,and80mmHg.302520151050808590908580P=0.50fortrendP=0.005fortrendAllhypertensivepatients(n=18790)Hypertensivewithdiabetes(n=1501)TargetbloodpressuregroupsMajorcardiovascularevents/1000patients-yearsHOTStudy:ResultsinPatientswithDMEffectofIntensivevsModerateAntihypertensiveTreatmentonStrokeIncidenceinDiabeticNormotensives Intensive ModerateAchievedBP(mmHg) 128/75 137/81Stroke(%) 1.7 5.4P=0.03Schrieretal.,KidneyInt2002;61:1086CHDPreventionTrialswithStatinsinDiabeticSubjects

SubgroupAnalyses

PrimaryPreventionAFCAPS/TexCAPSSecondaryPreventionCARE4SLIPID4S-ExtendedCHDRisk

Reduction

(overall)DrugNo.LovastatinPravastatinSimvastatinPravastatinSimvastatin43%25%(p=0.05)55%(p=0.002)19%42%(p=0.001)37%23%32%25%32%239586202782483CHDRisk

Reduction

(diabetes)StudyAdaptedfromDownsJRetal.JAMA1998;279:1615-1622;GoldbergRBetal.Circulation1998;98:2513-2519;PyöräläKetal.DiabetesCare1997;20:614-620;TheLong-TermInterventionwithPravastatininIschaemicDisease(LIPID)StudyGroup.NEnglJMed1998;339:1349-1357;HaffnerSMetal.ArchInternMed1999;159:2661-2667.CARDS:主要终点年安慰剂组事件数127立普妥®组事件数83累积危险(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.

37%TrialswithFibratesinPatientswithDiabetesStudyEffectp-valueCommentHelsinkiHeartStudy(gemfibrozil)75%eventsnsPrimaryprevention;

post-hocsubgroupanalysisSENDCAP(bezafibrate)65%events0.01SpecificallyconductedinType2diabetes;post-hocanalysisforIHDVA-HIT(gemfibrozil)24%events0.05Secondaryintervention;pre-plannedsubgroupanalysisDAIS(fenofibrate)40-42%focalangiochanges0.02SpecificallyconductedinType2diabetes;mixedprimaryandsecondaryintervention;angiostudyFIELDStudyFenofibrateInterventionandEventLoweringinDiabetesMazzoneT.AmJCardiol2004;93:27C-31C糖尿病患者心血管危险因素的控制目标★减轻体重★降糖:HbA1c≤7.0%★降压:130/80★调脂:LDL-C1.81mmol/LSteno-2StudyMultifactorialInterventionandCardiovascularDiseaseinPatientswithType2DiabetesGradeP,etal.NENGLJMED2003;348:383-393Steno-2:IntensiveTherapyNEJM2000;342:905-912BasicIntervention脂肪摄入30%饱和脂肪酸摄入10%运动30’35次/wACEIorARB多种维生素AspirinPharmacologyIntervention降糖

metformin

gliclazide

metformin+gliclazide降压

thiazideACEIorARB+CCB

-blocker降脂

statinsSteno-2:TreatmentGoalsVariable ConventionalIntensive Therapy TherapySBP(mmHg) 140130

DBP(mmHg) 8580

Hba1c(%)6.56.5TC(mg/dl)190175

TG(mg/dl)

150150Steno-2ChangeinClinicalVariablesattheEndoftheStudyVariableConventionalIntensivepTherapy TherapySBP(mmHg) -33-1420.001DBP(mmHg)-82-1220.006

Carbohydrates(%)4.80.99.30.9

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