餐后高血糖和心血管危險因素

餐后高血糖和心血管危險因素第1頁/共30頁PostPrandialHyperglycemia:

ASignificantCardiovascularRiskFactor&TreatablePrecedentofType2DiabetesDiagnosticCriteriaforType2DMPathophysiologyoftype2DMPostPrandialHyperglycemia(PPH)anddiabeticcomplicationsPreventionofType2DM第2頁/共30頁TheincreasingglobalburdenofdiabetesPopulationaged>20years

KingH,etal.DiabetesCare1998;21:1414–31.DevelopedcountriesDeveloping

countriesWorld

totalPrevalence(%)0246820252000第3頁/共30頁CVDdrivestheeconomicburdenoftype2diabetesCVD:cardiovasculardisease

NicholsGA,BrownJB.DiabetesCare2002;25:482–6.

Copyright?2002AmericanDiabetesAssociation;reprintedwithpermissionfrom

TheAmericanDiabetesAssociation.1086420Costin1999(x1,000US$)NoCVD,

nodiabetesn=13,286NoCVD,

diabetesn=11,130CVD,nodiabetesn=2,894CVDand

diabetesn=5,050$2,562$4,402$6,396$10,17231.9%48.1%20.0%28.6%40.3%31.2%17.2%31.8%51.0%21.1%28.0%50.9%PharmacyOutpatientInpatient第4頁/共30頁Pathophysiologyoftype2diabetesJankaHU.FortschrMed1992;110:637–41.Macro-

vascular

diseaseInsulinsensitivityInsulinsecretionPlasmaglucoseMicro-

vascular

diseaseImpairedglucosetoleranceHyperglycemia第5頁/共30頁Diagnosingglucoseintolerance–

criteriareflectaneedforearlyintervention*Determinedpost75gglucoseload

2h-PG:2-hourpostchallengeplasmaglucose,FPG:fastingplasmaglucose,IFG:impairedfastingglucose,IGT:impairedglucosetolerance

WorldHealthOrganization,1999.Diagnosis Venousplasma

glucoseconcentration

(mmol/L) DiabetesFPGor

>7.02h-PG* >11.1 IGTFPG(ifmeasured)and <7.02h-PG* >7.8and<11.1IFGFPGand

>6.1and<7.02h-PG*(ifmeasured) <7.8第6頁/共30頁FPGand2h-PGvaluesidentify

differentpeoplewithdiabetes2h-PG:2-hourpostchallengeplasmaglucose,FPG:fastingplasmaglucose

DECODEStudyGroup.BMJ1998;317:371–5.FPG

40%BothFPGand

2h-PG

28%Younger,moreobese

peopleOlder,leaner

people2h-PG

32%第7頁/共30頁TheRelativeContributionofFPGandMealtimeGlucoseSpikesto24-hourGlycemicLevelRiddleMC.DiabetesCare1990;13:676–6863002001000Plasmaglucose(mg/dl) 0600 1200 1800 2400 0600Time(hours)Mealtime

glucose

spikesFasting

hyperglycemiaNormal第8頁/共30頁Kuusistoetal,1994GlycemicControlandCHDCHDMortalityAllCHDEvents第9頁/共30頁AComparisonofHba1cLevelsAchievedintheConventionalVersusIntensiveGroupsofMajorTrials1098765 0 1 2 3 4 5 6 7 8 9 10Timefromrandomization(years)HbA1cDCCTKumamotoStudy98760 0 3 6 9 12 15MedianHbA1c(%)Timefromrandomization(years)UKPDSConventionaltherapyIntensivetherapy12111098765 0 12 24 36 48 60 72MonthsHbA1c(%)第10頁/共30頁FPG=fastingplasmaglucose;PPG=postprandialplasmaglucose.HbA1CPPGFPG+=第11頁/共30頁4.85.05.25.45.65.86.06.26.4HbA1c(%)6080100120140160180200Fasting/2hourplasmaglucose(mg/dl)HarrisMIetalDiabetesCare,1998Hba1c,Fastingand2hrPlasmaGlucose第12頁/共30頁UKPDS10yr-CohortData:DissociationBetweenFPG&HbA1CHbA1cFPGDelPratoS.2001PPG第13頁/共30頁DurationofDailyMetabolicConditionsBFLunchDinner0:00am4:00amBFPostprandialPostabsorptiveFastingMonnierL,EuropJClinInvest,2000第14頁/共30頁IntensiveTreatmentPolicies

DCCT

KumamotoStudy

UKPDS

Fastingplasmaglucose(mmol/l)

3.9–6.7

<7.8

<6

2-hrppglucose(mmol/l)

<10

<11

Notdefined

第15頁/共30頁TheFunagataCohortPopulation

**********TominagaMetal.DiabetesCare,1999NGT

-

IFG

-

DMAllcausesofdeath0.8600.8800.9000.9200.9400.9600.9801.00001234567Years第16頁/共30頁TheFunagataCohortPopulation

**********TominagaMetal.DiabetesCare,1999*****NGT

-

IGT

-

DM第17頁/共30頁Summary1.Type2DMbeginsasapostprandialdisease2.PostprandialhyperglycemiacontributestoelevationsinHbA1candcomplications3.Treatmentofpostprandialhyperglycemiaiscriticaltoachievingoptimaloutcomesintype2DM4.Nevertheless,treatmentofpostprandialhyperglycemiaisinadequatelyaddressed第18頁/共30頁STOP-NIDDMStudytoPreventNon-insulin

DependentDiabetesMellitusSTOPNIDDM第19頁/共30頁StudydesignSTOPNIDDMPlacebot.i.d.(n=715)Acarbose100mgt.i.d.(n=714)–1036612182430Months1234567891011121314VisitsPlacebo

n=1,4293monthsplacebo60Close-outvisitt.i.d.:threetimesdaily

ChiassonJL,etal.Lancet2002;359:2072–7.第20頁/共30頁Acarbosereducestherisk

ofdevelopingdiabetesSTOPNIDDMAcarbosereducestheincidenceoftype2diabetesinindividualswithIGTBasedononepositiveOGTT25%p=0.0015Basedontwo

consecutivepositiveOGTTs36%p=0.0017IGT:impairedglucosetolerance,OGTT:oralglucosetolerancetest

ChiassonJL,etal.Diabetologia2002;45(Suppl.2):A104.第21頁/共30頁AcarbosehasarapidandsustainedeffectondiabetesriskAcarbose-associatedreductioninriskofdiabeteswasevidentafter1yearAcarbosesignificantlyreducedtheriskofdiabetesateachfollow-uptimepointThebeneficialeffectsofacarbosepersistedforthedurationofthetrialResultsoftheSTOP-NIDDMshowthatacarbosehaslong-termtherapeuticefficacyinindividualswithIGTIGT:impairedglucoseintolerance,STOP-NIDDM:StudytoPreventNon-insulin

DependentDiabetesMellitus

ChiassonJL,etal,Lancet2002;359:2072–7.STOPNIDDM第22頁/共30頁EfficacyofacarboseisunaffectedbybaselineBMIorageSTOPNIDDMBMI:bodymassindex

ChiassonJL,etal.Lancet2002;359:2072–7.p25%0.001521%0.055931%0.008423%0.038229%0.008924%0.026930%0.011500.51.01.52.0FavoursacarboseOverallAge(years)

<55>55SexMaleFemaleBMI(kg/m2)

>30<30FavoursplaceboReductioninincidence

第23頁/共30頁Acarboseincreasesthe

reversionofIGTtoNGTNGTIGTDiabetesAtbaselineAcarbosegroup(%)Placebogroup(%)324228253531Atendoftreatment100%***Nopost-randomisationdata

IGT:impairedglucosetolerance,NGT:normalglucosetolerance

ChiassonJL,etal.Lancet2002;359:2072–7.STOPNIDDM第24頁/共30頁Acarbose–anexceptionalsafetyprofile*Eventsstartingonthefirstdayandupto7daysafterlastdayoftreatmentBayerAG,dataonfile2002.Adverseevents 155 (21.7) 277 160 (22.4) 260

experienced Bodyasawhole 56 (7.8) 77 58 (8.1) 72Cardiovascular 33 (4.6) 48 39 (5.5) 61Endocrine 4 (0.6) 5 5 (0.7) 5Haemic 2 (0.3) 2 4 (0.6) 4

andlymphaticMetabolicand 2 (0.3) 2 1 (0.1) 1

nutritional Adverseevents* Acarbose(n=714)PatientsEvents

No.(%)No.Placebo(n=715)PatientsEvents

No.(%)No.STOPNIDDM第25頁/共30頁AcarbosereducestheriskofcardiovasculardiseaseSTOPNIDDM*Reductioninriskofdevelopinghypertension

DatawereanalysedusingtheCoxproportionalhazardmodel

ChiassonJL,etal.Diabetologia2002;45(Suppl.2):A104.Hypertension*Myocardial

infarctionAnycardio-

vasculareventp=0.0059p=0.0226p=0.032634%91%49%第26頁/共30頁ReducingpostprandialhyperglycaemiadecreasestheriskofdiabetesandCVDSTOPNIDDMAcarbosetreatmentresultedinaRelativeriskreductionof25%forthedevelopmentofdiabetes(p=0.0015)1Relativeriskreductionof36%usingtwoconsecutiveOGTTs(p=0.0017)130%increaseintheincidenceofnormalglucosetolerance(p<0.0001)2StatisticallysignificantreductionintheriskofhypertensionmyocardialinfarctionanycardiovasculareventCVD:cardiovasculardisease,OGTT:oralglucosetolerancetest

1.ChiassonJL,etal.Diabetologia2002;45(Suppl.2):A104.

2.BayerAG,dataonfile2002.第27頁/