小时糖耐量试验的临床意义

2小时糖耐量试验的临床意义

FinnishAcademyResearchFellow芬兰赫尔辛基大学及国立公共卫生研究院 北大糖尿病论坛2007年5月12日，北京乔青MD,Ph.D

糖尿病诊断试验:历史回顾糖尿病症状尿糖空腹血糖糖耐量(1913年)

JacobsenA.BiochemZ51:443,1913NormalGlucoseHomeostasis

DaytimeProfile(N=12,health;Mean+95%CI)OwensD,ZinmanB&BolliG:Lancet358,739,2001MealTimes80400Insulin(mU/L)08.0013.0016.0019.00hGlucose(mmol/L)8426什么是糖耐量异常?1.高于均值+2标准差可诊断糖尿病:

根据年轻(20-30岁)健康人群资料,纯统计！不考虑临床，预后及年龄 (50年代)

2h全血血糖>=120mg/dl(100g糖耐量)诊断糖尿病(血浆血糖比全血高14-16%!)发病率高诊断标准混乱(血样，服糖量，时间)直到70年代MosenthalH.O.andBarryE(AnnInternMed33:1175,1950)什么是糖耐量异常?1.均值+2标准差2.血糖双峰分布,小血管病变(眼病，肾病等):糖尿病高发人群,如PimaIndians(1971),Mexican-Americans,Micronesians,PolynesiansBimodaldistributionofglucose

andprevalenceofretinopathyandproteinuriainPimaIndiansKnowlerWCetc.DiabetesMetabRev6:1-27,1990Copyright©1994BMJPublishingGroupLtd.McCane,DRetal.BMJ1994;308:1323-85yearcumulativeincidence(top)andprevalence(bottom)ofretinopathyinrelationtotenthsof2hPG,FPG,andHBa1c现用诊断标准NDDG1979:FPG>=7.8mmol/land75gOGTTat½,1,1½,2hours

WHO1980:adoptedtheNDDGcriteria,2hglucose>=11.1mmol/lafter75gloadas“金标准”WHO1985:slightlymodifiedtheWHO1980criteriaADA1997:FPG7.8mmol/lto7.0mmol/l，NotuseOGTTWHO1999:adoptedtheFPG7.0mmol/l,retainedthe2hOGTTWHO/IDF2006:nochangesexceptforsometerms什么是糖耐量异常?1.均值+2标准差2.血糖双峰分布,小血管病变3.大血管病变:心脑血管及外周血管病变Dysglycemia>>NormoglycemiainAcuteandStableCVDiseaseConsecutivepts:2107in-pts;2854out-ptelectiveCVconsultsinEurope(71%men;meanage66)OGTT/oldDMin1587(75%)acute&1857(66%)electiveptsbeforedischargeorwithin2mo.EuroHeartSurveyBartnikMetal;EurHtJ2004;1880NGTIFGIGTKnownDMNewDM29%35%22%22%31%30%15%10%3%3%020406080100%AcuteElectiveThe

DECODEStudy(http://www.ktl.fi/decode/index.html)DiabetesEpidemiology:CollaborativeanalysisOfDiagnosticcriteriainEurope2-hourplasmaglucose(mmol/l)<7.87.8–11.0³11.1Total<6.16.1–6.921,9682,0202,56289331620624,8463,119³7.02763784891,143Fastingplasmaglucose(mmol/l)Total24,2643,8331,01129,108AdaptedfromDECODEStudyGroup.BrMedJ1998;317:371–375Classificationofindividuals-theDECODEStudyDiscrepancyofFPGand2hPGcriteriaintheDECODAstudyDiabetologia2000;43:1470-147530-3940-4950-5960-6970-7980-89Prevalence(%)ofnewlydiagnosedDMinDECODEpopulationsTheDECODEgroup,DiabetesCare2003;26:61-69.30-3940-4950-5960-6970-7980-89Prevalence(%)ofIGTbutnotIFGincreaseswithageinDECODEpopulationTheDECODEgroup,DiabetesCare2003;26:61-69.Hazardsratioforall-causemortalityinsubjectswithoutpriorhistoryofdiabetesAdj.forage,cohorts,sex,chol,BMI,SBP,smoking2-hourplasmaglucose

(mmol/l)

³7.0 6.1–6.9 <6.1 ³11.17.8–11.0<7.8Fastingplasmaglucose(mmol/l)2.52.01.51.00.50.0HazardratioAdaptedfromDECODEStudyGroup,Lancet1999;354:617–621All-causemortalityhasalinearrelationshipwith2-hourplasmaglucoseDECODE,DiabetesCare2003;26:688-696CVDmortalityby2-hourplasmaglucoseFrequencyHazardratioDECODE,DiabetesCare26:688-696CVDmortalitybyfastingplasmaglucoseFrequencyHazardratioDECODE,DiabetesCare26:688-696HazardratioformortalitybyFPGcategories,theDECODAStudyFPG(mmol/l)<6.1(n=5547)6.1-6.9(n=462)7.0(n=297)PfortrendCVDModel1Model2111.4(0.9-2.1)1.1(0.7-1.7)2.0(1.3-3.1)0.9(0.5-1.5)0.0060.83All-causeModel1Model2111.2(0.9-1.6)0.9(0.7-1.3)1.8(1.3-2.5)0.9(0.6-1.3)0.0010.81Model1:Adjustedforage,sex,cohort,BMI,sysBP,CholandsmokingModel2:Additionaladjustmentfor2hPGDECODAStudyGroup,Diabetologia2004;47:385-394Hazardratioformortalityby2hPGcategories,theDECODAStudy2hPG(mmol/l)<7.8(n=4753)7.8-11.0(n=1106)11.1(n=447)PfortrendCVDModel1Model2111.3(0.9-1.9)1.3(0.9-1.9)3.2(2.2-4.7)3.4(2.1-5.4)<0.001<0.001All-causeModel1Model2111.3(1.0-1.7)1.4(1.0-1.8)2.9(2.2-3.8)3.0(2.2-4.2)<0.001<0.001Model1:Adjustedforage,sex,cohort,BMI,sysBP,CholandsmokingModel2:AdditionaladjustmentforFPGDECODAStudyGroup,Diabetologia2004;47:385-394Non-diabeticDiabeticFollow-upBaseline2hPGNGTIGTNon-diabeticCHDincidence5.39.716.1CVDmortality3.17.98.7All-causemortality7.612.815.5Incidencedensity(no./per1000person-years)Qiaoetal.DiabetesCare2003;26:2910-2914Hazardratio(95%CI)byglucosestatusatbaselineandatfollow-upFollow-upNon-diabeticDiabeticBaseline2hPGNGTIGTNon-diabeticCHDincidence11.5(1.0-2.3)1.8(1.0-3.2)CVDmortality12.3(1.4-3.9)1.7(0.8-3.5)All-causemortality11.7(1.1-2.4)1.5(0.9-2.5)Adjustedforage,sex,WHR,SBP,Chol,HDLandsmokingQiaoetal.DiabetesCare2003;26:2910-2914EffectofintensiveglycemiccontrolontheriskforanytypeofmacrovasculareventsCStettler,AmHeartJ2006;152:27-38STOP-NIDDMTrial(1)MyocardialinfarctionAnginaRevascularizationprocedureCardiovasculardeathCerebrovasculareventorstrokePeripheralvasculardiseaseAnycardiovasculareventFavoursAcarboseFavoursPlaceboChiassonJLJAMA2003;23:290:486-94Themainchangesfrombaselineto3years:

Acarbose PlaceboSTOP-NIDDMTrial(3)BodyWeight(kg) -1.15 0.26 BMI(kg/m2) -0.60 -0.12Waist(cm) -0.62 0.17SysBP(mmHg) -0.97 -0.05DiasBP(mmHg) -2.8 -1.42hPG(mmol/L) -0.63 0.04Triglycerides(mmol/L) -0.18 -0.04 Allp<0.01forthedifferencebetweenthetwogroupsSummaryDiabetesdiagnosedbyeitherFPGor2hcriteriaareriskfactorforCVDdisease,but2hcriteriaidentifythosewhoarenotdiabeticbyFPGaloneIGTisoverIFGwithregardtothepredictionoftheCVDMoretrialsarerequiredtoshowthatintensivetreatmentofpostprandialhyperglycemiacanreducetheCVDRCTMeta-analysis:GLoweringType1DiabetesTrialsAmHeartJ2006;152:27IntensiveInsulinRx&CVD:T1DM

DCCT/EDICNEJM2005;353:2643Participants:1394(97%oftheoriginalcohort) DCCTparticipantsOutcome: NonfatalMIorstroke;ORCVdeath; ORsilentMI;ORdocumentedangina; ORrevascularizationFollow-up:Until>50conventionalpts-CVevent 11yrspostDCCT;17yrsaltogetherGHbResults:DCCTEndEDICEndIntensive7.4(1.1)7.9(1.3)Conventional9.1(1.5)7.8(1.3)IntensiveInsulinRx&CVD:T1DM

DCCT/EDICNEJM2005;353:2643PrimaryCVCompositeRRR=42%(9-63)RRRafteradj.forupdatedGHbuntilendofDCCT(orCVeventduringDCCT):16%(-64–57)P=0.61IntensiveInsulinRx&CVD:T1DM

DCCT/EDICNEJM2005;353:2643MI,Stroke,CVDeathRRR=57%(12-79)ChronicGLowering&CVD:IGT

STOPNIDDMAnalysis:Chiassonetal.JAMA2003;290:486HR0.51(0.28-0.95)(i.e.32/686vs.15/682MI,Angina,Revasc,CVDeath,CHF,Stroke,orPVD)Copyright©1994BMJPublishingGroupLtd.McCane,DRetal.BMJ1994;308:1323-8ROCcurvesforprevalenceofretinopathy(top)andnephropathy(bottom)for2hPG(----),FPG(....),andHbA1(----)concentrations1-SpecificityRelativerisk(95%CI)ofmortality

significantlyincreasedinsubjectswithIGTMultivariateadjusted:forage,center,sex,cholesterol,BMI,BP,smokingMortalityRR,multivariateadjustedRR,adjustedalsoforFPGCVD1.34(1.14-1.57)1.32(1.12-1.56)CHD1.28(1.02-1.59)1.27(1.03-1.58)Stroke1.26(0.88-1.80)1.21(0.84-1.74)All-cause1.40(1.27-1.54)1.37(1.25-1.51)TheDECODEgroup,ArchInternMed2001;161:397-404HazardsratioformortalityindiabeticpatientsaccordingtoFPGTheDECODEgroup,ArchInternMed2001;161:397-404Adjustedforage,center,sex,cholesterol,BMI,BP,smoking

Hazardsratioformortalityindiabeticpatientsaccordingto2-hourglucoseTheDECODEgroup,ArchInternMed2001;161:397-404Adjustedforage,center,sex,cholesterol,BMI,BP,smoking

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