糖尿病预防-西方经验的思考与展望(英文版)

DiabetesPreventionProgram:

USExperience

GlobalDiabetesPandemicIDF2015GlobalDiabetesPandemicIDF2015Theprevalenceofbothtype1andtype2diabetesisincreasing,despitethefactthatmanycasesoftype2diabetescanbedelayedorprevented.ProfessorNamHanCho,

Chair,IDFAtlasCommittee,7thEditionAge-adjustedPercentageofAdultsintheUnitedStatesWhoWereObeseorDiagnosedwithDiabetesDiabetesNoData<4.5%4.5-5.9%6.0-7.4%7.5-8.9%≥9.0%199420002009Obesity(BMI≥30kg/m2)199420002009NoData<14.0%14.0-17.9%18.0-21.9%22.0-25.9%≥26.0%EdelsteinSL,etal.Diabetes1997;46:701-710IncidenceofNIDDMbasedon:Age2hPGFPGBMIWhatweknewabout

riskofdiabetesbeforetheDPPMenWomenFamilyhistoryNoYesRace/ethnicityIFG/IGTType2DMEarlyComplicationsMorbidity/Mortality

102030

Prevention

InterventionInterventionTimeofusualdiagnosisDysglycemia:

PotentialforInterventionCanwepreventordelaythedevelopmentoftype2diabetesinpersonsathighrisk(impairedglucosetolerance,elevatedfastingglucoselevels,andoverweightorobese)?

DPPGoals:PrimaryHigh-riskindividuals2hourglucose140-199mg/dlandFastingglucose95-125mg/dl(AmericanIndians<125mg/dl)Bodymassindex≥24kg/m2(Asians≥22kg/m2)Age≥25yearsAllethnicgroups-goalof50%fromhighriskpopulations

DPPEligibilityCriteriaDPPStudyTreatmentGroupsScreen(n=30,935)Randomize(n=3,819)StandardlifestyleteachingIntensiveLifestyle

(n=1079)Metformin850mgBID

(n=1073)Placebo(n=1082)Troglitazone

(n=585)DPPStudyTreatmentGroupsRandomize(n=3,234)StandardlifestyleteachingIntensiveLifestyle(n=1079)Metformin850mgBID(n=1073)Placebo(n=1082)IntensiveLifestyleIntervention≥7%lossofbodyweightandmaintenanceofweightlossMajorlifestylechangefocusedonreductionofdietaryfat≥150minutesperweekofphysicalactivityBehavioralModificationGoalsLifestyleInterventionCurriculum

First24weeks-16sessioncore(individual)Maintenance-after24weeksIndividualin-personatleastonceper2mo

>1phonecontactbetweenvisits

>3group“courses”peryearCaucasian55%(n=1768)AfricanAmerican20%(n=645)Hispanic16%(n=508)Asian/PacificIslander4%(n=142)AmericanIndian5%(n=171)StudyPopulation25-44yrs31%(n=1000)≥60yrs20%

(n=648)45-59yrs49%(n=1586)AgeandRace/EthnicityDistributionDPPRecruitment1996-1999StudyPopulationBaselineNumber3234Age(y)50.6Women(%)68GDM(%ofwomen)16BMI(kg/m2)34.0FPG(mg/dL)106.52-hPG(mg/dL)164.6HbA1c(%)5.9BaselineCharacteristicsRecruited1996-1999MeanWeightChangefromBaselineYearsfromRandomizationLifestyleMetforminPlacebo7.2%4.2%NEJM2002;346:393-4030

1

2

3

4010203040PlaceboAnnualincidence=11.0%MetforminAnnualincidence=7.8%LifestyleAnnualincidence=4.8%PercentDevelopingDiabetes

AllparticipantsYearsfromRandomizationCumulativeincidence(%)31%reduction58%reductionNEJM2002;346:393-403Trialstoppedoneyearaheadofschedule,afteranaveragefollow-upof2.8years,atrecommendationofDSMBbecause

“ofprovedefficacy”DiabetesIncidenceRatesbySex

NEJM2002;346:393-403AnnualIncidenceRate(%)DiabetesIncidenceRatesbyEthnicityNEJM2002;346:393-403AnnualIncidenceRate(%)DiabetesIncidenceRatesbyAgeP=NSP=0.07fortrendEffectsofAgeonTreatmentResponseAge25-4445-59>60(n=1000)(n=1586)(n=648)

AgeatBaseline71%reductionP=0.007fortrend48%reduction44%reduction11%reductionAnnualIncidenceRate(%)(n=1045)(n=995)(n=1194)DiabetesIncidenceRatesbyBMIBodyMassIndex(kg/m2)NEJM2002;346:393-40365%reduction51%reduction3%reduction53%reductionAnnualIncidenceRate(%)NopriorGDMPriorGDMPlaceboGestationalDiabetesJCEM2008;93:4774MetvsPLBO=51%,P<0.001ReductioninIncidence

ILSvsPLBO=53%,P<0.001ReductioninIncidenceILSvsPLBO=49%,P<0.001METvsPLBO=14%,NSPlacebo(n=487)Placebo(n=122)Metformin(n=111)Metformin(n=464)ILS(n=464)ILS(n=117)

3-yrCumulativeincidence

25.7%

38.4%TCF7L2Genotypeatrs7903146DoesILSinterventionWorkinSettingofHighGeneticRisk?NEJM2006;355:241-25049%41%9%CCCTTTAnnualIncidenceRate(%)Naturevs.Nurture

-15-10-50+505101520Hazardrateper100/yrMeanweightchangefrombaseline(kg)AnnualincidenceataveragestudyweightlossinlifestylegroupDiabetesCare2006;29:2102-2017AnnualDiabetesIncidenceInthelifestylegroup,everykgofweightlosswasassociatedwitha16%reductioninriskofdiabetes.1kg16%EffectofWeightLossonDiabetesIncidenceDiabetesPreventionProgramDPPdemonstratedpowerfuleffectsoflifestyleinterventionandmetformintodelaythedevelopmentofdiabetesinacohortselectedtobeatparticularlyhighrisktodevelopdiabetesInmenandwomenAcrossabroadspectrumofrace/ethnicitiesAcrossagegroups,includingtheelderlyThedesignoftheDPP,withrepresentativepopulations,hasdirectlyfacilitatedwidespreadtranslation.SummaryDiabetesPreventionProgramOutcomesStudy2002-2021(2025?)TheDPPandDPPOutcomesStudy1996DPPRecruitmentBegan1999DPPEnrollmentCompleted2001DPPResults2002DPPOSBegins2009DPPOSMidpointResults2015DPPOS-endDPPOS-3start199720012009MetforminInt.LifestylePlacebo

Grouplifestylewithmetformin

GrouplifestylewithlifestyleBoost

Grouplifestyle20022016InterventionsBRIDGEAllDPPparticipantsofferedgrouplifestyletraining

After2.8y

ofDPPILS vPLBO 58%METvPL BO 31%

OtherBenefitsoverTimewithILS(comparedwithplacebo)LowerHbA1cwithfewermedsLowerBPandlipidlevelswithfewermeds

After10y

DPP/DPPOS34%18%

Lancet2009;374:1677NEJM2002;346:393Long-termDiabetesPreventionRiskReduction

After15y

DPP/DPPOS27%18%

LancetD&E2015;3:866ChangeinCVDRiskFactorsByTreatmentAssignment:Over10yearsyearsDiabeticMed2013;30:46Significantlylessfrequentuseofanti-hypertensiveandlipidloweringmedicationsinlifestylegroup10-yearCostsofTreatmentandOutsideMedicalCareintheDPP/DPPOSDiabetesCare2012;35:723-730CostperQuality-AdjustedLifeYear(QALY)gainedLifestylevs.PlaceboMetforminvs.Placebo$10,760CostsavingLifestyleandmetforminfordiabetespreventioninhighriskadultsisagoodinvestment.Additionalbenefitsmayaccrueifdiabetescomplicationsarepreventedordelayed.WhatWeHaveLearnedDiabetesisnotinevitableinpersonsathighrisk.Lifestyleinterventionandmetforminreduceordelayitsdevelopmentforaslongas15years.TherelativebenefitsofILSandmetforminondiabetesdevelopmentduringDPPhavedecreasedduringDPPOS,owingtothereductioninratesobservedintheplacebogroup.Diabetespreventionwascost-savingwithmetformin,andbothlifestyleandmetforminwerecost-effective.1996-2013

AUniqueandValuableCohort

DPP/DPPOSrepresentsthelongestandlargestrandomizedstudyoftheeffectsoflifestyleinterventionandmetformininapre-diabeticpopulationearlyinthecourseofdysglycemia.MetforminRelatedOutcomesAsthelargestandlongest(>15years)randomizedmetformintrial,DPP/DPPOSisuniquelypositionedtoaddressthelong-termbenefitsandrisksofthiswidelyuseddrug.Evidencesuggeststhatmetforminmayhaveimportantextra-glycemiceffects(e.g.,CVD,cancer).MetformintreatmentinDPP/DPPOSislargelyinanon-diabeticpopulation,thusmayprovidevaluableinsightstothesenon-glycemiceffects.BackgroundTheepidemiccontinuesintheUSwithanestimated27millionwithT2DMandanother86millionathighrisk.UnderstandinghowtopreventordelayT2DMandwhentointervene,withthegoalofreducinglong-termmorbidityandmortalityinacost-effectivemanner,isperhapsthemostimportantpublichealthquestionindiabetes.PublicHealthSignificanceNationalDiabetesEducationProgram/HHSStateProgramsCMSADAConsensusWorkplaceInterventionProgramsHealthSystemProgramsIndianHealthServiceCommunityPrograms(e.g.Y-DPP;UnitedHealthGroup)USDepartmentofVeteransAffairsTranslationalImpactofDPPinUSCongressionally-establishedNationalDiabetesPreventionProgramInternationalProgramsCDCGuidelinesfor

USDiabetesPreventionAmericanDiabetesAssociationAmericanMedicalAssociationUSPreventativeServicesTaskForceProgramsfor

USDiabetesPreventionProgramNIDDK:SmallStepsBigRewards(2002)USCDC:NationalDiabetesPreventionProgramCoverageforIntensiveBehavioralTherapyforObesitybyMedicare(2011)andNationalDPP(2017)ADAStrengthofEvidenceLevelDescriptionAClearevidencefromwell-conducted,generalizable,randomizedcontrolledtrialsthatareadequatelypowered.BSupportiveevidencefromwell-conductedcohortstudiesCSupportiveevidencefrompoorlycontrolledoruncontrolledstudiesEExpertconsensusorclinicalexperienceTimelineforUSDiabetesPrevention1996ADA:AlthoughscreeningmayidentifyIGTasariskfactor,screeningforIGTaloneisnotjustified.”

DiabCare1996;19(Suppl1):S5DPPStart2001DPPend20031yrpostDPPDPPdemonstratedpowerfuleffectsoflifestyleandmetformintodelaydiabetesinpersonsathighrisk.

DPPResearchGroup

NEJM2002;346:393-403

ADA:Inthosewithprediabetes(IFG/IGT),lifestylemodificationshouldbestronglyrecommended(A)2002-1monNEJMADA:Screenfordiabetesinhigh-risk,asymptomatic,undiagnosedadultswithinthehealthcaresetting.(E)InthosewithIFG/IGT,lifestylemodificationshouldbeconsidered(A)