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EffectofaMultifactorialInterventiononMortalityinType2DiabetesG?de,P.,Lund-Anderen,H.,Hans-Henrik,P.,andO.PedersenNEnglJMed2008;358:580-91PeterKarackiGIMJournalClubMarch25,2008DiabetesBackgroundIn2005,U.S.prevalenceofDM=20.8millionpeopleor~7%ofthepopulation6thleadingcauseofdeathintheU.S.in2004Riskofdeathis2xforanindividualwithdiabetesvs.onewithoutitatthesameageFrom1991to2001,theCDCfounda61%increaseindiagnosisofdiabetesDiabetesComplicationsHeartDisease–2-4xdeathratesvs.adultsw/oDMCVA–risk=2-4xhighervs.adultsw/oDMRetinopathy–#1causeofblindnessinadults20-74yoa.Nephropathy–#1causeofCRFNervoussystemdamageAcutehypoglycemiaorhyperglycemiaPeripheralvasculardiseaseComplicationsduringpregnancySteno-2Study:Intensivetherapyvs.conventionaltherapyforDMII(2003)IntensivetherapyBenefits:(n=80)HazardratioConfidenceInterval1.CVDisease0.470.24to0.732.Nephropathy0.390.17to0.873.Retinopathy0.420.21to0.864.Autonomicneuropathy0.370.18to0.79G?deetal.MultifactorialInterventionandCardiovascularDiseaseinPatientswithType2Diabetes.NEJM.2003;348:383-393Steno-2Follow-up:EffectofaMultifactorialInterventiononMortalityinType2Diabetes(2008)Steno-2meanlength=7.8yrsSteno-2f/umeanlength=+5.5yrs“Wherearetheynow?”O(jiān)riginalSteno-IISelectionCriteriaInclusionCriteriaDiabetesper1985WHOcriteriaMicroalbuminuria–30-300mgurinealbuminin≥4of624hcollectionsExclusionCriteriaAge≥65or≤40AstimulatedC-peptide[]<600pmol/L6minafter1mgglucagonstimulationPancreaticinsufficiencyordiabetes2otopancreatitisETOHabuseNon-diabetickidneydiseaseMalignancyLife-threateningdiseasewithdeathexpected≤4yearsStudy

PopulationEndofStenoIIBeginningoff/uStenoIISteno-IITreatmentObjectivesG?deetal.MultifactorialInterventionandCardiovascularDiseaseinPatientswithType2Diabetes.NEJM.2003;348:383-393Steno-IIf/ugoalsforbothgroupsSteno-IIIntensiveTherapyPatientmetw/memberofprojectteam(doctor,nurseordietitian)onaverage4xayear.ACE-I(50mgcaptoprilbid)orARB(losartan50mgbid)150mgASAdailyPerHbA1c–diet/exercise→Metforminand/orgliclazide→NPH+/-Reg.insulinIf↑TC–upto80mgofatorvastatinIf↑TG(>350)–afibratewasaddedSteno-IIIntensiveTherapy(cont)IfHTN–thiazide,CCBs,BB,orACE-I/ARBDailyMVI–Vit.C,D-α-tocopherol,folicacid,+chromepicolinateFat<30%ofdailycalorieintake(saturated<10%)Light-to-mod.exercisex30min3-5x/weekencouragedSmokersorsmokingspouses→smokingcessationclassesSteno-IIf/uEndpoints2oEndpoints1.DeathfromaCVcause2.CVDevents:a.nonfatalCVAb.nonfatalMIc.CABGd.PCI/PVDint.e.amputation3oEndpoints1.Incidentnephropathy2.Development/progression:a.Diabeticretinopathyb.Peripheralneuropathyc.Autonomicneuropathy1oEndpoint=TimetodeathfromanycauseStatisticalAnalysisStatisticalanalysistobeginwhen60patientsor?ofagrouphaddied1o/2oOutcomes–1.Kaplan-Meier–timeto1stevent 2.Treatmentscomparedbylog-ranktest 3.Proportion-hazardsmodel–togeneratehazardratios+CIs3oOutcomes–Proportional-hazardsmodelw/adjustmentforage,durationofdiabetes,sex+microvascularstatusatbaselinetodeterminerelativerisksChangesinmeasuredvalues–1.Analysisofcovariance 2.Mann-WhitneytestResultsVariableIntensive(n=67)Conventional(n=63)P-valueCarbs(%)45.8±5.243.9±5.0<0.01Fat(%)32.6±4.734.3±5.3<0.05FastingBG(mg/dl)160±55(129)170±61(178)?Metformin(%)6637<0.01Sulfonylurea(%)4016<0.05Anyoral(%)8447<0.01Insulin+oral(%)8342<0.01Beta-Blocker(%)1532<0.05Table1Summary:SelectedStenoIIf/uClinicalCharacteristicsClinicalCharacteristics(cont)Fig.2A

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