糖尿病治療中的餐后血糖控制心內科垂青糖尿病及其并發癥的流行病學特征A1C在糖尿病治療達標中的意義餐后血糖與糖尿病大血管病變餐后血糖與糖尿病微血管病變餐后血糖參與并發癥發生的機制2糖尿病流行情況流行病學進行性增加1985199420002025(百萬)3糖尿病慢性并發癥的患病率*InType2patients;>80%intype1patients.?InType2patients;30%intype1patients.DecisionResourcereportondiabeticcomplications.50%*50%?35%25%4GeissLS,etal.In:DiabetesinAmerica,2nded.1995.Bethesda,MD:NIH;1995.01020304050%ofDeathsIschemicHeartDiseaseOtherHeartDiseaseDiabetesCancerStrokeInfectionOther糖尿病患者死亡原因分布5糖尿病慢性并發癥的經濟負擔ForthecountriesGermany,Belgium,France,Italy,Netherlands,Spain,Sweden,andUKTangLingetal,ChineseHealthEconomics,2003Vol22(12);21-236糖尿病及其并發癥的流行病學特征A1C在糖尿病治療達標中的意義餐后血糖與糖尿病大血管病變餐后血糖與糖尿病微血管病變餐后血糖參與并發癥發生的機制7DCCTResearchGroup.NEnglJMed.1993;329:977-986.OhkuboY,etal.DiabetesResClinPract.1995;28:103-117.UKPDS33:Lancet1998;352,837-853.StrattonIMetal.BMJ.2000;321:405-412.嚴格血糖控制

降低糖尿病并發癥的風險A1cRetinopathyNephropathyNeuropathyCVdiseaseType1DCCT197%63%54%60%41%*Type2Kumamoto297%69%70%-52%*Type2UKPDS387%17-21%24-33%-16%*

*Notstatisticallysignificantduetosmallnumberofevents.

Showedstatisticalsignificanceinsubsequentepidemiologicanalysis48A1C<66-<77-<88-<99-<10>10(%)AdjustedincidenceofmicrovasculardiseaseandMI/1000person-yearsbyupdateA1CconcentrationsinUKPDSStrattonIMetal.BMJ.2000;321:405-412.9StrattonIMetal.BMJ.2000;321:405-412.10ADAACEIDFChinaA1CFasting/preprandialplasmaglucosePostprandialplasmaglucose<7.05.0-7.2<10.0<6.5<6.0<7.8<6.5<6.0NA<6.5<6.1<8.0

AmericanDiabetesAssociation.DiabetesCare2005;28:s1–S36.AmericanAssociationofClinicalEndocrinologists.EndocrinePract2002;8(Suppl.1):40–82.EuropeanDiabetesPolicyGroup.DiabetMed1999;16:716–730.IDFWPR2002,ChineseDiabetesPrevention&TreatmentGuideline血糖控制的臨床目標

11確定血糖達標的關鍵理念A1C是血糖控制的首要目標目標應個體化兒童老人孕婦等人群需特別考慮低血糖好發或嚴重者達標放寬更嚴格的達標(<6.0%)可進一步降低并發癥,但可能增加低血糖危險如餐前血糖達標而A1C未達標,需關注餐后血糖的達標

AmericanDiabetesAssociation.DiabetesCare2005;28:s1–S36.12A1C的重要意義A1C-“金標準”高血糖=A1C升高=并發癥增多A1C是目前反映既往2-3個月血糖控制的最準確的指標13A1C的局限性檢驗方法的差異個體的差異:糖化過程的影響紅細胞代謝速度的影響不能反映血糖的波動:餐后高血糖低血糖A1C代謝動力學的影響:

Day0-30=50%;Day90-120=10%14HbA1c水平與血漿葡萄糖的關系IndiagnosedandundiagnoseddiabetesonlyfromNHANESIII(1988–1994).ADA.ClinicalPracticeRecommendations.DiabetesCare.2004,27:S15-S35.

Mean Mean Mean

HbA1c FPG 2-HourPG HbA1cPlasmaGlucose <6

116/6.4

208/11.6 6135/7.5 6–6.9 132/7.3

233/12.94 7170/9.4 7–7.9

172/9.6

315/17.5 8205/11.4 8–8.9 205/11.4 371/20.6 9240/13.3 >9 278/15.4 432/24 10275/15.315+PostprandialGlucose,Influencedby:PreprandialglucoseGlucoseloadfrommealInsulinsecretionInsulinsensitivityinperipheraltissuesandliverFastingGlucose,Influencedby:HepaticglucoseproductionHepaticsensitivitytoinsulinHbA1c=A1C的組成16A1C與餐后及空腹血糖的相關性StudyDesign66patientswithtype2DMenrolledPatientsweretreatedwithdietalone,dietplusbiguanidesand/orsulfonylureasGlycemicprofileswereobtainedon8:00AM(prebreakfastPG);11:00AM(prelunch);2:00PM(postlunch);5:00PM(extendedpostlunch).AndA1CObjective:toevaluatetherelativevalueofPGatdifferenttimepointsinassessingglucosecontroloftype2DMAvignonA.DiabetesCare20:1822-26,199717AvignonA.DiabetesCare20:1822-26,19975004003002001005004003002001000 4 5 6 7 8 9 10 11 12 5 6 7 8 9 10 11 12 13Pre-breakfastPG

(mg/dL)Post-lunchPG

(mg/dL)Pre-lunchPG

(mg/dL)Extendedpost-lunchPG(mg/dL) y=17.0x+29.1r=0.62 y=37.6x–112.6r=0.81HbA1c(%) y=27.5x–11.3r=0.65 y=30.8x–90.3r=0.78A1C與餐后及空腹血糖的相關性18各點血糖譜與A1C的關系AvignonA.DiabetesCare20:1822-26,199719結論:血糖控制良好時(A1C<7.0%),血糖譜特征是延遲的餐后血糖低于餐前血糖;而血糖控制惡化時延遲的餐后血糖比餐前血糖升高更多與餐前血糖比較,餐后血糖與A1C的相關性更好,因為多元分析顯示只有午餐后及延遲的餐后血糖與A1C值獨立及顯著相關空腹血糖:胰島素敏感性+肝糖輸出餐后血糖:胰島素敏感性+肝糖輸出+內源性胰島素分泌--反映了病理生理過程的更全面的改善AvignonA.DiabetesCare20:1822-26,199720

"...MeanHbA1cisnotthemostcompleteexpressionofthedegreeofhyperglycemia.Otherfeaturesofdiabeticcontrol,whicharenotreflectedbyHbA1cmayaddtoormodifytheriskforcomplications.Forexample,theriskforcomplicationsmaybemorehighlydependentontheextentofpostprandialglycemicexcursions…"

TheDCCTStudyGroup.Diabetes44:968-83,1995餐后高血糖的臨床意義21糖尿病及其并發癥的流行病學特征A1C在糖尿病治療達標中的意義餐后血糖與糖尿病大血管病變餐后血糖與糖尿病微血管病變餐后血糖參與并發癥發生的機制22餐后高血糖與并發癥相關的證據大血管并發癥:DECODEStudyDiabetesInterventionStudyHonoluluHeartProgramChicagoHeartStudyWhiteHallStudyHelsinkiPolicemansStudyNursesHealthStudy23TheDECODEStudy--MortalityandPost-ChallengeGlucoseDatafrom13prospectiveEuropeancohortstudiesIncludedover25,000personswithandwithoutdiabeteswithameanfollowupof7.3yearsEachsubjectevaluatedatbaselinewithafastinganda2-hpost-challenge(75gm)glucoselevelRiskofdeathwasassessedaccordingtoglucosecategoriesThehazardratio(adjustedforageandgender)wasdeterminedforall-causemortalitybyfastingand2-hglucoseclassification.DECODEStudyGroup.Lancet1999;354:617-621.StudyDesign24HazardratioFastingPlasmaGlucose(mM)2-hPlasmaGlucose(mM)012<6.16.1-6.9>7.0<7.87.8-11.0>11.1DECODEStudy:RelativeRiskofMortalityIncreasedwithIncreasing2-HrGlucoseLevelDECODEStudyGroup.Lancet1999;354:617-621.25Conclusions:死亡率增加與糖負荷后2小時血糖顯著相關而與空腹血糖水平無關因此糖負荷后2小時血糖是預測高血糖相關死亡率的最重要指標DECODEStudyGroup.Lancet1999;354:617-621.26TheDiabetesInterventionStudy:PostprandialGlucoseAssociatedwithIncreasedMortalityProspective,population-based,multicentertrialOver1,000patientswithnewlydiagnosedtype2diabetes,ages30to55years.AssessedriskfactorsatbaselineforsubsequentcoronaryheartdiseaseandmortalityInan11-yearfollow-upHanefeldM.Diabetologia1996;39:1577-1583.StudyDesign27<10.0mmol/L>10.0mmol/LPostprandialGlucoseP<0.050100200300Rateper1,000<7.8mmol/L>7.8mmol/LFastingGlucoseP=NSDiabetesInterventionStudy:Postprandial,notFastingGlucose,AssociatedwithIncreasedAll-CauseMortalityMIandMortalityrateper1,000HanefeldM.Diabetologia1996;39:1577-1583.

28Conclusion:2型糖尿病患者死亡率是同年齡總體人群死亡率的5.1-7.0倍多元回歸分析顯示餐后血糖是2型糖尿病患者死亡的獨立危險因素餐后血糖而非空腹血糖是預測2型糖尿病患者發生心梗和死亡的重要指標在糖尿病發病早期嚴格控制餐后血糖對降低大血管并發癥和所有原因導致的死亡率有非常重要的意義HanefeldM.Diabetologia1996;39:1577-1583.29StudyDesign8,006menofJapaneseancestry,ages45to70years.6,394menwithoutDiabetesincludedinanalysisoftherelationshipof1hpostchallengeglucosewithCVDVitalstatusfollowedfor12yearsDonahue,etal.,Diabetes,1987;36:689.HonoluluHeartProgram30Donahue,etal.,Diabetes,1987;36:689.40-114mg/dL115-133mg/dL134-156mg/dL157-189mg/dL190-532mg/dLCasual1-hrSerumGlucose0102030405060FatalCHDFatalCHD+Non-FatalMIRatesper1000p<0.01p<0.001(p-valuescompare5thquintilewith1stquintile)HonoluluHeartProgram:Riskof