2型糖尿病一级预防 糖尿病高危(IGT)人群的干预

2型糖尿病一级预防糖尿病高危(IGT)人群的干预,中日友好医院李光伟,IDF主席开幕式演讲YESTERDAY,TODAYANDTOMORROWKGMMAlbertiPrevention,PreventionandPrevention,X综合征死亡四重奏（Reaven,1988）（Kaplan,1989）,胰岛素抵抗中心性肥胖糖耐量低减/DM糖耐量低减/DM高胰岛素血症高TG血症高TG血症低HDL-c血症高血压高血压胰岛素抵抗综合征（DeFronzo,1991）代谢综合征（Zimmet,1997）,InsulinResistance,Hypertension,Type2Diabetes,Themetabolicsyndromeofinsulinresistance&cardiovasculardisease,ReducedFibrinolysis,ComplexdyslipidemiaTG,sdLDLHDL,EndothelialDysfunction,ChronicsystemicInflammation,Athero-sclerosis&CHD,VisceralObesity,2型糖尿病一级预防糖尿病高危(IGT)人群的干预历史的回顾大庆糖尿病预防研究的由来当前2型糖尿病预防研究的局限及尚未能解决和正在解决的问题,一.历史的回顾,Preventionisbetterthancure,糖尿病一级预防研究对象干预措施大庆研究IGT生活方式DPPIGT生活方式+双胍DPSIGT生活方式STOP-NIDDMIGT阿卡波糖,大庆研究中糖尿病每百人年发病率,11.5,10.8,11.4,17.2,饮食组,运动组,饮食+运动,对照组,BMI=25,5.1,6.8,13.3,8.3,饮食组,运动组,饮食+运动,对照组,BMI100,例,多因素分析,胰岛素抵抗对干预疗效分析,目的,（大庆）研究是为了在某一特定人群（IGT)，采取某一特定的方法(生活方式干预），证明某种假设（生活方式干预可预防糖尿病的发生）的正确(合理性和可行性）。然后以这种假设去说服人,让人们采取行动解决问题。（大庆）研究是为了改变现状（降低中国乃至世界的糖尿病发病率,当时并未提出代谢综合征）。,三.当前2型糖尿病预防研究的局限及尚未能解决和正在解决的问题,生活方式干预预防糖尿病合理性成本效益?对预防心脑血管病是否有益?可行性多少人能长期坚持?,药物干预预防糖尿病的合理性和可行性最佳剂量？成本效益?耐受性？毒副作用?预防了糖尿病or提前治疗?,UnansweredQuestions,Howtoconductthescreening?Onesteportwo-steps?OGTTorstandardmealtest?Howtodotheprevention?Lifestyleorpharmacological?HOWtotranslatethesesuccessfulfindingsinDa-QingStudyDPPandDPSandmaintainthelifestylechangesinlongertermTargetinginsulinresistanceorinsulininsufficiency?Preventdiabetesorreversetonormaltolerance?Standardprotocolortailoredone?HowToIncreaseEffectivenessandReduceCost?,LifestyleorMedication?,Methodofintervention,DietGroup:BMI25reducecalorieintaketoreduceweight0.5-1.0kg/monthExerciseGroup:Toincreaseamountofleisurephysicalexercisebyatleastoneunit.DietandExerciseGroup:SameasDietandExercisegroupControls:OnlyexposedtogeneralinformationaboutDMfrompublichealtheducation.Nospecialadvice.,Table1.Exerciseunits,Eachcategoryrepresentsoneunit,Lifestyle:HowIntensiveisEffective?,Da-QingStudy:Atleastdecrease50gmofCarbohydrate/dayatleastincrease50minphysicalexercise/day5days/weekDiabetesPreventionProgram:Weightloss7%andexercise150min/weekDiabetesPreventionStudy:Weightloss5%andexercise4hours/week,EfficacyoflifestyleinterventionComparisonofDa-QingStudytoDPPandDPS,Q:ShouldTheChineseNeedtoUseProtocolinDPPorDPSinTheirFuturePrevention?A:Yes?No!Yesorno!Weightloss7%TrailforPreventionDMwithlifestylemodificationinUSTrailforweightlosswithmedication(orlistat)inChineseLifestyleOlistatWeightReduction(Kg)3.006.05WeightReduction(%)3.677.45,过强的生活方式干预会大大增加退出干预的人数，中等强度的干预才能既有效又能为广大人群接受并常年坚持。,DA-QINGSTUDY未采用过于激烈的强度大的干预，失访率仅8%.DPP，DPS体重减轻第一年达标率27?)No,Formostnon-obeseChineseIGT,lessintensivepreventionprotocolthanDPPmaybeworkingifonlyforpreventingDM,howeverreversingthemtonormalglucosetolerancemoreintensivepreventionprotocolisneeded.,PharmacologicalIntervention,Preventionisbetterthancure,糖尿病一级预防研究对象干预措施结果大庆研究IGT生活方式50DPP研究IGT生活方式+双胍58-31%DPS研究IGT生活方式58STOP-NIDDMIGT阿卡波糖33,LifestyleorMedication?,LifestyleinterventionstudieshaveconsistentlyshownthatquitemodestchangescanreducetheprogressionfromIGTtodiabetesby50-60%.Itmay,however,beimpossibletotranslatethesesuccessfulfindingsinlargercohotsormaintainthelifestylechangesinlongerterm.Thishasleadtoconsiderationpharmacotherapy.SimpsonRW,ShawJE,ZimmetPZ:DiabetesResClinPract200359:165-80,改变生活方式的艰难说了,但未听见听见了,但未理解理解了,但未接受接受了,但未付诸行动行动了,但能坚持多久?,Incidence/pysofDMinIGTsubjectstratifiedbyIns-sensitivity,SensitiveIAI-4.73ResistantIAI114,IncidenceofDM,.InIGTsubjectswithhigherdegreesofinsulinresistancethelife-stylechangealoneislesseffectiveinpreventingDMandsomeadditionalinterventionsuchasmetforminmaybeneeded.,DiabetesPreventionProgram(USA),3000IGTinvolved,follow-up3.3years,2001presented,58,31%,STOPNIDDM,1418IGTinvolved,follow-up3years,2001presented,33%,IncidenceofDiabetesinPharmacologicalinterventiongroupofIGTinChina(19972000),77%,88%,0.25tid,50mgtid,IncidenceofDiabetesinPharmacologicalinterventiongroupofIGTinChina(YuexinWang,3years),69%,50mgTID,PharmacologicalinterventionswithAcarboseorMetformincouldreducetheriskofworseningtodiabetesby6080%inChinesesubjectswithIGT.InterventionwithAcarboseseemsmoreeffectiveinChinesethanthatinWesterns,SUMMARY,HowToIncreaseEffectivenessandReduceCost?STRATEGYOFTHEINTERVENTION,Incidence/pysReductionofDMinpeopleswithIGTstratifiedbyINS-SENandsecretion,G4G3G2G1,药物预防的有效性,DPP二甲双呱对年轻肥胖者更有效25-4444%45-5931%6011%BMI22-303%30-3516%3553%,药物预防的有效性,DPP方式干预与二甲双呱疗效比较25-448%45-5941%6069%BMI22-3063%30-3553%35-4%,药物预防的有效性,DPP二甲双呱的有效性PG2H(mg/dl)140-15