1、Pregnancy complicated with DiabetesPeking University First Hospital Huixia YangvPre-gestational Diabetes:Type1 DM+Type2 DM 10%20%vGestational Diabetes Mellitus(GDM):80%GDM Diet therapy GDM Diet+Insulin vInsulin treatment for diabetes began,and maternal and fetal outcome improved significantly.vNow,t
2、he PNM of pregnant women with DM is similar to normal pregnant women.vBut,perinatal morbidity is still high.Fig 1.Perinatal Mortality rate in diabetic pregnancy(1890-1981)Effects of Pregnancy upon Glucose Metabolism vPlacental hormones&cytokines Human placental lactogen(HPL)Estrogen&Progesterone TNF
3、 ,Leptin vInsulinasevGenetic factors Insulin Resistance(IR)Gestational Diabetes MellitusvGDM is defined as any degree of glucose intolerance with onset during pregnancy.vExcluded the possibility that unrecognized glucose intolerance may have antedated or begun concomitantly with the pregnancy.vWith
4、meticulous metabolic and obstetric management,it is possible for GDM patients to vaginally deliver a normal infant.Guideline:Diagnostic criteria for gestational diabetes mellitus(WS 331-2011)Chin Med J 2012;125(7):1212-1213 High risk factors of GDMv Age 30 years old v Obesity and/or PCOSv Rapidly we
5、ight gain during pregnancyv Family history with diabetesv Poor obstetric history history of GDM,history of NRDS,fetal defects,macrosomia,polyhydramniosHanson MA,et al:Early life opportunities for prevention of diabetes in low and middle income countries.BMC public health 2012;12:1025.孕期环境暴露影响子代慢性疾病发
6、病风险孕期环境暴露影响子代慢性疾病发病风险GDM 诊诊断界值？断界值？HAPO研究研究（Hyperglycemia and Adverse Pregnancy）vHAPO研究始于研究始于2000年年7月，北美洲、欧月，北美洲、欧洲、中东、亚洲和澳洲的洲、中东、亚洲和澳洲的9个国家个国家15个研究个研究中心参与，中心参与，23316名符合入组条件的孕妇进名符合入组条件的孕妇进行行双盲的前瞻性研究双盲的前瞻性研究.v收集入组孕妇的背景数据和临床检验数据、收集入组孕妇的背景数据和临床检验数据、分娩结局。研究中仅仅对空腹血糖分娩结局。研究中仅仅对空腹血糖（fasting plasma glucose,
7、FPG）5.8mmol/L或服糖后或服糖后2小时血糖小时血糖11.1mmol/L或随机血糖或随机血糖8.9mmol/L者进行血糖管理和干预。者进行血糖管理和干预。vHAPO研究将研究将75gOGTT三项三项中各点血糖值中各点血糖值分别分为分别分为7级，研究结果发现，随级，研究结果发现，随OGTT各各点血糖值级别增加，点血糖值级别增加，LGA、剖宫产率剖宫产率（首（首次）、次）、新生儿低血糖新生儿低血糖及及脐血脐血C肽肽不良妊娠结不良妊娠结局的发生率均明显增加。局的发生率均明显增加。HAPO结果进行分析，发现结果进行分析，发现OGTT三三项血糖值对结局的影响并无明确拐点，项血糖值对结局的影响并无
8、明确拐点，GDM诊断界值：诊断界值：OGTT空腹空腹5.1mmol/L，1小时小时10.0mmol/L2小时小时8.5mmol/L（1.75倍倍OR）vGDM is diagnosed by 75g OGTT 24-28 GWsvGDM can be diagnosed by any one abnormal values of 75g OGTT(5.1,10.0,8.5mmol/L)WHO criteria for diagnosis and classification of hyperglycaemia first detected during pregnancy （WHO,2013）
9、早孕期筛查诊断出孕前漏诊的糖尿病（早孕期筛查诊断出孕前漏诊的糖尿病（overt diabetes）Prevalence of GDM in China1995 1996 1997 1998 1999 2000 2001 2002 2003 200420052009年年GDM患病率患病率 14.62011-2012年年 17.5%孙伟杰，杨慧霞孙伟杰，杨慧霞.中华妇产科杂志，中华妇产科杂志，2007魏玉梅，杨慧霞魏玉梅，杨慧霞.中华妇产科杂志，中华妇产科杂志，2011Zhu WW,Yang HX,et al.Diabetes Care,2013Birth weight/neonatal adip
10、osityFetal hyperinsulinemiaType 2 diabetesCesarean section deliveryShoulder dystocia/birth injuryPreeclampsiaGDM during next pregnancyType 2 diabetesObesityCardiovascular diseaseWhy we bother to screen GDM?Long-term and short-term effects both for mothers&offspringNeonatal hypoglycemiaCongenitalmalf
11、ormationIncidence of Type 2 Diabetes MellitusAfter Pregnancy Complicated by GDMJ.B.OSullivan,Body Weight and Subsequent Diabetes Mellitus,JAMA 1982;248(8):949-52Type 2 diabetesNeonatal lifePregnanciesMiddle ageNormal glucose toleranceInsulin resistanceLife spanGDMGDMPregnancy as a stress test for fu
12、ture metabolic syndromeInsulin resistance Effect of GDM on the Fetus PlacentaMATERNALFETALINSULIN RELEASEGLUCOSE UTILIZATIONHYPERGLYCEMIABIRTHWEIGHTHYPERINSULINEMIAHYPERGLYCEMIAE Em mb br ry yo o-F Fe et tu us sDeliveryDeliveryPeriodPeriodOf exposure Of exposure 1st trimester1st trimester2nd trimest
13、er2nd trimester3rd trimester3rd trimesterorganogenesisorganogenesisSpontanetous abortions Spontanetous abortions Early growth delayEarly growth delayCongenital anomaliesCongenital anomaliesMacrosomiaOrganomegalyCNS development delayChronic hypoxemiaStill birthBirth injuryBirth injuryA Ad du ul lt tO
14、besityImpaired glucose toleranceDiabetes syndrome-XBehavior intellect deficitRoy Taylor.et al.BMJ.2007;334:742-745 An offspring of a diabetic mother delivered at 38 weeks gestation being large,oedematous and plethora Maternal Determinants of Obesity&DMOB doctors first to identify&intervene to reduce
15、 obesity and type2 DMExposure to a diabetic Exposure to a diabetic environment in environment in uteroutero is is associated with associated with increased increased occurenceoccurence of of IGT in adult offspring,IGT in adult offspring,independent of genetic independent of genetic predisposition to
16、 type 2 predisposition to type 2 DMDM Diabetes in Women.3rd ed.Philadelphia，PA：Lippincott Williams&Wilkins；2004 The offspring born to the mother with GDM have greater likelihood of developing obesity&diabetes 11岁时的代谢综合征岁时的代谢综合征Boney CM,et al.Pediatrics.2005;115:e290-6.GDM组组大于胎龄儿大于胎龄儿GDM组组适于胎龄儿适于胎龄儿非
17、非GDM组组大于胎龄儿大于胎龄儿非非GDM组组适于胎龄儿适于胎龄儿患病率患病率15%患病率患病率5.3%该地区一般人群该地区一般人群MS普遍患病率为普遍患病率为4.8%患病率患病率3.0%患病率患病率4.2%A vicious circleHossain et al:Obesity and Diabetes in the Developing World A Growing Challenge.NEJM 356(2007)213-215.妈妈，妈妈，快点让我处在快点让我处在正常血糖中吧正常血糖中吧Management of Gestational DiabetesvDietvSeIf gluc
18、ose monitoringvOral hypoglycemicsvInsulin administrationvEducation about diabetesvDietary compliance is key to successful management of GDM.vDiets restricted in calories predispose to ketosis.vCarbohydrate restricted diets may improve control and reduce complications.vBlood Glucose MonitoringvBlood
19、glucose test:(pre-meal,2h post-meal,0 a.m.or bedtime)Capillary glucose chemical test strips as the standard of care for pregnancy monitoring vGlycohemoglobin(HbA1c)Glucosuria is more likely to occur(lower renal threshold)vThe target glucose levelsvFBG&Pre-meal 5.3mol/L (95mg/dl)vPost-meal 2h 6.7mmol
20、/L (120mg/dl)vPost-meal 1h 7.8mmol/L (140mg/dl)Avoid nocturnal hypoglycemia and ketosisOral hypoglycaemic agentsvMetformin Will control BSL in 50-60%BUT crosses placenta and caution until long-term follow-up studiesvGlyburide Studies not powered to determine fetal/neonatal outcomes Stimulates-islt c
21、ells(already stressed)Again long-term studies required for both neonate and mother.二甲双呱应用组围产结局与二甲双呱应用组围产结局与insulin组无差别，孕妇组无差别，孕妇接受性好，但远期安全性有待证实。接受性好，但远期安全性有待证实。妊娠期口服降糖药临床应用妊娠期口服降糖药临床应用v胰岛素增敏剂胰岛素增敏剂:二甲双胍二甲双胍 FDA B FDA B 类药物类药物 孕前和妊娠早期应用孕前和妊娠早期应用v二代磺脲类降糖药二代磺脲类降糖药:(:(Glubride,Glubride,格列苯脲格列苯脲)几乎不透过胎盘几
22、乎不透过胎盘 孕孕1313周以后应用周以后应用 Pre-existing DM Many pregnancies unplannedMany women with diabetes not diagnosedvEnsure optimal blood glucose controlvInvestigate and treat any associated hypertension,renal or retinal disease糖尿病合并妊娠围产儿死亡率糖尿病合并妊娠围产儿死亡率围产儿死亡率（围产儿死亡率（%）作者作者国家国家患者患者1型糖尿病型糖尿病2型糖尿病型糖尿病背景人群背景人群Coet
23、zee 1985南非南非8477.73.7(31.3)3.1Sacks 1997美国美国15903.5Gunton 2000澳大利亚澳大利亚8509.10.8Cundy 2000新西兰新西兰5941.34.61.3Dunne 2003英国英国1632.51.0 DPG 2003法国法国4356.64.10.7 Hadden 2003英国英国1612.50.9-2.1Clausen 2005丹麦丹麦3011.76.70.8McElduff 2005澳大利亚澳大利亚1801.25.10.7Cheung NW,et al.Australian and New Zealand Journal of O
24、bstetrics and Gynaecology.2005;45:479-483 妊娠期间接受治疗妊娠期间接受治疗 妊娠期间没有接受治疗妊娠期间没有接受治疗糖尿病合并妊娠和胎儿严重先天畸形发生率糖尿病合并妊娠和胎儿严重先天畸形发生率严重先天畸形发生率（严重先天畸形发生率（%）作者作者国家国家患者患者1型糖尿病型糖尿病2型糖尿病型糖尿病背景人群背景人群Omori 1994日本日本20705.8Towner 1995美国美国33211.72Sacks 1997美国美国159714Gunton 2000澳大利亚澳大利亚6422.29.1Schaefer-Graf 2000美国美国4168.9Bry
25、don 2000英国英国2536.112.2Farrel 2002新西兰新西兰7757.24.5Dunne 2003英国英国1829.90.9DPG 2003法国法国4354.53.42.2Clausen 2005丹麦丹麦3012.96.72.9McElduff 2005澳大利亚澳大利亚1806101.1-2.1Cheung NW,et al.Australian and New Zealand Journal of Obstetrics and Gynaecology.2005;45:479-483糖尿病者妊娠前血糖控制目标糖尿病者妊娠前血糖控制目标目标目标 血浆（血浆（mmol/L）全血全
26、血mmol/L空腹和餐前血糖空腹和餐前血糖 4.4-6.1 3.9-5.6餐后餐后2h血糖血糖 5.6-8.6 5.0-7.8HbA1c 7%，尽可能降到正常，尽可能降到正常避免低血糖避免低血糖vTight control of blood glucose levels Congenital malformation Ophthalmology consult Insulin secretion is higher after meals24 hour clockTop line,pregnancyLower line,non-pregnantInsulinuU/mlPregnancy(top
27、 line)Non-pregnant(lower line)孙伟杰，杨慧霞等（孙伟杰，杨慧霞等（2005）中华围产医学杂志中华围产医学杂志Prenatal Obstetric ManagementvPrenatal diagnosisvAssessing fetal growthvPeriodic fetal monitoring from 32GWs (NST、AFI)vPlan Timing and Route of DeliveryvConfirmation of fetal maturityvWith well-controlled blood glucose,the time of
28、delivery is before the estimated due datevGDMA1:40GWsvGDMA2/Pre-GDM:38-39GWsvAmniocentesis only for uncontrolled GDM or early delivery(37 GWs)vRisk of dystociavRisk of shoulder dystociavReduced insulin requirement postpartumvLong-term counselingPre-gestational Diabetes Mellitus(Summary)vProvide prec
29、onception carevOptimize glucose and avoid hypoglycemia.vEvaluate fetal development and growth.vManage renal,eye,or other end organ damage.vAssess mother for complications and fetus for well-being.vEncourage breast-feeding,contraception and preconception care.Neonatal monitoringvAvoid neonatal hypogl
30、ycemia:early feedingvExamine for congenital malformationsvNRDSvPolycytemiavBirth trauma鼓励母乳喂养鼓励母乳喂养/Postpartum Management of GDMvFBG is measured before dischargev75g 2-hr OGTT is repeated between 6-12 weeks after delivery v A 26-year-old gravida 2，para 1001 Hispanic female presents for her initial p
31、renatal visit.v According to her last menstrual period,she is at approximately 16 weeks of gestation.v She discloses her obstetric history of a previous uncomplicated vaginal delivery of a 4560-g infant at 40weeks of gestation.She denies any personal h-X of diabetes，but her father has insulin-depend
32、ent diabetes.v Physical examination demonstrates a moderately obese woman,with a weight of 195 lb and a height of 62 inches.Diabetes Begets DiabetesMetzger B.Clin Obstet&Gynecol 2007.Yang Huixia,GDM Diagnosis and Management Strategy-Some Evidence from China (8th DOHaD,2013)The Effect of Lifestyle Counseling as Prevention of Gestational Diabetes Mellitus:A Cluster-Randomized Controlled Trial (8th DOHaD,2013)Living with diabetes and pregnancy in China:difficulties and coping strategies (IDF,2013)The current situation with respect to diagnose GDM in China (7th DIP,2013)谢谢！谢谢！
