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European Journal of -18-0130 of gestationaldiabetesmellitus (GDM)hasincreasedfrom 35.7% in2013Chinarespectively ( The prevalenceofdiabetesand prediabeteswere10.9%and Introduction GDM. andprediabetes,withthehighestriskatfirst 3–4 yearsafterdelivery, compared withthosewithout Conclusions 30 years atdeliveryandnormalweightoverweightparticipants. of postpartumdiabetesandprediabetesweresignificantpersistentwhenstratifiedbyyoungerolder than 2.62) forprediabetescomparedwithwomenwithoutGDM.ThepositiveassociationsbetweenGDMandtherisks GDM hada13.0-foldmultivariable-adjustedrisk(95%CI:5.54-30.6)fordiabetesand2.15-fold1.76- mean follow-upextendedto4.40 years,121diabetesand616prediabetescaseswereidentified. Women withprior those withoutit,were76.1(95%CI:23.6–246)fordiabetesand25.418.2–35.3).When the prediabetes wereidentified.Multivariable-adjustedhazardratiosamongwomenwithpriorGDM,compared with Results with andwithoutGDM. proportional hazardsregressionwasusedtoassessrisksofpostpartumdiabetesandprediabetesbetweenwomen criteria. Postpartumdiabetesandprediabeteswereidentifiedafterastandardoralglucosetolerancetest.Cox without GDMwhoparticipatedintheurbanuniversalscreeningsurveybyusingWorld HealthOrganization’s Subjects andmethods diabetes mellitus(GDM)duringpregnancy. Aims Abstract *(Y ShenandPWang contributed equallytothiswork) Nova Scotia,Canada Tianjin MedicalUniversity, Tianjin, China,and Public Health,UniversityofHelsinki,Finland, Development, NationalInstitutesofHealth,Bethesda,Maryland,USA, 4 Tong UniversityAffiliated SixPeople’s Hospital,Shanghai,China, 1 Gang Hu Junhong Leng Yun Shen prediabetes risks:alargeobservationalstudy Gestational diabeteswithand Division ofIntramuralPopulationHealthResearch,EuniceKennedyShriverNationalInstituteChildandHuman Pennington BiomedicalResearchCenter, BatonRouge,Louisiana,USA, https://doi.org/ www.ej Clinical Study Clinical Study : To comparerisksofearlypostpartum diabetesandprediabetesinChinesewomenwithwithoutgestational e-online.org : Duringameanfollow-upof3.53 yearspostpartum,90incidentcasesdiabetesand599 1 1 , 10.1530/EJE 2 : ThepresentstudyindicatedthatwomenwithpriorGDM hadsignificantlyincreasedrisksforpostpartum , *, Peng Wang 3 , Jing Wang -18-0130 : Tianjin GDMobservationalstudyincluded1263womenwithahistoryofand705 1 3 , 3 *, Leishen Wang , Huiguang Tian © 2018EuropeanSociety ofEndocrinology Y Shen,PWang andothers 8 Population CancerResearchprogram,DalhousieUniversity, Halifax, 1 ). Theprevalence Printed inGreatBritain 7 Department ofEpidemiology, SchoolofPublicHealth, 3 3 , Shuang Zhang , Cuilin Zhang 3 Tianjin Women’s andChildren’s HealthCenter, Tianjin, China, 5 Dasman DiabetesInstitute,Dasman,Kuwait, 2 Department ofEndocrinologyandMetabolism,ShanghaiJiao that thehealthcarecosts associated withdiabetesand close totheUSlevel(~7%) ( 2.4% in1999to8.1%2012 inurbanChina( Diabetes riskinGDMwomen 4 , Jaakko Tuomilehto Published byBioscientifica Ltd. 3 , Huikun Liu 3 , Weiqin Li 5 , 6 Downloaded fromBioscientifica.com at09/27/202101:23:17PM , Xilin Yang 3 , Nan Li 4 6 Department of ). Currently, itisestimated (2018) Endocrinology European Journal of [email protected] Email to GHu should beaddressed Correspondence 3 179 7 , Wei Li

, Zhijie Yu 179 :1 , 51–58

3 , 2 , 8 and 3 51 ), now –58 via freeaccess European Journal of Endocrinology www.eje-online.org 71 681 werefreeofGDM( among whom 4644 women were diagnosed as GDM and Totally womenwerescreenedfrom 2005to2009, 76 325 Study samples ≥ either diabetes(fastingglucose WHO criteria:a75-gglucose2-hOGTTresultconfirming Children’s HealthCenter. GDMdiagnosiswasmadeasper load wouldbeperformedattheTianjin Women’s and was over 7.8 load at26–30gestationalweeks.Ifthe1-hglucoselevel We useda1-hglucosescreeningtestwith50 rate wasreportedtobe WHO’s criteriainallsixcentraldistricts( launched anurbanuniversalscreeningofGDMusing 1999, theTianjin Women’s andChildren’s HealthCenter millionresidents.In districts inTianjin withabout4.3 distance bytrainfromBeijing.Therearesixcentral Tianjin is the fourth largest city in China, only 30-min Tianjin GDMscreening project Subjects andmethods ofGDM. and withoutahistory postpartum diabetes and prediabetes among women with study,observational weaimedtoinvestigaterisksofearly of GDM. In the present analysis of the Tianjin GDM test (OGTT)amongwomenwithandwithoutahistory and prediabetesbyusingastandardoralglucosetolerance fewstudieshaveassessedearlypostpartumdiabetes very using World Health Organization (WHO)’s criteriaand by carried out an urban GDM universal screening survey postpartum diabetes.Untilnow, nopreviousstudieshave during pregnancyanddiagnosticcriteriamethodsof BMI, ethnicity, diagnosticcriteriaandmethodsofGDM periods, maternalage,pre-pregnancyandpostpartum different conditionsincludingpostpartum diabetes in women with prior GDM might change at high-risk population.However, therisksofpostpartum to preventtheprogressiondiabetesorprediabetesinthis women withpriorGDMsuggestearlylifestyleintervention Studies ofpostpartumriskdiabetesandprediabetesin higher risksofdiabetesandprediabeteslaterinlife( per year( GDM intheUnitedStates are $278 billion and $1.3 billion 11.1 Clinical Study It iswellrecognizedthatwomenwithpriorGDMsuffer mmol/L) orimpairedglucosetolerance(IGT)(2-h ≥ 5 7.8 and ). mmol/L, another 2-h OGTT with 75 < mlL ( 11.1 mmol/L) > 91% between1999and2008( Supplementary Fig. 1Supplementary ≥ Y Shen,PWang andothers 7 7 mmol/L or2-hglucose ). 2 ). Thescreening , seesection g glucose g glucose 6 2 ). ). participants providedwritteninformedconsent. Tianjin Women’s andChildren’s HealthCenter. Allthe was approvedbytheHumanSubjectsCommitteeof newly diagnosed diabetes at baseline survey. The study care’ groupand83 children ofGDMwomenwhowere matched tothe594childrenofGDMwomenin‘usual and theirchildren with birthdates and sexfrequency- Tianjin study705non-GDMwomen GDMobservational in theTGDMPP. Inparallel,wealsoenrolledinthe group ( women withGDMwererandomizedintoanintervention diabetes accordingtotheOGTTresultsandrest1180 these 1263womenwithGDM,83werenewlydiagnosed and anOGTTbetweenAugust2009 and July2011.Of includingaquestionnaire finished thebaselinesurvey (TGDMPP) ( Tianjin GestationalDiabetes MellitusPreventionProgram We invitedall4644GDMwomentoparticipateinthe on performance of3-day24-hfoodrecords( record collections taught by a dietician. The for dietary completed the 3-day 24-h food records using methods activities) atthepostpartumbaselinesurvey. Theyalso (the frequencyanddurationofleisure-timesedentary habits,passiveandphysicalactivity and beveragesduringthepastyear)( frequency and quantity of intake of 33 major food groups food frequencyquestionnaire(FFQ)tomeasurethe habits (a self-administered number of children), dietary (pre- weight,weightgaininpregnancyand diabetes andhypercholesterolemia), pregnancyoutcomes (, and hypertension),medicalhistory heartdisease(CHD),stroke,cancer (diabetes, coronary ofGDM,familyhistory income andoccupation),history their socio-demographics(age,maritalstatus,education, All studyparticipantsfilledinaquestionnaireabout Questionnaires andmeasurements were collectedinallparticipants afteranovernightfastof with womenintheirstanding position.Bloodsamples line costal marginandtheiliac crest onthemid-axillary was measured at the horizontal level between the inferior by thesquareofheightin meters.Waist circumference BMI was calculated as the body weight in kilograms divided standardized protocol byspecially trained research doctors. in2002. Nutrition andHealthSurvey ( and theabovequestionnaireonassessingphysicalactivity Diabetes riskinGDMwomen 13 , supplementary data supplementary Body weightandheightweremeasuredusingthe 14 n ) have been validated in the China National

= 586) and a ‘usual care’ control group ( 8 , 9 , 10 , 11 ). Finally, 1263womenwithGDM givenattheendofthisarticle). Downloaded fromBioscientifica.com at09/27/202101:23:17PM 179 12 ), alcoholintake, :1 12 ), theFFQ( n =594) 52 12 via freeaccess ), European Journal of Endocrinology older after delivery and younger at baseline survey.older after delivery Their were givenin General characteristicsofthe studypopulationatbaseline Results version 24.0(IBMCorp.). were performedbyIBMSPSSStatisticsforWindows, considered statisticallysignificant.Allstatisticalanalyses (Model 2),andfurtherforBMI3). drinking, energyintakesoffat,proteinandcarbohydrate activity, fiber, sleepingtime,dietary sweetenedbeverage passive smoking, alcohol drinking, leisure-time physical ofdiabetes, smoking, family income, family history were adjustedforage(Model1),andtheneducation, between womenwithandwithoutGDM.Allanalyses to assessrisksofpostpartumdiabetesandprediabetes Cox proportionalhazardregressionanalysiswasused variables betweenwomenwithGDMandwithoutGDM. comparison ofcontinuousvariablesandcategorical Standard Statistical analysis women in thecontrolgroup at the year 3 follow-up visit). group andnon-GDMwomenatbaselinesurvey, andGDM postpartum follow-up(GDMwomenintheinterventional andextended and non-GDMwomenatbaselinesurvey) follow-up periods:earlypostpartum(bothGDM visits. The present study included two different postpartum subsequent annualOGTTduringthe3-yearfollow-up control groupsintheTGDMPPfinishedbaselineand cases. Untilnow, and GDMwomeninbothintervention examination werealsoincludedintothetype2diabetes < and impaired fasting glucose (fasting glucose glucose was definedasfastingglucose ( We usedAmericanDiabetesAssociation(ADA)’s criteria Definition ofpostpartumdiabetesandprediabetes 4.42% forglucose. (Toshiba TBA-120FR,Japan).Coefficientofvariancewas Plasma glucosewasmeasuredonanautomaticanalyzer of diabetesweregivenastandard75-gglucoseOGTTtest. at least12 15 11.1 mmol/L).Thoseusingantidiabeticdrugsinthe Clinical Study ) for the diagnosis of diabetes and prediabetes. Diabetes < 7.0 ≥ mmol/L) orIGT(2-hglucose 11.1 t h. Participants without a self-reported history h. Participantswithoutaself-reportedhistory testandchi-squarewereusedinthe mmol/L. Prediabetes was defined as either al 1 Table . Women withGDM wereslightly ≥ Y Shen,PWang andothers 7.0 mmol/L and/or2-h ≥ mlL and 7.8 mmol/L ≥ P 5.6 mmol/L

< .5 was 0.05 23.6–246) fordiabetesand25.4(95%CI:18.2–35.3) compared withthosewithoutGDM,were76.1(95%CI: – Model3)hazardratiosamongwomenwithpriorGDM, energy intakesoffat,proteinandcarbohydrate,BMI fiber,sleeping time, dietary sweetened beverage drinking, smoking, alcoholdrinking,leisure-timephysicalactivity, ofdiabetes,smoking,passive family income,history respectively. Multivariable-adjusted (age, education, years and49.3/1000person-yearsinnon-GDMwomen, person-years inGDMwomen,and1.73/1000person- prediabetes were28.7/1000person-yearsand150.3/1000 cases ofprediabetes.Theincidentratesdiabetesand there were90incidentcasesofdiabetesand599 compared withthosewhowerefreeofGDM. less physicallyactiveandhadmoreenergyintakesas income. Inaddition,theywerelessalcoholdrinkers, higher. They were less educated and had less family BMI, HbA1C,fastingand2-hglucoseatbaselinewere women (~10%)compared withotherracial/ethnic the highestatfirst3–4 years afterdelivery. compared withwomenwithout GDM,andthisriskwas increased risk ofpostpartumdiabetes and prediabetes ofGDMduringpregnancyhad asignificantly history study,In thislargeGDMobservational womenwitha Discussion interaction the risksofpostpartumdiabetesandprediabetes(all significant interactionsofage,BMIandGDMstatus on women.Therewereno statistically and inbothhealthyweightwomen association wasobserved ( yearsatdelivery 30 were presentinwomenagedyoungerandolderthan GDM and the risks of postpartum diabetes and prediabetes with womenwithoutGDM( fold risk (95% CI: 1.76–2.62) for prediabetes compared adjusted risk (95%CI: 5.54–30.6) for diabetes and 2.15- Women with prior GDM had a 13.0-fold multivariable- 49.3/1000 person-yearsinnon-GDMwomenrespectively. years inGDMwomen,and1.73/1000person-years changed to24.7/1000person-yearsand98.1/1000person- prediabetes. The incident rates of diabetes and prediabetes 121 incidentcasesofdiabetesand616 years,therewere the meanfollow-upextendedto4.40 prediabetes respectively( Diabetes riskinGDMwomen uigama olwu f35 yearspostpartum, During ameanfollow-upof3.53 The prevalenceofGDM is highamongAsian Multivariable-adjusted positiveassociationsbetween > 0.25). al 3 Table Downloaded fromBioscientifica.com at09/27/202101:23:17PM i. 1A Fig. Fig. 1C ). Similarly, thepositive , B , and D 179 and www.eje-online.org :1 al 2 Table Table 2 ). When ). P 53 for via freeaccess European Journal of Endocrinology www.eje-online.org diabetes inwomenwithprior GDMmightchangedueto 8 years ( developed type2diabetes after amedianfollow-upof ofGDMin HongKong,9.0%ofwomenwithahistory ofGDM.InacohortChinese womenlivinghistory diabetes andprediabetesinChinesewomenwith a fewstudiesinvestigatedthepostpartum risksofvery than otherracial/ethnicAmericans( lower BMIandtheprevalenceofoverweight/ the US( diabetes thanotherracial/ethnicwomenwithGDM in Asian AmericanswithGDMaremorelikelytodevelop in USwomen(~7%)( in 1999to8.2%2012( China, theprevalenceofGDMhasincreasedfrom2.4% groups (5–8%)intheUnitedStates( a Energy consumption(kcal/day) Sleeping time(h/day) Leisure-time physicalactivity(%) Current alcoholdrinker(%) Passive smoking(%) Current smoking(%) Family historyofdiabetes(%) Income (%) 13–16 years Education (%) HbA1c (%) HbA1c (mmol/mol) 2-hour glucose(mmol/L) Fasting glucose(mmol/L) Waist circumference(cm) BMI (kg/m duringpregnancy(kg) Duration afterdelivery(years) Age atbaseline(years) Age atdelivery(years) No. ofparticipants Table 1 Dietary intakesareassessedby3-day24-hfoodrecords; Sweetened beveragedrink(%) (%energy) Carbohydrate (%energy) Fat (%energy) Fiber (g/day) ≥ 1–29 0 ≥ 5000–8000 yuanpermonth < ≥ < Clinical Study min perday 30 8000 yuanpermonth 5000 yuanpermonth 16 years 13 years It hasbeensuggestedthat theriskofpostpartum min perday min perday 23 20 Characteristics ofwomenwithandwithoutgestationaldiabetes(GDM),Tianjin, China. 2 ) ). ) althoughAsianAmericansgenerallyhave 4 ). Recentstudieshavefoundthat 2 , a 3 ), nowsimilartothelevel Y Shen,PWang andothers 16.6 52.3 31.1 11.6 1627 7.48 6.14 5.23 75.8 22.9 18.3 5.74 35.4 29.7 16 Non-GDM 21 5.3 35 77.9 33.8 61.7 32.1 55.2 27.1 79.1 15.5 14.2 75.5 10.4 , 705 4.5 4.0 5.4 , ± ± ± ± ± ± ± ± ± ± ± ± ± ±

17 ± ± 22 2.62 6.81 5.65 4.42 0.95 0.2 1.41 0.52 8.26 3.68 6.67 1.19 2.95 2.83 381 3 b P , ). However, valuesbetweennon-GDMandGDMwithearlypostpartumfollow-up. 18 , 19 ). In GDM withearlypostpartum 7.08 5.38 80.6 24.2 16.8 2.29 32.4 30.1 17.0 49.5 33.5 12.2 1676 7.81 follow-up have assessedearlypostpartum diabetesandprediabetes using thestandardWHO’s fewstudies criteria,andvery by based onanurbanGDMuniversal screeningsurvey diabetes. Nopreviousstudies havereportedtheresults some asymptomaticcasesofGDMandpostpartum postpartum diabetes,thesestudiescouldhavemissed symptomatic womenathighrisksofGDMand studies onlyusedelectronicmedicalrecordstoidentify a standardquestionnaire( BMI andmoreweightgainafterGDMdevelopmentby especially amongGDMwomenwithhigherbaseline offollow-up, among GDMwomenduringupto18 years Bao diagnostic criteriaofpostpartumdiabetes.Forexample, BMI, diagnosticcriteriaofGDMduringpregnancyand periods, maternalage,pre-pregnancyandpostpartum different racesandethnicities( 5.6 Diabetes riskinGDMwomen 38 1263 35.7 35.6 36.9 27.5 70.1 22.5 75.5 19.1 78.8 21.8 53.8 7.4 2.1 2.0 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 0.7 2.49 0.97 9.47 3.93 5.99 0.88 3.52 3.50 2.78 7.30 6.34 4.75 1.06 t al et 8 436 . reportedahigherriskofpostpartumdiabetes GDM with extended postpartum Downloaded fromBioscientifica.com at09/27/202101:23:17PM 7.24 5.43 80.6 24.3 16.8 3.65 33.7 30.1 16.7 50.2 33.1 12.3 1704 7.70 follow-up 25 5.6 38 1263 35.7 35.6 36.9 27.5 70.1 22.5 78.1 25.3 71.7 26.9 58.0 ). Sincemostofprevious 7.4 3.0 2.5 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 24 0.7 2.65 0.99 9.48 3.96 5.99 2.17 4.13 3.50 2.68 7.04 6.12 4.62 1.02 8 432 ), differentpostpartum 179 :1 P < < < < < < < < < < < < < < < < < value 0.223 0.006 0.001 0.001 0.01 0.01 0.01 0.001 0.001 0.572 0.355 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.008

54 via freeaccess b European Journal of Endocrinology odds ratiosofdiabetesamong GDMwomencompared A recentreviewhasalso indicated thattheadjusted diabetes comparedwithwomen withoutGDM( prior GDM have aseven-fold higher risk of postpartum of GDMwithpostpartumdiabetesandprediabetes. study providedacomprehensiveandaccurateestimation were excludedinthepresentstudy. Thus, thepresent with asymptomatic diabetes during the earlypregnancy trimester ( finished afastingglucoseexaminationduringthefirst about 95%ofpregnancywomenintheTianjin urbanarea and prediabetesusingtheADA’s criteria.Inaddition, postpartumtoidentifydiabetes at 1–9 years GDM and705womenwithhadastandard OGTT by usingtheWHO’s criteria.All1263womenwithprior the wholepopulation’s GDMuniversalscreeningsurvey womenwhoparticipatedin without GDMfrom76 325 ofGDMand705women 1263 womenwithahistory study was the only study with a large sample size including ofGDM.Tianjin without ahistory GDMobservational by using a standard OGTT among women with and carbohydrate andBMI.GDM,gestationaldiabetesmellitus. beverage drinking,energyintakesoffat,protein,and physical activity, sleepingtime,dietaryfiber, sweetened passive smoking,currentalcoholdrinking,leisure-time family income,historyofdiabetes,currentsmoking, without GDM.Allanalyseswereadjustedforage,education, extended postpartumfollow-up)amongwomenwithand and prediabetes(B,earlypostpartumfollow-upD, postpartum follow-upandC,extendedfollow-up) The cumulativeincidencecurveoftype2diabetes(A,early Figure 1 Clinical Study Two early reviews have reported that women with 26 ). Women withdiabetesbeforepregnancyor Y Shen,PWang andothers 6 , 27 ). postpartum diabetes ( genetic variantsamongwomenwithearlyonsetof include morepronouncedbetacelldefectandsusceptible and then attenuated ( 3–6 years among womenwithGDMincreasedtoapeakatthefirst recent meta-analysisthattheriskofpostpartumdiabetes without GDM, which was similar to the trend from one comparedwithwomen yearsafterdelivery the first3–4 prior GDMhadthehighestriskofpostpartumdiabetesat GDM. Thepresentstudydemonstratedthatwomenwith fold riskforprediabetescomparedwithwomenwithout prior GDMhada13.0-foldriskfordiabetesand2.15- years,womenwith mean follow-upextendedto4.40 yearspostpartum.Whenthe mean follow-upof3.53 prediabetes comparedwithwomenwithoutGDMata had a76.1-foldriskfordiabetesand25.4-fold The presentstudyfoundthatwomenwithpriorGDM the onsetofpostpartumdiabetes( that antepartumcharacteristicsmightalsocontributeto delivery were5.37,16.55and8.20,respectively( delivery with non-GDMwomenat more attention.Theearlypostpartum 2-hOGTTmight years at delivery, which should be taken than age 30 prediabetes thanwomenwith priorGDMwhowereolder tended tohavehigherrisks forpostpartumdiabetesand yearsatdelivery GDM whowereyoungerthan age30 of GDM.Meanwhile,wealsonoticedthatwomenwith women withahistory and prediabetesamongoverweight strongly recommendedtopreventordelaytype2diabetes on weightlossis early postpartumlifestyleintervention definite riskfactorfordiabetesandprediabetes.Thus, the results in other studies ( weight womenwithoutGDM,whichwassimilarwith and normal with priorGDMcomparedoverweight risk forpostpartumdiabetesthannormalweightwomen women with prior GDM seemed to show a much higher ontheprogressofdiabetes. intervention trial toevaluatetheeffectofearlypostpartumlifestyle delay theonsetoftype2diabetes.TGDMPPisanongoing inordertopreventor postpartum lifestyleintervention a highriskpopulationthatshouldbetargetedforearly Thus, weimpliedthatwomenwithpriorGDMrepresents factors remainsunknownandneedsfurtherstudies. diabetes. Whetherthisrisktrendresultedfromother compared with women with late onset of postpartum among womenwithearlyonsetofpostpartumdiabetes the GDMwomen’s insulintreatmentduringpregnancy or postpartumBMI,weightgainduringpregnancyand cohort, therewerenosignificantdifferencesinantepartum Diabetes riskinGDMwomen In subgroupanalysesofthepresentstudy, overweight 29 Downloaded fromBioscientifica.com at09/27/202101:23:17PM ). Severalstudies have confirmed < ,36ad61 yearsafter 3, 3–6and6–10 32 28 , 30 ). Explanations might 33 , 179 31 ). Overweight is a ). Overweight www.eje-online.org ). However, inour :1 55 28 via freeaccess ). European Journal of Endocrinology www.eje-online.org a GDM womenwithextendedpostpartumfollow-up(mean4.40 years)

Women withextendedpostpartumfollow-up(mean4.40 years) Women withearlypostpartumfollow-up(mean3.53 years) Table 3 and microvascular ( younger ageusuallyhavemuchhigherrisksofmacro-( younger age.Patientsdiagnosedastype2diabetesata glucose intoleranceastheydevelopedGDMevenata These womenmaybeofhighergeneticsusceptibilityto ofdiabetes. were moreexposedtopositivefamilyhistory inourcohort GDM womenwhowereyoungeratdelivery the higherriskofwomenatayoungerage.Inaddition, prediabetes at ayounger age, which could partly explain help identifyasymptomaticwomenwithdiabetesand Multiple adjustedhazardratios Pearson-years carbohydrate consumption,andsweetenedbeveragedrinking;Model3wasadjustedforfactorsin2alsoBMI. passive smoking,currentalcoholdrinking,leisure-timephysicalactivity, sleepingtime,energyconsumption,fiber, fat,proteinand was adjustedforage;Model2age,education,familyincome,historyofdiabetes,currentsmoking, Table 2 beverage drinkingandBMI,otherthan thevariablesforstratification; current alcoholdrinking,leisure-time physicalactivity, sleeping time,energyconsumption,fiber, fat,proteinandcarbohydrateconsumption,sweetened a Multiple adjustedhazardratios Pearson-years GDM womenwithearlypostpartumfollow-up(mean3.53 years) Excluding type2diabetes. Excluding type2diabetes; Model 3 No. ofparticipants Model 2 Age atdeliverygroups(years) BMI (kg/m Age atdeliverygroups(years) BMI (kg/m Model 1 No. ofcases Model 3 Model 2 Model 1 No. ofcases No. ofparticipants Clinical Study ≥ < ≥ < ≥ < ≥ < 25 30 30 25 30 30 25 25 Hazard ratioofdiabetesandprediabetesamongwomenwithwithoutGDMbyvarioussubgroups. Hazard ratioofdiabetesandprediabetesamongwomenwithwithoutGDMatdifferent follow-upperiod.Model1 2 2 ) ) c c b All analyseswereadjustedforage,education, familyincome,historyofdiabetes,currentsmoking,passive smoking, c c 35 ) thanthose developing Y Shen,PWang andothers Non-GDM Non-GDM 1 1 1 1 1 1 1 1 4052 4052 705 705 1 1 1 7 1 1 1 7 34 b c All ) P Diabetes b forinteraction Diabetes based ontheADA’s criteriaaftera2 diagnosis ofpostpartumdiabetesandprediabeteswas by usingtheWHO’s criteriaaftera2 on thewholepopulation’s GDMuniversalscreening diagnoses ofGDMat26–30gestationalweekswerebased ofGDM. among womenwithahistory Policy regardingpreventionoftheprogressdiabetes greatly promotefavorablechangesinthePublicHealth type 2diabeteslater. Thefindingsofthepresentstudywill Diabetes riskinGDMwomen 7.91 (2.36–26.5) 19.1 (5.76–63.3) 22.0 (5.26–91.9) 8.45 (2.67–26.8) 60.0 (9.93–363) 50.2 (13.1–193) 132 (22.6–774) 164 (18.3–1464) 13.0 (5.54–30.6) 15.6 (6.62–36.7) 17.0 (7.92–36.6) 76.1 (23.6–246) 91.0 (28.2–294) 113 (37.3–346) A uniqueadvantageofthepresentstudyisthat GDM 1263 4609 2886 1263 GDM 114 83 > 0.25. Downloaded fromBioscientifica.com at09/27/202101:23:17PM Non-GDM Non-GDM 4014 4014 1 1 1 1 1 1 1 1 198 698 198 698 1 1 1 1 1 1 Prediabetes Prediabetes 179 h 75 h 75 :1 2.14 (1.57–2.91) 2.20 (1.69–2.85) 1.78 (1.29–2.46) 2.47 (1.92–3.18) 29.3 (16.8–50.9) 28.6 (18.2–44.6) 25.3 (14.3–44.8) 26.8 (17.8–40.5) 2.15 (1.76–2.62) 2.30 (1.89–2.80) 2.20 (1.85–2.62) 25.4 (18.2–35.3) 27.0 (19.5–37.5) 29.0 (21.2–39.5) a g OGTT. Our g OGTT. The a GDM 4262 1149 2668 1180 GDM 418 401 56 via freeaccess European Journal of Endocrinology of themanuscriptanddecisiontosubmit themanuscriptforpublication. analysis andinterpretationofthedata, preparation,revieworapproval role inthedesignandconductof thestudy, collection,management, Development, NationalInstitutesof Health.Thefundingsourceshadno of EuniceKennedyShriverNational InstituteofChildHealthandHuman Health. DrCuilinZhangissupported bytheIntramuralResearchProgram of GeneralMedicalSciences(U54GM104940)theNationalInstitutes of Digestive andKidneyDiseases(R01DK100790)theNationalInstitute partly supportedbythegrantfromNationalInstituteofDiabetesand and Children’s HealthCenter andTianjin PublicHealthBureau.DrHuwas for CollaborativeResearchbetweenChinaandEurope,Tianjin Women’s Study ofDiabetes(EFSD)/ChineseSociety(CDS)/Lillyprogramme This studyissupportedbythegrantfromEuropeanFoundationfor Funding perceived asprejudicingtheimpartialityofthisstudy. The authorsdeclarethatthereisnoconflictofinterestcould be Declaration ofinterest EJE-18-0130. This is linked to the online version of the paper at Supplementary data ofGDM. women withahistory prevent and delay diabetes and prediabetes risk among delivery. might Anearlypostpartumlifestyleintervention yearsafter and thisriskwasthehighestatfirst3–4 with priorGDMcomparedthosewithoutGDM, risk ofpostpartumdiabetesandprediabetesinwomen considered inthepresentstudy. ofmorethanoneparity( a history included intheTianjin GDMscreeningprojecthave diabetes ( parity wereassociatedwithanincreasingriskoftype2 results. Ithasbeenconsideredthatincreasingnumbersof in Chinathanothercountries,whichmayinfluencethe policy from1979to2015( diagnostic criteria for GDM. Finally, duetothe one-child 3-h glucoseduringpregnancysinceweusedtheWHO’s be verified. Second, we have no data on 1-h glucose and whether otherdifferences between groups existedcannot tests between those returned and those not returned, IGT anddiabetesat26–30gestationalweeksOGTT in age, 2-h glucose, fasting glucose, the prevalence of of allGDMwomen.Althoughtherewerenodifferences is thereturnrateofinitialinvitationwithonly27% ofGDM.Onelimitationthisstudy without ahistory study isthelargesamplesizeofbothwomenwithand and prediabetes.Anotherimportantstrengthofour accurate estimationofGDMwithpostpartumdiabetes study istheonlytoprovideacomprehensive and Clinical Study In conclusion,wereportedasubstantiallyincreased 37 ). However, since only 2.44% of thewomen 36 ), thebirthrateswerelower Y Shen,PWang andothers 2 ), paritybiasisnot https://doi.org/10.1530/ References Tianjin GestationalDiabetesMellitusPreventionProgram. The authors would like to appreciate all families for participating in the Acknowledgements of thedataandaccuracyanalysis. access toallthedatainstudyandtakesresponsibilityforintegrity intellectual content.GHistheguarantorofthisworkand,assuch,hadfull content. CZ,XYandZcriticallyrevisedthemanuscriptforimportant analyses andcriticallyrevisedthemanuscriptforimportantintellectual S Z,HL,WNJLandacquireddata,performedstatistical critically revisedthemanuscriptforimportantintellectualcontent.LW, analyses anddraftedthemanuscript.HTJdesignedstudy Y S,PWandGHdesignedthestudy, acquireddata,performedstatistical Author contributionstatement

Diabetes riskinGDMwomen 10 2 1 9 8 7 6 5 4 3 Zhang F, Dong L,Zhang C,Li B,Wen J, Gao W, Sun S,Lv F, Wang L, Gao P, Zhang M,Huang Z,Zhang D,Deng Q,Li Y, Zhao Z, Liu H, Zhang S,Wang L, Leng J,Li W, Li N,Li M,Qiao Y, Tian H, Liu H, Zhang C,Zhang S,Wang L, Leng J,Liu D,Fang H,Li W, Hu G, Tian H, Zhang F, Liu H, Zhang C,Zhang S,Wang L, Liu G, WHO Consultation. Bellamy L, Casas JP, Hingorani AD&Williams D. Type 2diabetes Dall TM, Yang W, Halder P, Pang B,Massoudi M,Wintfeld N, American DiabetesAssociation.Gestationaldiabetesmellitus. Leng J, Shao P, Zhang C,Tian H, Zhang F, Zhang S,Dong L,Li L, doi.org/10.1001/jama.2017.7596) prediabetes inChina2013. Qin X, Jin D diabres.2015.11.007) Clinical Practice Chinese womenwithgestationaldiabetes. HbA1c inpregnancyandthepostpartum riskofdiabetesamong Tuomilehto J org/10.1002/oby.20722) diabetes women. and weightchangeonpostpartumdiabetesriskamonggestational Yu Z, Yang X diabres.2012.09.015) and ClinicalPractice program. the feasibilityoflifestyleintervention Program: studydesign,methods,and1-yearinterimreporton Yu Z, Yang X Diabetes Mellitus. 1:DiagnosisandClassificationof Mellitus anditsComplications.Part S0140-6736(09)60731-5) analysis. mellitus aftergestationaldiabetes:asystematicreviewandmeta- 3172–3179. gestational diabetesmellitus,andprediabetes. blood glucoselevelsin2012:diagnosedandundiagnoseddiabetes, Semilla AP, Franz J&Hogan PF. Theeconomicburdenofelevated org/10.2337/diacare.26.2007.S103) Diabetes Care doi.org/10.1371/journal.pone.0121029) based studyinTianjin, China. its riskfactorsinchinesepregnantwomen:aprospectivepopulation- Yu Z, Chan JC 5491.2010.03205.x) diabetes mellitusinChinesewomenfrom1999to2008. Tian H, Tuomilehto J 2011 Lancet (https://doi.org/10.2337/dc14-1036) 2003 et al et al et al et al 28 et al 2016 2009 Geneva:World HealthOrganisation,1999. . Prevalenceandethnicpatternofdiabetes 652–657. . Jointeffectsofpre-pregnancybodymassindex . Tianjin GestationalDiabetesMellitusPrevention Obesity . Fastingand2-hourplasmaglucose, and . Prevalenceofgestationaldiabetesmellitusand 26 2012 Definition, DiagnosisandClassificationofDiabetes 112 373 et al (Supplement1)S103–S105. 2014 30–36. 1773–1779. 98 . Increasingprevalenceofgestational Downloaded fromBioscientifica.com at09/27/202101:23:17PM (https://doi.org/10.1111/j.1464- 508–517. JAMA 22 PLoS ONE 1560–1567. (https://doi.org/10.1016/j. 2017 (https://doi.org/10.1016/ (https://doi.org/10.1016/j. 2015 317 Diabetes Research and 179 (https://doi. 2515–2523. Diabetes Care www.eje-online.org 10 :1 Diabetes Research e0121029. (https://doi. Diabetic (https:// 2014 (https:// 57 37 via freeaccess

European Journal of Endocrinology www.eje-online.org

20 24 23 22 21 19 18 17 16 15 14 13 12 11 Clinical Study Xiang AH, Li BH,Black MH,Sacks DA,Buchanan TA, Jacobsen SJ Tam WH, Yang XL, Chan JC, Ko GT, Tong PC, Ma RC,Cockram CS, Shai I, Jiang R,Manson JE,Stampfer MJ,Willett WC, Colditz GA& Oza-Frank R, Ali MK,Vaccarino V &Narayan KM. AsianAmericans: Wang Y, Chen L,Xiao K,Horswell R,Besse J,Johnson J,Ryan DH Dabelea D, Snell-Bergeon JK,Hartsfield CL,Bischoff KJ,Hamman RF Ferrara A, Kahn HS,Quesenberry CP, Riley C&Hedderson MM.An Chu SY, Abe K,Hall LR,Kim SY, Njoroge T&Qin C.Gestational American DiabetesAssociation.2.Classificationanddiagnosisof Ma G, Luan D,Li Y, Liu A,Hu X,Cui Z,Zhai F&Yang X. Physical Ma G, Luan D,Liu A,Li Y, Cui Z,Hu X&Yang X. Theanalysisand Li YP, He YN,Zhai FY, Yang XG, Hu XQ,Zhao WH&Ma GS. Li W, Zhang S,Liu H,Wang L, Zhang C,Leng J,Yu Z, Yang X, Tian H Wang Y, Chen L,Horswell R,Xiao K,Besse J,Johnson J, (https://doi.org/10.1007/s00125-011-2330-2) gestational diabetesmellitus. & Lawrence JM.Racialandethnicdisparitiesindiabetesriskafter Reviews ofgestationaldiabetes. history diabetes andmetabolicsyndromeinChinesewomenwithapast Sahota D &Rogers MS.Progressiontoimpairedglucoseregulation, doi.org/10.2337/dc06-0057) 20-year follow-upstudy. Hu FB. Ethnicity, obesity, andriskoftype2diabetesinwomen:a org/10.2337/dc09-0573) weight classifications. diabetes prevalenceacrossU.S.andWorld HealthOrganization jwh.2011.3318) of Women’s Health gestational diabetesmellitusandriskoftype2diabetes. Ryan DH &Hu G.Racialdifferencesintheassociationbetween (https://doi.org/10.1089/jwh.2011.2838) louisiana, 1997–2009. & Hu G.Increasingincidenceofgestationaldiabetesmellitusin (https://doi.org/10.2337/diacare.28.3.579) Colorado GDMScreeningProgram. mellitus (GDM)overtimeandbybirthcohort:KaiserPermanenteof & McDuffie RS.Increasingprevalenceofgestationaldiabetes (https://doi.org/10.1097/01.AOG.0000113623.18286.20) California, 1991–2000. increase intheincidenceofgestationaldiabetesmellitus:Northern 265–268. diabetes mellitus:allAsiansarenotalike. 2018 diabetes: standardsofmedicalcareindiabetes-2018. 1) 113–118. employed populationinChina. activity levelanditsassociationwithmetabolicsyndromeamongan org/10.3321/j.issn:0512-7955.2007.03.007) population. evaluation ofaphysicalactivityquestionnaireChineseemployed doi.org/10.3760/j:issn:0253-9624.2006.04.014) methods. survey Comparison ofassessmentfoodintakesbyusing3dietary 2533–2539. with priorgestationaldiabetesmellitus. and insulinresistanceamongobesenonobeseChinesewomen & Hu G.Differentassociationsofdiabeteswithbeta-celldysfunction 41 2007 S13–S27. (https://doi.org/10.1016/j.ypmed.2009.07.001) Zhonghua Yu FangYi XueZaZhi (https://doi.org/10.2337/dc14-0573) (https://doi.org/10.1111/j.1467-789X.2007.00451.x) Ying Yang XueBao 23 485–489. (https://doi.org/10.2337/dc18-S002) 2012 Diabetes Care Journal ofWomen’sJournal Health Obstetrics andGynecology Diabetes Care 21 (https://doi.org/10.1002/dmrr.741) 628–633. Diabetologia 2007 Diabetes/ Research and Obesity Review 2009 Diabetes Care 29 2006 Y Shen,PWang andothers 217–221. (https://doi.org/10.1089/ Diabetes Care 2011 32 2006 Preventive Medicine 29 1644–1646. 2008 1585–1590. 54 2012 40 2004 2005 (https://doi. 3016–3021. 273–280. 9 Diabetes Care 2014 (Supplement 21 103 28 319–325. (https://doi. 579–584. 526–533. 37 (https:// 2009 Journal (https://

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Accepted 9May2018 Revised versionreceived30April2018 Received 12February2018

Diabetes riskinGDMwomen 30 29 28 27 26 25 35 34 33 32 31 37 36 Jang HC. GestationaldiabetesinKorea:incidenceandriskfactors Kwak SH, Choi SH,Jung HS,Cho YM,Lim S,Cho NH,Kim SY, Song C, Lyu Y, Li C,Liu P, Li J,Ma RC&Yang X. Long-termriskof Kim C, Newton KM&Knopp RH.Gestationaldiabetesandthe Dong L, Liu E,Guo J,Pan L,Li B,Leng J,Zhang C,Zhang Y, Li N& Bao W, Yeung E, Tobias DK, Hu FB,Vaag AA, Chavarro JE,Mills JL, Li L, Ji L,Guo X,Ji Q,Gu W, Zhi X,Li X,Kuang H,Su B,Yan J Huo X, Gao L,Guo L,Xu W, Wang W, Zhi X,Li L,Ren Y, X,Sun Z Lee AJ, Hiscock RJ,Wein P, Walker SP &Permezel M.Gestational Cianni GD, Ghio A,Resi V&Volpe L. Gestational diabetesmellitus: Buchanan TA, Xiang A,Kjos SL,Lee WP, Trigo E, Nader I, Naver KV, Lundbye-Christensen S,Gorst-Rasmussen A,Nilas L, Zeng Y &Hesketh T. TheeffectsofChina’s universaltwo-child of diabetesinwomenwithpreviousgestationaldiabetes. E744–E752. mellitus. diabetes atearlyorlatepostpartumaftergestational Park KS &Jang HC.Clinicalandgeneticriskfactorsfortype2 obr.12645) women. a systematicreviewandmeta-analysiswithmorethan2million durationsaftergestationaldiabetes: diabetes inwomenatvarying 25 incidence oftype2diabetes:asystematicreview. (https://doi.org/10.1016/j.diabres.2013.10.017) infancy. gestational weeksandoffspringgrowthdevelopmentinearly Hu G. Relationshipbetweenmaternalfastingglucoselevelsat4–12 015-3537-4) Diabetologia ofgestationaldiabetesmellitus:aprospectivecohortstudy.a history mellitus inrelationtoBMIandweightchangeamongwomenwith Grunnet LG, Bowers K,Ley SH S2213-8587(15)00508-2) Diabetes andEndocrinology late-onset type2diabetesinChina:across-sectionalstudy. et al Diabetes Care analysis. type 2diabetes:aretrospectivecohortstudyusingsurvival diabetes mellitus:clinicalpredictorsandlong-termriskofdeveloping org/10.2217/whe.09.76) in youngwomen. an opportunitytopreventtype2diabetesandcardiovasculardisease doi.org/10.2337/diab.47.8.1302) 2 diabetesinLatinowomen. characteristics thatpredictpostpartumglucoseintoleranceandtype Bergner EA, Palmer JP&Peters RK.Gestationaldiabetes:antepartum dmj.2011.35.1.1) and MetabolismJournal (https://doi.org/10.1111/j.1464-5491.2010.03169.x) Danish nationwidebirthcohort. Secher NJ, Rasmussen S&Ovesen P. Parityandriskofdiabetesina 6736(16)31405-2) policy. jdiacomp.2014.08.010) and ItsComplications with earlyversuslateonsetoftype2diabetes. careChinese Prevalence ofmicrovasculardiseasesamongtertiary 1862–1868. . Riskofnon-fatalcardiovasculardiseasesinearly-onsetversus Lancet Diabetes Research andClinicalPractice Obesity Reviews Journal ofClinicalEndocrinologyandMetabolism Journal 2015 (https://doi.org/10.1210/jc.2012-3324) 2007 2016 (https://doi.org/10.2337/diacare.25.10.1862) 58 Women’s Health 30 388 2015 1212–1219. 878–883. 2011 2018 1930–1938. 2016 29 Downloaded fromBioscientifica.com at09/27/202101:23:17PM 35 Diabetes 32–37. 19 et al 1–7. 4 (https://doi.org/10.2337/dc06-1816) 421–429. Diabetic Medicine 115–124. (https://doi.org/10.1007/s00125- 2010 . Long-termriskoftype2diabetes (https://doi.org/10.1016/S0140- (https://doi.org/10.4093/ 1998 (https://doi.org/10.1016/j. 6 97–105. (https://doi.org/10.1111/ 47 179 (https://doi.org/10.1016/ 2013 1302–1310. Journal ofDiabetes Journal :1 Diabetes Care 2011 (https://doi. 102 210–217. 2013 28 Diabetes 43–47. (https:// Lancet 98 2002 et al 58 via freeaccess .