PregnancycomplicatedwithDiabetesDiabetesinPregnancyPre-gestationalDiabetes:

Type1DM+Type2DM10%~20%GestationalDiabetesMellitus(GDM):>80%

GDMDiettherapyGDMDiet+Insulin

After1921(insulindiscovery)Insulintreatmentfordiabetesbegan,andmaternalandfetaloutcomeimprovedsignificantly.Now,thePNMofpregnantwomenwithDMissimilartonormalpregnantwomen.But,perinatalmorbidityisstillhigh.Fig1.PerinatalMortalityrateindiabeticpregnancy(1890-1981)EffectsofPregnancyuponGlucoseMetabolismPlacentalhormones&cytokines

Humanplacentallactogen(HPL)Estrogen&ProgesteroneTNF,Leptin

InsulinaseGeneticfactors

InsulinResistance(IR)GestationalDiabetesMellitusGDMisdefinedasanydegreeofglucoseintolerancewithonset

duringpregnancy.

Excludedthepossibilitythatunrecognizedglucoseintolerancemayhaveantedatedorbegunconcomitantlywiththepregnancy.Withmeticulousmetabolicandobstetricmanagement,itispossibleforGDMpatientstovaginallydeliveranormalinfant.Guideline:Diagnosticcriteriaforgestationaldiabetesmellitus(WS331-2011)ChinMedJ2012;125(7):1212-1213HighriskfactorsofGDM

Age≥30yearsoldObesityand/orPCOSRapidlyweightgainduringpregnancyFamilyhistorywithdiabetesPoorobstetrichistoryhistoryofGDM,historyofNRDS,fetaldefects,macrosomia,polyhydramniosHansonMA,etal:Earlylifeopportunitiesforpreventionofdiabetesinlowandmiddleincomecountries.BMCpublichealth2012;12:1025.

孕期環(huán)境暴露影響子代慢性疾病發(fā)病風險GDM診斷界值？HAPO研究

（HyperglycemiaandAdversePregnancy）HAPO研究始于2000年7月，北美洲、歐洲、中東、亞洲和澳洲的9個國家15個研究中心參與，23316名符合入組條件的孕婦進行雙盲的前瞻性研究.收集入組孕婦的背景數(shù)據(jù)和臨床檢驗數(shù)據(jù)、分娩結局。研究中僅僅對空腹血糖（fastingplasmaglucose,FPG）>5.8mmol/L或服糖后2小時血糖>11.1mmol/L或隨機血糖>8.9mmol/L者進行血糖管理和干預。HAPO研究將75gOGTT三項中各點血糖值分別分為7級，研究結果發(fā)現(xiàn)，隨OGTT各點血糖值級別增加，LGA、剖宮產(chǎn)率（首次）、新生兒低血糖及臍血C肽不良妊娠結局的發(fā)生率均明顯增加。HAPO結果進行分析，發(fā)現(xiàn)OGTT三項血糖值對結局的影響并無明確拐點，GDM診斷界值：OGTT空腹5.1mmol/L，1小時10.0mmol/L2小時8.5mmol/L（1.75倍OR）DiagnosisofGDMGDMisdiagnosedby75gOGTT@24-28GWsGDMcanbediagnosedbyanyoneabnormalvaluesof75gOGTT(5.1,10.0,8.5mmol/L)

WHOcriteriafordiagnosisandclassificationofhyperglycaemiafirstdetectedduringpregnancy

（WHO,2013）早孕期篩查診斷出孕前漏診的糖尿病（overtdiabetes）PrevalenceofGDMinChina19951996199719981999200020012002200320042005—2009年GDM患病率14.6％2011-2012年17.5%

孫偉杰，楊慧霞.中華婦產(chǎn)科雜志，2007魏玉梅，楊慧霞.中華婦產(chǎn)科雜志，2011ZhuWW,YangHX,etal.DiabetesCare,2013Birthweight/neonataladiposityFetalhyperinsulinemiaType2diabetesCesareansectiondeliveryShoulderdystocia/birthinjuryPreeclampsiaGDMduringnextpregnancyType2diabetesObesityCardiovasculardiseaseWhywebothertoscreenGDM?

Long-termandshort-termeffectsbothformothers&offspringNeonatalhypoglycemiaCongenitalmalformationIncidenceofType2DiabetesMellitus

AfterPregnancyComplicatedbyGDMJ.B.O’Sullivan,BodyWeightandSubsequentDiabetesMellitus,JAMA1982;248(8):949-52Type2diabetesNeonatallifePregnanciesMiddleageNormalglucosetoleranceInsulinresistanceLifespanGDMGDMPregnancyasastresstestforfuturemetabolicsyndromeInsulinresistance

EffectofGDMontheFetus

PlacentaMATERNALFETALINSULINRELEASEGLUCOSEUTILIZATIONHYPERGLYCEMIABIRTHWEIGHTHYPERINSULINEMIAHYPERGLYCEMIAEmbryo-----FetusDeliveryPeriodOfexposure1sttrimester2ndtrimester3rdtrimesterorganogenesisSpontanetousabortionsEarlygrowthdelayCongenitalanomaliesMacrosomiaOrganomegalyCNSdevelopmentdelayChronichypoxemiaStillbirthBirthinjuryAdultObesity↓Impairedglucosetolerance↓Diabetessyndrome-XBehaviorintellectdeficitFetalmalformationandHbA1cRoyTaylor.etal.BMJ.2007;334:742-745

Anoffspringofadiabeticmotherdeliveredat38weeksgestationbeinglarge,oedematousandplethora

MaternalDeterminantsofObesity&DMOBdoctorsfirsttoidentify&intervenetoreduceobesityandtype2DMExposuretoadiabeticenvironmentinuteroisassociatedwithincreasedoccurenceofIGTinadultoffspring,independentofgeneticpredispositiontotype2DM

DiabetesinWomen.3rded.Philadelphia，PA：LippincottWilliams&Wilkins；2004Barker1989MaternalUnder-nutritionMaternalOver-nutrition&hyperglycemiaMSType2DMHypertensionBarker,etal.1992，1995，1999Obesity&Type2DMNapoli，1997，1999Campbel,1996Shiell，2000Cerf,2005Whitaker，1998Buckley，2005Mulhausle,2006TheoffspringborntothemotherwithGDMhavegreaterlikelihoodofdevelopingobesity&diabetes11歲時的代謝綜合征BoneyCM,etal.Pediatrics.2005;115:e290-6.

GDM組大于胎齡兒GDM組適于胎齡兒非GDM組大于胎齡兒非GDM組適于胎齡兒患病率15%患病率5.3%該地區(qū)一般人群MS普遍患病率為4.8%患病率3.0%患病率4.2%AviciouscircleHossainetal:

ObesityandDiabetesintheDevelopingWorld–AGrowingChallenge.NEJM356(2007)213-215.

媽媽，快點讓我處在正常血糖中吧ManagementofGestationalDiabetesDietSeIfglucosemonitoringOralhypoglycemicsInsulinadministrationEducationaboutdiabetesDietCaveatsDietarycomplianceiskeytosuccessfulmanagementofGDM.Dietsrestrictedincaloriespredisposetoketosis.Carbohydraterestricteddietsmayimprovecontrolandreducecomplications.SeIfglucosemonitoringBloodGlucoseMonitoringBloodglucosetest:(pre-meal,2hpost-meal,0a.m.orbedtime)CapillaryglucosechemicalteststripsasthestandardofcareforpregnancymonitoringGlycohemoglobin(HbA1c)Glucosuriaismorelikelytooccur(lowerrenalthreshold)SeIfglucosemonitoringThetargetglucoselevelsFBG&Pre-meal<5.3mol/L(95mg/dl)Post-meal2h<6.7mmol/L(120mg/dl)Post-meal1h<7.8mmol/L(140mg/dl)

AvoidnocturnalhypoglycemiaandketosisOralhypoglycaemicagentsMetforminWillcontrolBSLin~50-60%BUTcrossesplacentaandcautionuntillong-termfollow-upstudiesGlyburideStudiesnotpoweredtodeterminefetal/neonataloutcomesStimulatesβ-isltcells(alreadystressed)Againlong-termstudiesrequiredforbothneonateandmother.二甲雙呱應用組圍產(chǎn)結局與insulin組無差別，孕婦接受性好，但遠期安全性有待證實。妊娠期口服降糖藥臨床應用胰島素增敏劑:二甲雙胍

FDAB類藥物孕前和妊娠早期應用二代磺脲類降糖藥:(Glubride,格列苯脲)幾乎不透過胎盤孕13周以后應用

Pre-existingDM

Manypregnanciesunplanned ManywomenwithdiabetesnotdiagnosedEnsureoptimalbloodglucosecontrolInvestigateandtreatanyassociatedhypertension,renalorretinaldisease糖尿病合并妊娠圍產(chǎn)兒死亡率圍產(chǎn)兒死亡率（%）作者國家患者1型糖尿病2型糖尿病背景人群Coetzee1985南非8477.73.7?(31.3)?3.1Sacks1997美國15903.5Gunton2000澳大利亞8509.10.8Cundy2000新西蘭5941.34.61.3Dunne2003英國1632.51.0DPG2003法國4356.64.10.7Hadden2003英國1612.50.9-2.1Clausen2005丹麥3011.76.70.8McElduff2005澳大利亞1801.25.10.7CheungNW,etal.AustralianandNewZealandJournalofObstetricsandGynaecology.2005;45:479-483?妊娠期間接受治療?妊娠期間沒有接受治療糖尿病合并妊娠和胎兒嚴重先天畸形發(fā)生率嚴重先天畸形發(fā)生率（%）作者國家患者1型糖尿病2型糖尿病背景人群Omori1994日本20705.8Towner1995美國33211.72Sacks1997美國159714Gunton2000澳大利亞6422.29.1Schaefer-Graf2000美國4168.9Brydon2000英國2536.112.2Farrel2002新西蘭7757.24.5Dunne2003英國1829.90.9DPG2003法國4354.53.42.2Clausen2005丹麥3012.96.72.9McElduff2005澳大利亞1806101.1-2.1CheungNW,etal.AustralianandNewZealandJournalofObstetricsandGynaecology.2005;45:479-483糖尿病者妊娠前血糖控制目標目標血漿（mmol/L）全血mmol/L空腹和餐前血糖4.4-6.13.9-5.6餐后2h血糖5.6-8.65.0-7.8HbA1c＜7%，盡可能降到正常避免低血糖Firsttrimester(pre-existingdiabetes)Tightcontrolofbloodglucoselevels

CongenitalmalformationOphthalmologyconsult

Insulinsecretionishigheraftermeals24hourclockTopline,pregnancyLowerline,non-pregnantInsulinuU/mlPregnancy(topline)Non-pregnant(lowerline)孫偉杰，楊慧霞等（2005）中華圍產(chǎn)醫(yī)學雜志PrenatalObstetricManagementPrenataldiagnosisAssessingfetalgrowthPeriodicfetalmonitoringfrom32GWs(NST、AFI)PlanTimingandRouteofDeliveryConfirmationoffetalmaturityDELIVERYOFDIABETICPATIENTSWithwell-controlledbloodglucose,thetimeofdeliveryisbeforetheestimatedduedateGDMA1:40GWsGDMA2/Pre-GDM:38-39GWsAmniocentesisonlyforuncontrolledGDMorearlydelivery(<37GWs)Delivery&PostpartumRiskofdystociaRiskofshoulderdystociaReducedinsulinrequirementpostpartumLong-termcounselingPre-gestationalDiabetesMellitus(Summary)ProvidepreconceptioncareOptimizeglucoseandavoidhypoglycemia.Evaluatefetaldevelopmentandgrowth.Managerenal,eye,orotherendorgandamage.Assessmotherforcomplicationsandfetusforwell-being.Encouragebreast-feeding,contraceptionandpreconceptioncare.NeonatalmonitoringAvoidneonatalhypoglycemia:earlyfeedingExamineforcongenitalmalformationsNRDSPolycytemiaBirthtrauma鼓勵母乳喂養(yǎng)/

PostpartumManagementofGDMFBGismeasuredbeforedischarge75g2-hrOGTTisr