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Diabetesmellitusinpregnancy:Screeninganddiagnosis
OfficialreprintfromUpToDate
www.uptodate.com2014UpToDate

Diabetesmellitusinpregnancy:Screeninganddiagnosis
Authors
DonaldRCoustan,
MD
LoisJovanovic,MD

SectionEditors
DavidMNathan,MD
MichaelFGreene,
MD

DeputyEditor
VanessaABarss,
MD,FACOG

Disclosures:DonaldRCoustan,MDNothingtodisclose.LoisJovanovic,MD
Nothingtodisclose.DavidMNathan,MDNothingtodisclose.MichaelF
Greene,MDNothingtodisclose.VanessaABarss,MD,FACOGEmployeeof
UpToDate,Inc.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsfor
referencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Nov2014.|Thistopiclastupdated:Dec11,2014.
INTRODUCTIONPregnancyisaccompaniedbyinsulinresistance,mediatedprimarilybyplacentalsecretionofdiabetogenichormonesincludinggrowthhormone,corticotropinreleasinghormone,placentallactogen,andprogesterone.Theseandothermetabolic
changesensurethatthefetushasanamplesupplyofnutrients.(See"Maternalendocrineandmetabolicadaptationtopregnancy".)
Diabetesdevelopsduringpregnancyinwomenwhosepancreaticfunctionisinsufficienttoovercometheinsulinresistanceassociatedwiththepregnantstate.Amongthemainconsequencesareincreasedrisksofpreeclampsia,macrosomia,andcesareandelivery,
andtheirassociatedmorbidities.
Theapproachtoscreeningforanddiagnosisofdiabetesinpregnantwomenwillbereviewedhere.Managementandprognosisarediscussedseparately:
(See"Gestationaldiabetesmellitus:Glycemiccontrolandmaternalprognosis".)
(See"Gestationaldiabetesmellitus:Obstetricalissuesandmanagement".)
TERMINOLOGYTheterminologyfordescribingdiabetesfirstdiagnosedduringpregnancyvariesamongnationalorganizations.Historically,thetermgestationaldiabeteshasbeendefinedasonsetorfirstrecognitionofabnormalglucosetoleranceduring
pregnancy[1].TheAmericanCollegeofObstetriciansandGynecologists(ACOG)continuestousethisterminology[2].
Inrecentyears,theInternationalAssociationofDiabetesandPregnancyStudyGroup(IADPSG),theAmericanDiabetesAssociation(ADA),theWorldHealthOrganization(WHO),andothershaveattemptedtodistinguishwomenwithprobablepreexistingdiabetes
thatisfirstrecognizedduringpregnancyfromthosewhosediseaseisatransientmanifestationofpregnancyrelatedinsulinresistance[35].Thischangeacknowledgestheincreasingprevalenceofundiagnosedtype2diabetesinnonpregnantwomenofchildbearing
age[6].Theseorganizationstypicallyusethetermgestationaldiabetestodescribediabetesdiagnosedduringthesecondhalfofpregnancy,andtermssuchasovertdiabetesordiabetesmellitusinpregnancytodescribediabetesdiagnosedbystandard
nonpregnantcriteriaearlyinpregnancy,whentheeffectsofinsulinresistancearelessprominent.Thetermgestationaldiabeteshasalsobeenusedtodescribeglucoselevelsinearlypregnancythatdonotmeetstandardnonpregnantcriteriaforovertdiabetesbut
arediagnosticforgestationaldiabetes.
BACKGROUND
PrevalenceTheprevalenceofgestationaldiabetesastraditionallydefinedisabout6to7percentintheUnitedStates(range1to25percent[7])[8].Theprevalencevariesworldwideandamongracialandethnicgroups,generallyinparallelwiththeprevalenceof
type2diabetes.IntheUnitedStates,prevalenceratesarehigherinAfricanAmerican,HispanicAmerican,NativeAmerican,PacificIslander,andSouthorEastAsianwomenthaninwhitewomen[9].Prevalencealsovariesbecauseofdifferencesinscreening
practices,populationcharacteristics(eg,averageageandbodymassindex[BMI]ofpregnantwomen),testingmethod,anddiagnosticcriteria.Prevalencehasbeenincreasingovertime,possiblyduetoincreasesinmeanmaternalageandweight[1016].
In2010,theInternationalAssociationofDiabetesandPregnancyStudyGroup(IADPSG)proposednewscreeninganddiagnosticcriteriafordiabetesinpregnancy[3].Usingthesecriteria,theglobalprevalenceofhyperglycemiainpregnancyhasbeenestimatedat
17percent,withregionalestimatesvaryingbetween10percentinNorthAmericaand25percentinSoutheastAsia[17].
SignificanceSeveraladverseoutcomeshavebeenassociatedwithdiabetesduringpregnancy[1827]:

Preeclampsia
Hydramnios
Macrosomiaandlargeforgestationalageinfant
Fetalorganomegaly(hepatomegaly,cardiomegaly)
Maternalandinfantbirthtrauma
Operativedelivery
Perinatalmortality
Neonatalrespiratoryproblemsandmetaboliccomplications(hypoglycemia,hyperbilirubinemia,hypocalcemia,erythremia)

Importantly,therisksoftheseoutcomesincreaseasmaternalfastingplasmaglucoselevelsincreaseabove75mg/dL(4.2mmol/L)andastheonehourandtwohouroralglucosetolerancetest(GTT)valuesincrease.Thisisacontinuouseffectthereisnoclear
thresholdthatdefinespatientsatincreasedriskofadverseoutcome[19,28].
Inaddition,ifthemotherishyperglycemicduringorganogenesis,suchaswomenwithknownorunknownovertdiabetes,therisksofmiscarriageandcongenitalanomaliesareincreased.(See"Pregestationaldiabetes:Preconceptioncounseling,evaluation,and
management".)

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Longterm,womenwithgestationaldiabetesareatincreasedriskofdevelopingtype2diabetes,aswellastype1diabetesandcardiovasculardisease(see"Gestationaldiabetesmellitus:Glycemiccontrolandmaternalprognosis",sectionon'Longtermrisk').Their
offspringarealsoatriskoflongtermsequelae,suchasobesityandmetabolicsyndrome,whichmaybeattenuatedbymaternaltreatment[27].(See"Infantofadiabeticmother".).
RiskfactorsPregnantwomenwithanyofthefollowingcharacteristicsappeartobeatincreasedriskofdevelopinggestationaldiabetestheriskincreaseswhenmultipleriskfactorsarepresent[29]:
Personalhistoryofimpairedglucosetoleranceorgestationaldiabetesinapreviouspregnancy
Memberofoneofthefollowingethnicgroups,whichhaveahighprevalenceoftype2diabetes:HispanicAmerican,AfricanAmerican,NativeAmerican,SouthorEastAsian,PacificIslander
Familyhistoryofdiabetes,especiallyinfirstdegreerelatives[30]
Prepregnancyweight110percentofidealbodyweightorBMI>30kg/m2,significantweightgaininearlyadulthoodandbetweenpregnancies[31],orexcessivegestationalweightgain[3234]
Maternalage>25yearsofage
Previousdeliveryofababy>9pounds(4.1kg)
Previousunexplainedperinatallossorbirthofamalformedinfant
Maternalbirthweight>9pounds(4.1kg)or<6pounds(2.7kg)
Glycosuriaatthefirstprenatalvisit
Medicalcondition/settingassociatedwithdevelopmentofdiabetes,suchasmetabolicsyndrome,polycysticovarysyndrome(PCOS),currentuseofglucocorticoids,hypertension
Womenatlowriskofgestationaldiabetesareyounger(<25yearsofage),nonHispanicwhite,withnormalBMI(<25kg/m2),nohistoryofpreviousglucoseintoleranceoradversepregnancyoutcomesassociatedwithgestationaldiabetes,andnofirstdegreerelative
withdiabetes[7].Only10percentofthegeneralobstetricpopulationintheUnitedStatesmeetsallofthesecriteriaforlowriskofdevelopinggestationaldiabetes,whichisthebasisforuniversalratherthanselectivescreening(see'Candidatesforscreening/testing'
below)[35].
ApproachesforriskreductionInoverweightandobesewomen,weightlossbeforepregnancycanreducetheriskofdevelopinggestationaldiabetes.However,theefficacyofanexerciseprogramofbriskwalking,stairclimbing,orothervigorousactivity
beforepregnancyandinearlypregnancyforreducingdiabetesriskinallwomenhasnotbeenproven.
WeightlossThepossiblebenefitofweightlossisillustratedbythefollowingtwoexamplesofobservationalstudies:
Inapopulationbasedcohortstudy,obesewomenwholostatleast10pounds(4.5kgs)betweenpregnanciesdecreasedtheirriskofgestationaldiabetesrelativetowomenwhoseweightchangedbylessthan10pounds(relativerisk0.6395%CI0.38
1.02,adjustedforageandweightgainduringeachpregnancy)[36].
Inastudythatcomparedtheincidenceofgestationaldiabetesin346womenwhodeliveredbeforebariatricsurgerywiththeincidencein354womenwhodeliveredafterbariatricsurgery,theincidenceofgestationaldiabeteswaslowerafterbariatric
surgery(8versus27percent,OR0.23,95%CI0.150.36)[37].Bariatricsurgeryalsoinduceshormonalchangesthatmaylowertheriskofgestationaldiabetesindependentofweightloss.
ExerciseInnonpregnantwomen,regularmoderateexerciselowerstheriskofdevelopingtype2diabetescomparedwithbeingsedentary.Althoughobservationalstudieshavereportedanassociationbetweenincreasedphysicalactivityandareducedriskof
gestationaldiabetes,randomizedclinicaltrialshavelargelybeennegative.(See"Preventionoftype2diabetesmellitus",sectionon'Exercise'.)
DatafromobservationalstudiesThevalueofphysicalactivitywasillustratedbya2011metaanalysisincludingsevenprepregnancyandfiveearlypregnancystudies(fiveprospectivecohorts,tworetrospectivecasecontrolstudies,twocrosssectional
studies)[38].Womenwiththehighestnumberofunitsofprepregnancyphysicalactivitybyselfreporthadapproximatelyonehalftheriskofdevelopinggestationaldiabetesaswomenwiththelowestnumberofunits(OR0.45,95%CI0.280.75)unitsof
physicalactivityreflectedfrequency(hoursperweek),energyexpenditure(METhoursperweek),and/orlevelofexertionorintensity.Physicalactivityinearlypregnancywasalsoprotective(OR0.76,95%CI0.700.83).
DatafromrandomizedtrialsIncontrast,a2014metaanalysisofsixrandomizedtrials(n=1089women)foundthatinitiatinganexerciseprogramduringpregnancydidnotsignificantlyreducetheriskofdevelopinggestationaldiabetescomparedwith
routinecare(RR0.91,95%CI0.571.44)[39].Thisanalysiswasdominatedbyonelargetrialof702healthynormalweightwomenwhounderwenta12weekexerciseprogrambeginningrelativelylateinpregnancy(ie,18to22weeksofgestation)[40],
whichmayhaveaccountedforthelackofbenefit.
DietandsmokingInadditiontoexercise,ahealthydietandsmokingcessationarehealthybehaviorsthatmaybeassociatedwithreducedriskofdevelopinggestationaldiabetes[41].Fewstudiesontheroleofdietaryfactorsinthedevelopmentof
gestationaldiabeteshavebeenperformed.Whetheradietlowinredandprocessedmeat,saturatedfat,sugarsweetenedsoda,andrefinedgrainsreducestheriskofdevelopinggestationaldiabetesisunproven[42].However,ahealthydietcanpromoteweight
loss,whichisbeneficial.Smokingcessationshouldbeencouragedinallpatients,andmayreducediabetesrisk.(See"Preventionoftype2diabetesmellitus".)
BENEFITSANDHARMSOFSCREENINGScreeninganddiagnostictestingfordiabetesareperformedbecauseidentifyingpregnantwomenwithdiabetesfollowedbyappropriatetherapycandecreasefetalandmaternalmorbidity,particularlymacrosomia,
shoulderdystocia,andpreeclampsia.(See"Gestationaldiabetesmellitus:Glycemiccontrolandmaternalprognosis",sectionon'Rationalefortreatment'.)
Mostofthecommonlyusedscreeninganddiagnostictestsinvolvedrinkingaglucosecontainingbeveragefollowedbybloodglucosemeasurementnoneofthesetestsareassociatedwithseriousharmfulmaternalorfetaleffects.However,somewomenfindthe
hyperosmolardrinksdifficulttotolerate.Ifgestationaldiabetesisdiagnosed,managementinvolveschangesindiet,anincreasedfrequencyofprenatalvisits,bloodglucosemonitoring,possiblepharmacologictherapy,andadditionalmaternalandfetalmonitoring.
Thecostimplicationsofscreeningversusnotscreeninghavebeenmodeled,andscreeningappearstobecosteffectiveforpreventionoftype2diabetesinpopulationswithahighprevalenceofgestationaldiabetesandtype2diabetes,providedthatlifestyle
interventionsareappliedsubsequenttopregnancy[43].
SCREENINGANDDIAGNOSTICTESTINGThepurposeofscreeningistoidentifyasymptomaticindividualswithahighprobabilityofhavingordevelopingaspecificdisease.Screeningisusuallyperformedasatwostepprocesswheresteponeidentifies
individualsatincreasedriskforthediseasesothatsteptwo,diagnostictesting,whichisdefinitivebutusuallymorecomplicatedorcostlythanthescreeningtest,canbelimitedtotheseindividualsandavoidedinlowriskindividuals.Alternatively,adiagnostictest
canbeadministeredtoallindividuals,whichisaonestepprocess.
Onestepandtwostepapproaches
TwostepapproachThetwostepapproachisthemostwidelyusedapproachforidentifyingpregnantwomenwithgestationaldiabetesintheUnitedStates.Thefirststepisaglucosechallengetest.Screenpositivepatientsgoontothesecondstep,a100

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gram,threehouroralglucosetolerancetest(GTT),whichisthediagnostictestforgestationaldiabetes.
OnestepapproachTheonestepapproachomitsthescreeningtestandsimplifiesdiagnostictestingbyperformingonlya75gram,twohouroralGTT.
Candidatesforscreening/testingIntheUnitedStates,universalscreeningappearstobethemostpracticalapproachbecause90percentofpregnantwomenhaveatleastoneriskfactorforglucoseimpairmentduringpregnancy(see'Riskfactors'above)[35].
Furthermore,2.7to20percentofwomendiagnosedwithgestationaldiabeteshavenoriskfactors[44,45].
Timingofscreening/testingWhiletherearenoprovenbenefitstodiagnosinggestationaldiabetesinearlypregnancy,screeningortestingfordiabetescanbeperformedasearlyasthefirstprenatalvisitifthereisahighdegreeofsuspicionthatthepregnant
womanhasundiagnosedtype2diabetes(eg,bodymassindex[BMI]>30kg/m2,priorhistoryofgestationaldiabetesorknownimpairedglucosemetabolism,polycysticovarysyndrome[PCOS][46])[2].Inparticular,womenwithapriorhistoryofgestational
diabeteshavea33to50percentriskofrecurrence,andsomeoftheserecurrencesmayrepresentunrecognizedintergestationaltype2diabetes.Therearenovalidatedcriteriaforselectinghighriskpregnantwomenforearlyscreening.Riskassessmenttoolsfor
estimatingpersonaldiabetesriskinnonpregnantadultsareavailable[47],butrarelyused.(See"Screeningfortype2diabetesmellitus",sectionon'Calculatingariskscore'.)
Intheabsenceofearlyscreening/testingorifearlyscreening/testingisnegative,universalscreeningisperformedat24to28weeksofgestation[2,4,8].
AsystematicreviewbytheUnitedStatesPreventiveServicesTaskForce(USPSTF)ontheaccuracyofscreeningtestsforgestationaldiabetes,thebenefitsandharmsofscreeningbeforeandafter24weeksofgestation,andthebenefitsandharmsoftreatment,
foundgoodevidencetosupportuniversalscreeningafter24weeks,butnotforuniversalscreeningearlierinpregnancy[8].
ScreeningmethodsLaboratoryscreeningisgenerallyperformedwithaglucosechallengetest.
GlucosechallengetestA50gramoralglucoseloadisgivenwithoutregardtothetimeelapsedsincethelastmealandplasmaglucoseismeasuredonehourlater(GCT,alsosometimescalleda"onehourGTT").Glucoseconcentrationshouldbemeasuredin
venousplasmausinganaccurateandpreciseenzymaticmethod.Thefollowingthresholdshavebeenproposedtodefineapositivescreen:130mg/dL,135mg/dL,or140mg/dL(7.2mmol/L,7.5mmol/L,or7.8mmol/L).
Theoriginalthresholdforanelevatedtest(equivalentto143mg/dL[7.9mmol/L]withcurrentmethodology)wasarbitrary,usedwholebloodandanonspecificglucoseassay,andwasvalidatedbyitsabilitytopredictapositivethreehouroralGTT[48].Useofa
lowerthreshold(130mg/dL[7.2mmol/L]withcurrentmethodology)providesgreatersensitivity,butresultsinmorefalsepositivesandwouldrequireadministeringanoralGTTtomorepatients[49,50].Inasystematicreviewofcohortstudiesofscreeningtestsfor
gestationaldiabetesbytheUSPSTF,atthe130mg/dL(7.2mmol/L)threshold,sensitivityandspecificitywere88to99percentand66to77percent,respectively[51].Atthe140mg/dL(7.8mmol/L)threshold,sensitivitywaslower(70to88percent),butspecificity
washigher(69to89percent).
OthertestsIntheUSPSTFsystematicreviewdescribedabove[51]:
Fastingplasmaglucoselevelatathresholdof85mg/dL(4.7mmol/L)didnotperformaswellasthe50gramglucosechallengetestforidentifyingwomenwhowereultimatelydiagnosedwithgestationaldiabetes.
Nothresholdforglycatedhemoglobin(A1C)inthesecondandthirdtrimestershadbothgoodsensitivityandspecificityasascreeningtestforgestationaldiabetes.Infourstudies,A1Cthresholdsof5.0,5.3,5.5,and7.5wereevaluatedusingdifferent
diagnosticcriteriaforgestationaldiabetes[5255]therewasnoclearpatternbetweenA1Clevelandprobabilityofgestationaldiabetesacrossthefourstudies.
However,inlowresourcesettingswhereuniversalscreeningwithaglucosechallengeordiagnostictestingwithanoralGTTisnotfeasible,useoffastingplasmaglucoseat24to28weekstoscreenwomenmaybeapracticalapproach.Inastudyfrom15Chinese
hospitals,ifperformanceoftheGTTwasrestrictedtowomenwithfastingglucosefrom79mg/dL(4.4mmol/L)to90mg/dL(5.0mmol/L),then50percentofpregnantwomencouldavoidaGTTsince38percentofthispopulationhadfastingglucose<79mg/dL(4.4
mmol/L)and12percenthadfastingglucose>90mg/dL(5.0mmol/L)diagnosticofgestationaldiabetesinthissystem12percentofpatientswithgestationaldiabetesweremissed[56].ThesefindingsmaynotbegeneralizabletootherpopulationssinceAsianshave
ahigherincidenceoftype2diabetesandgestationaldiabetesthanCaucasians,anddifferentdiagnosticthresholdsareusedinChina.
DiagnostictestingmethodsThediagnosisofgestationaldiabetesisbasedonresultsofanoralGTT.However,itshouldbenotedthat,althoughitisalsouniversallyusedtodiagnosediabetesoutsideofpregnancy,thisisanimprecisetestwithpoor
reproducibility[57].AstudythatperformedtwooralthreehourGTTsonetotwoweeksapartin64pregnantwomenwhose50gramglucosechallengewas135mg/dLfound48hadnormal/normal,11hadnormal/abnormal,3hadabnormal/normal,and2had
abnormal/abnormalresults[58].Thus,only50of64(78percent)hadreproducibletestresults.Nevertheless,itisapracticalandwidelyutilizedmeansofdiagnosingbothgestationaldiabetesanddiabetesinnonpregnantindividuals.
TheGTTcanbeperformedasa75gramtwohourtestora100gramthreehourtestthereisnoconsensusregardingtheoptimumthresholdsforapositivetest(table1).Althoughthe100gramthreehourGTTistypicallyperformedasthesecondstepofthetwo
stepapproachwhilethe75gramtwohourtestisperformedastheonlytestintheonestepapproach,thisisarbitrary.Infact,theCanadianDiabetesAssociation(CDA)clinicalguidelinessuggestthe75gramtwohourGTTasthesecondstepofthetwostep
approach[59].Carbohydrateloadingforthreedaysbeforethetesthasbeenrecommended,butisprobablynotnecessaryifthepatientisnotonalowcarbohydratediet[6063].
100gramthreehouroralglucosetolerancetestThe100gramthreehouroralGTTisdiagnosticofgestationaldiabeteswhentwoglucosevaluesareelevated.Themostcommonlyusedthresholdsfordefiningelevatedvalueshavebeenproposedby
CarpenterandCoustanandbytheNationalDiabetesDataGroup(NDDG)(table2)[2,3,49,64,65].BotharemodificationsofthresholdsproposedbyOSullivanandMahan[66],originallybasedonvenouswholebloodsamplesnowconvertedtoplasmasamples.The
CarpenterandCoustanvaluesarelowerbecausethethresholdsderivedfromtheolderSomogyiNelsonmethodofglucoseanalysiswerealsocorrectedtoaccountfortheenzymaticassayscurrentlyisuse.
75gramtwohouroralglucosetolerancetestThe75gramtwohouroralGTTisdiagnosticofgestationaldiabeteswhenoneglucosevalueiselevated.Themostcommonlyusedthresholdsfordefiningelevatedvalueshavebeenproposedbythe
InternationalAssociationofDiabetesandPregnancyStudyGroups(IADPSG)(table3).The75gramtwohouroralGTTismoreconvenient,bettertolerated,andmoresensitiveforidentifyingthepregnancyatriskforadverseoutcomethanthe100gramthreehour
oralGTT.Increasedsensitivityisprimarilyrelatedtothefactthatonlyoneelevatedglucosevalueisneededforapositivetest[67]althoughthecutoffsarealsoslightlylower.
TheIADPSGdefinedthresholdsforthe75gramtwohouroralGTTprimarilybasedonoutcomedatareportedintheHyperglycemiaandAdversePregnancyOutcome(HAPO)study,aprospectiveobservationalstudyofmorethan23,000pregnanciesevaluatedwitha
75gramtwohouroralGTT[3,19].Thesethresholdsrepresenttheglucosevaluesatwhichtheoddsofinfantbirthweight,cordCpeptide(proxyforfetalinsulinlevel),andpercentbodyfat>90percentilewere1.75timestheestimatedoddsoftheseoutcomesat
meanglucoselevels,basedonfullyadjustedlogisticregressionmodels.ComparedtowomenintheHAPOstudywithallglucosevaluesbelowthethresholds,womenwhoexceededoneormoreofthesethresholdshadatwofoldhigherfrequencyoflargefor
gestationalageinfantsandpreeclampsia,and>45percentincreaseinpretermdeliveryandprimarycesareandelivery.Usinganoddsratioof2forthethresholdsdefinedapopulationwithahigherfrequencyoftheseoutcomes,butthedifferencewasmodestand
resultedinfailuretoidentifymanywomenwhowereatalmostcomparablerisk.NodataareavailableontheeffectoftreatingwomendiagnosedwithgestationaldiabetesbyIADPSGcriteriaonpregnancyoutcomes.
PatientsunabletotolerateoralhyperosmolarglucosePeriodicglucoseassessmentisapragmaticapproachforexcludinghyperglycemiainwomenunabletocompleteastandardoralglucosetolerancetest.
SerialglucosemonitoringPeriodicrandomfastingandtwohourpostprandialbloodglucosetestingisamonitoringoptionforwomenathighriskforgestationaldiabeteswhoareunabletotolerateanoralglucoseload.Thisapproachisalsousefulforwomen
whohavedumpingsyndromeafterarouxenYgastricbypassprocedurethesewomenareunlikelytotolerateahyperosmolarglucosesolution[68].(See"Fertilityandpregnancyafterbariatricsurgery".)
FastingplasmaglucoseInasystematicreviewofcohortstudiesofscreeningtestsforgestationaldiabetesperformedfortheUSPSTF,afastingplasmaglucoselevellessthan85mg/dL(4.7mmol/L)by24weeksofgestationperformedwellforidentifying
womenwhodidnothavegestationaldiabetes[51].However,avalueover85mg/dL(4.7mmol/L)performedlesswellthantheoralglucosechallengetestforidentifyingwomenwithgestationaldiabetes.

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TestalternativestotheglucosechallengetestandGTTThehighlyconcentratedhyperosmolarglucosesolutionusedfortheglucosechallengetestandGTTcancausegastricirritation,delayedemptying,andgastrointestinalosmoticimbalance,leadingto
nauseaand,inasmallpercentageofwomen,vomiting[6971].AlternativestotheoralscreeningandGTTshavebeenproposedandarebettertolerated,butappeartobelesssensitiveandhavenotbeenvalidatedinlargestudies.Theseapproachestypically
usecandy,apredefinedmeal,orcommercialsoftdrinksinsteadofastandardglucosemonomerorpolymersolution[7276].NonehavebeenendorsedbytheAmericanDiabetesAssociation(ADA)orAmericanCollegeofObstetriciansandGynecologists
(ACOG).
IntravenousGTTTheintravenousGTTmaybeanalternativeforpatientswhocannottolerateanoralglucoseload[77,78].ThisapproachisrarelyusedandhasnotbeenwellvalidatedagainstoralGTTresultsoragainstpregnancyoutcomehowever,one
author(DC)hasfoundittobeusefulinthesepatients.
IDENTIFICATIONOFOVERTDIABETESINEARLYPREGNANCYAsdiscussedabove(see'Terminology'above),anincreasingproportionofwomenhaveasyetunrecognizedtype2diabetesduetotheincreasingprevalenceofobesityandlackofroutine
glucosescreening/testinginthisagegroup.Identifyingthesewomenearlyinpregnancymaybeimportantbecausetheyareatincreasedriskofhavingachildwithacongenitalanomalyandmaybeatincreasedriskoflongtermcomplicationsfromdiabetes
(nephropathy,retinopathy)[7981].Furthermore,earlyidentificationandtreatmentofhyperglycemiamayreducetheriskofcongenitalanomalies.A2014UnitedStatesPreventiveServicesTaskForce(USPSTF)guidelineconcludedavailableevidencewas
insufficienttoassessthebalanceofbenefitsandharmsofscreeningfordiabetesinasymptomaticpregnantwomenbefore24weeksofgestation[8],whiletheInternationalAssociationofDiabetesandPregnancyStudyGroups(IADPSG)suggestedthatthe
decisiontotestfordiabetesatthefirstprenatalvisitshouldbebaseduponthebackgroundfrequencyofabnormalglucosemetabolisminthepopulationandonlocalcircumstances[3].TheAmericanCollegeofObstetriciansandGynecologists(ACOG)suggests
earlypregnancyscreeningforundiagnosedtype2diabetesinwomenwithriskfactors(eg,previousgestationaldiabetesorknownimpairedglucosemetabolism,obesity)[2].
Severalorganizations(eg,WorldHealthOrganization[WHO],IADPSG,AmericanDiabetesAssociation[ADA],butnotACOG)allowforadiagnosisofovertdiabetesinwomenwhomeetcriteriafordiabetesattheirinitialprenatalvisit.Thegestationalageatwhicha
diagnosisofovertversusgestationaldiabetesislesslikelytobeaccurateisunclear.Statedinanotherway,ifapatientinearlypregnancy(beforesignificantinsulinresistance)meetscriteriafordiabetes,sheisassumedtohavehaddiabetespriortothepregnancy,
butthereisnowaytodetermineatwhatgestationalagethiswouldnolongerbetrue.
ADAcriteriafordiagnosisofdiabetesinnonpregnantadultsmaybeusedtodiagnoseovertdiabetesinearlypregnancy(table4).Thesethresholdswerechosenbecausetheycorrelatewithdevelopmentofadversevasculareventsinnonpregnantindividuals,suchas
retinopathyandcoronaryarterydiseaseovertime.(See"Clinicalpresentationanddiagnosisofdiabetesmellitusinadults".)
RECOMMENDATIONSOFNATIONALORGANIZATIONSManyorganizationshavepublishedrecommendationsforscreeninganddiagnosisofdiabetesinpregnancy,including:
AmericanCollegeofObstetriciansandGynecologists(ACOG,twostepapproach(table5andtable2))[2]
InternationalAssociationofDiabetesandPregnancyStudyGroups(IADPSG,onestepapproach(table3))[3]
AmericanDiabetesAssociation(ADA,onesteportwostepapproach)[4]
WorldHealthOrganization(WHO,onestepapproach(table6))[5]
CanadianDiabetesAssociation(CDA,twostep[preferred]oronestepapproach)[59]
TheEndocrineSociety(onestepapproach)[82]
AustralasianDiabetesinPregnancySociety(WHOapproach)[83]
OURAPPROACHTheauthorsperformuniversaltestingforovertdiabetesattheinitialprenatalvisitbycheckingA1CadiagnosisofovertdiabetesismadewhenA1Cis6.5percent(48mmol/mol)(table4).Giventheincreasingfrequencyoftype2diabetesin
resourcerichcountries,webelieveuniversalearlytestingwhenroutineinitialprenatallaboratorytestsaredrawnisbothdesirableandconvenient,althoughimprovementinpregnancyoutcomehasnotbeenestablishedconclusivelybyrandomizedtrials.Checking
A1Cratherthanfastingglucoseconcentrationisapracticalapproachbecausemostpatientsarenotfastingwhentheirinitialprenatallaboratorytestsaredrawn.However,afastingglucose126mg/dL(7.0mmol/L),ifavailable,isdiagnosticofdiabetes(table4).
(See'Identificationofovertdiabetesinearlypregnancy'above.)
WeacknowledgethatA1Cisnotasuitabletesttodetectmildlyimpairedglucosetolerance.Toidentifypregnantwomenwithmildlyimpairedglucosetolerance,theauthorsperformaglucosetolerancetest(GTT)whenA1Cis5.7to6.4percent(39to46mmol/mol)
atthefirstprenatalvisit.Thisapproachisbasedonthefollowingrationale.ThenormalA1Creferencerangeestablishedinhealthynondiabetic,nonpregnantadultsaged13to39yearsis5.0+/0.5percent(26to37mmol/mol).Inmenandnonpregnantwomen,an
A1C6.5percent(48mmol/mol)isoneofthecriteriausedtodiagnosediabetes(table4).Therefore,anA1C6.5percentearlyinpregnancy,whenA1Clevelsaregenerallyslightlylowerthaninthenonpregnantstate[84],suggestspreviouslyundiagnosedtype2
diabetes.However,anA1Cbelow6.5percentcannotbetakenasstrongevidenceagainstthediagnosisofdiabetes,especiallyinpregnantwomenwithA1Cabovetheupperlimitofthenormalrange.WebelieveexclusionofdiabetesinwomenwithA1Csinthe
rangeassociatedwithanincreasedriskfordiabetes(A1C5.7to6.4percent[39to46mmol/mol])isbestachievedwithanoralGTT[85].Earlyinpregnancy,werecommendusinga75gram,twohouroralGTT(table4).AboutonequarterofwomenwithA1C5.7to
6.4percent(39to46mmol/mol)inearlypregnancydevelopgestationaldiabeteswhenscreenedandtestedlaterinpregnancycomparedwith<10percentofthosewithA1C<5.7percent(39mmol/mol)[86].(See"Clinicalpresentationanddiagnosisofdiabetes
mellitusinadults",sectionon'Diagnosticcriteria'.)
Forwomenwhohavenotbeenpreviouslydiagnosedwithdiabetes,at24to28weeksofgestation,wepreferaonesteptestingapproachusingthe75gramtwohouroralGTTandInternationalAssociationofDiabetesandPregnancyStudyGroups(IADPSG)
thresholdsbecauseofitshighsensitivity(table3).However,mostobstetriciansintheUnitedStatesfollowAmericanCollegeofObstetriciansandGynecologists(ACOG)guidelines,whichsuggestatwostepapproach(50gramoralglucosechallengefollowedby
100gramthreehouroralGTTinscreenpositivewomen)[2].Screeningwithaglucosechallengehasthepracticaladvantagethatitcanbeperformedatanytimeofday,withoutdietarypreparation,whiletheonestepapproachrequiresthatallpatientsundergoan
overnightfastpriortolaboratorytestingandmustbedoneinthemorning.Ontheotherhand,twosteptestinginvolvesanadditionallaboratoryvisitandcollectionoffouradditionalblooddrawsformanywomen[87].
BytheIADPSGestimate,18percentofallpregnantwomenwouldbediagnosedwithgestationaldiabetesusingtheonestepapproachsinceitomitsthescreening50gramglucosechallenge,requiresonlyasingleelevatedvalue,andhasslightlylowerthresholdsfor
apositivetestthanthe100gramthreehouroralGTT(table3andtable2).ACOGandothersrecommendagainstadoptionoftheonestepapproachandcriteriabecauseitwouldincreasetheprevalenceofgestationaldiabetes,leadingtomorefrequentprenatalvisits,
morefetalandmaternalsurveillance,andmoreinterventions,includinginductionoflabor,withoutcleardemonstrationofimprovementsinthemostclinicallyimportanthealthandpatientcenteredoutcomes[87,88].Webelievetheincreaseindiagnosisofgestational
diabeteswouldprovideanopportunitytopreventmacrosomia,preeclampsia,andshoulderdystociaastworandomizedtrialshavedemonstratedthatidentificationandtreatmentofevenmildgestationaldiabetesbyvariouscriteriacanimproveoutcomes[89,90].
Althoughtheincreaseddiagnosisofgestationaldiabeteswouldofferchallengesinuseofresourcesandimprovingtheefficiencyofhealthcaredeliveryforthiscondition,itisnotclearthatincreasedidentificationofpatientswithmildgestationaldiabeteswouldrequire
thesameintensityofglucosemonitoring,fetaltestingandinterventionasthosewithgestationaldiabetesdiagnosedbymorestringentcriteria[91].Inaddition,theincreasedrateofgestationaldiabeteswouldparalleltheincreaseindiabetesandprediabetesinthe
overallpopulation,posingsimilarchallenges.
Whilemoreresearchisnecessary,severalretrospectivestudieshavecomparedpregnancyoutcomewithonestepversustwosteptestingandfoundtheonestepapproachidentifiesmorewomenatincreasedrateofadverseoutcomesassociatedwithdiabetes[92
95].Inaprospectivestudyinwhichthetwostepapproachwasreplacedbytheonestepapproach,theprevalenceofgestationaldiabetesincreased3.5fold,pregnancyoutcomesimprovedsignificantly,andthechangewascosteffective[96].Similarly,amodeling
studyoftheonestepparadigmfordiagnosinggestationaldiabetesfoundittobecosteffectiveintheUnitedStateswhenpostpartuminterventionstopreventtype2diabetesareinitiated[97].Althoughtheonestepapproachappearstobemorecostlythanthetwo

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stepapproach[98],thereissomeevidencethatitiscosteffectiveinimprovingmaternalandneonataloutcomes,evenwhenpostpartuminterventionsarenotincludedincosteffectivenessanalyses[99].
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsandBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgradereadinglevel,andtheyanswerthefouror
fivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmore
detailed.Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingonpatientinfoandthekeyword(s)of
interest.)
Basicstopics(see"Patientinformation:Gestationaldiabetes(diabetesthatstartsduringpregnancy)(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Gestationaldiabetesmellitus(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONSTheterminologyfordiabetesdiagnosedinpregnancyisinflux.Thetermsovertandgestationaldiabetesarebasedprimarilyongestationalageatdiagnosis.Diagnosisofdiabetesat24to28weeksofgestationis
consistentwithgestationaldiabetes,whilediagnosisatthefirstprenatalvisit(inearlypregnancy)ismoreconsistentwithovertdiabetes.(See'Terminology'above.)
OvertdiabetesTheauthorsobtainanA1Clevelattheinitialprenatalvisittoidentifywomenwithovertdiabetesavalue6.5percent(<48mmol/mol)isdiagnostic.Afastingglucose126mg/dL(7.0mmol/L),ifavailable,isalsodiagnosticofdiabetes.IftheA1C
is5.7to6.4percent(39to46mmol/mol),theauthorsperformatwohour75gramoralglucosetolerancetest(GTT)(table4).(See'Ourapproach'above.)However,thereisnoconsensusregardingwhetherorhowtotestfordiabetesatthefirstprenatalvisit.(See
'Identificationofovertdiabetesinearlypregnancy'above.)
Gestationaldiabetes
Identifyingpregnantwomenwithgestationaldiabetesfollowedbyappropriatetherapycandecreasefetalandmaternalmorbidity,particularlymacrosomia,shoulderdystocia,andpreeclampsia.(See'Significance'aboveand'Benefitsandharmsofscreening'
above.)
Weagreewithrecommendationsofmajorsocietiestoscreen/testforgestationaldiabetes(Grade2B).(See'Recommendationsofnationalorganizations'above.)
IntheUnitedStates,universalscreeningappearstobethemostpracticalapproachbecause90percentofpregnantwomenhaveatleastoneriskfactorforglucoseimpairmentduringpregnancy.(See'Candidatesforscreening/testing'above.)
Inwomenwhohavenotbeenpreviouslydiagnosedwithdiabetes,screening/testingforgestationaldiabetesisperformedat24to28weeksofgestationusingaonesteportwostepapproach.(See'Onestepandtwostepapproaches'above.)
Theauthorsrecommendaonesteptestingapproachusingthe75gramtwohouroralGTTandInternationalAssociationofDiabetesandPregnancyStudyGroups(IADPSG)thresholds(table3).(See'Ourapproach'above.)
TheAmericanCollegeofObstetriciansandGynecologists(ACOG)recommendsatwostepapproach(50gramglucosechallengescreenfollowedbya100gramthreehouroralGTT)inscreenpositivepatients(twostepapproach(table5andtable2)).The
AmericanDiabetesAssociation(ADA)supportsuseofeitheraonesteportwostepapproach.(See'Recommendationsofnationalorganizations'aboveand'Screeningmethods'aboveand'Diagnostictestingmethods'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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