Underwood - GDM

8/9/2019 Underwood - GDM

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Gestational DiabetesGestational DiabetesReview & Advances in TreatmentReview & Advances in Treatment

Virginia Underwood, Capt, USAF, MCVirginia Underwood, Capt, USAF, MC

Family Practice ResidentFamily Practice ResidentDavid Grant Medical CenterDavid Grant Medical Center


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OverviewOverview

DefinitionDefinition

ScreeningScreening

Conventional TreatmentsConventional Treatments New TreatmentsNew Treatments

GoalsGoals

Postpartum ScreeningPostpartum Screening


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QuestionsQuestions

Does screening for and treating GDM affectDoes screening for and treating GDM affect

infant or maternal morbidity or mortality?infant or maternal morbidity or mortality?

Does antepartum fetal testing prevent stillbirthDoes antepartum fetal testing prevent stillbirthor infant morbidity?or infant morbidity?

Does postpartum glucose tolerance testing haveDoes postpartum glucose tolerance testing have

an appreciable long term impact on women withan appreciable long term impact on women with

a history of GDM?a history of GDM?


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EpidemiologyEpidemiology

33--7% of pregnant women in the U.S.7% of pregnant women in the U.S.

Increasing prevalenceIncreasing prevalence

Risk factors:Risk factors: >25 yrs>25 yrs

Hispanic, Native American, South or East Asian, PacificHispanic, Native American, South or East Asian, PacificIslands, African AmericanIslands, African American

BMI >25BMI >25

Previous history glucose intolerancePrevious history glucose intolerance History obstetric outcomes associated with GDMHistory obstetric outcomes associated with GDM

History diabetes in a first degree relativeHistory diabetes in a first degree relative


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Question #1

Question #1

Does screening for and treating GDMDoes screening for and treating GDM

affect infant or maternal morbidity oraffect infant or maternal morbidity ormortality?mortality?


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GDM CriteriaGDM Criteria

NationalNational

Diabetes DataDiabetes Data

Group*Group*

AmericanAmerican

DiabetesDiabetes

Association*Association*

World healthWorld health

OrganizationOrganization

Carpenter andCarpenter and

Coustan*Coustan*

FastingFasting 105105 9595 126 126 9595

1 hour1 hour 190190 180180 -- 180180

2 hours2 hours 165165 155155 140 140 155155

3 hours3 hours 145145 140140 -- 140140

*2 or more criteria met = positive diagnosis (cutoff points inmg/dl)

=


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Screening & DiagnosisScreening & Diagnosis

Screen: 50g glucose 1 hour glucose challengeScreen: 50g glucose 1 hour glucose challenge nonnon--fasting state (higher or similar values with fast)fasting state (higher or similar values with fast)

Diagnosis: 100g,3

hour glucose tolerance testDiagnosis: 100g,3

hour glucose tolerance test Positive test = 2 or more thresholds met/exceededPositive test = 2 or more thresholds met/exceeded

No smoking priorNo smoking prior

Unrestricted diet: at least 150g carbohydrates/d forUnrestricted diet: at least 150g carbohydrates/d for

at least 3 days prior (to avoid spurious high values)at least 3 days prior (to avoid spurious high values) One abnormal value with increased risk forOne abnormal value with increased risk for

macrosomic infants & associated morbiditiesmacrosomic infants & associated morbidities


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When to Screen?When to Screen?

2424--28 weeks gestation28 weeks gestation

Early screening:Early screening:

marked obesitymarked obesity personal history of GDM (33personal history of GDM (33--50% likelihood50% likelihood

recurrence)recurrence)

glycosuriaglycosuria

strong family history of diabetesstrong family history of diabetes


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Maternal glucoseintolerance

Adverse pregnancyoutcomes


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RecommendationsRecommendations

USPSTF: evidence is insufficient to recommend for orUSPSTF: evidence is insufficient to recommend for oragainst routine screeening. (did find fairagainst routine screeening. (did find fair -- goodgoodevidence that screening for GDM and treatment ofevidence that screening for GDM and treatment of

hyperglycemia could reduce the frequency of fetalhyperglycemia could reduce the frequency of fetalmacrosomia)macrosomia)

ADA: officially recommends screening for GDM, butADA: officially recommends screening for GDM, butmay omit low risk womenmay omit low risk women

ACOG: universal screening is the most sensitiveACOG: universal screening is the most sensitiveapproach; screening may be omitted in low risk women,approach; screening may be omitted in low risk women,but universal screening as more practical approachbut universal screening as more practical approach


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Treatment QuestionsTreatment Questions

Does GDM pose serious risks to offspring?Does GDM pose serious risks to offspring?

Does treatment reduce those risks?Does treatment reduce those risks?

Does treatment reduce other risks associatedDoes treatment reduce other risks associatedwith GDM (obesity/diabetes in offspring)?with GDM (obesity/diabetes in offspring)?

Does reducing glycemia reduce risks?Does reducing glycemia reduce risks?

(macrosomia & cesarean delivery)(macrosomia & cesarean delivery)


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Potential risksPotential risks

MacrosomiaMacrosomia

Brachial plexus injuryBrachial plexus injury

Fracture with deliveryFracture with delivery

Fetal hypoglycemiaFetal hypoglycemia

Fetal hyperbilirubinemiaFetal hyperbilirubinemia

Fetal hypocalcemiaFetal hypocalcemia

Childhood obesityChildhood obesity

NeuropsychologicalNeuropsychologicaloutcomesoutcomes

Development of diabetesDevelopment of diabetes

Perinatal mortalityPerinatal mortality

33rdrd/4/4thth degree lacerationsdegree lacerations

Instrument deliveriesInstrument deliveries

Cesarean deliveryCesarean delivery

PreeclampsiaPreeclampsia

Future diabetes mellitusFuture diabetes mellitus


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Confounding FactorsConfounding Factors

Fetal size: maternal glucose levels, maternalFetal size: maternal glucose levels, maternal

BMI, pregnancy weight gain, parityBMI, pregnancy weight gain, parity

Spectrum of sugars of normal to diabeticSpectrum of sugars of normal to diabeticpatients (single abnormal value of3hGTTpatients (single abnormal value of3hGTT large for gestational infants)large for gestational infants)

Normal pregnancies with very narrow glucoseNormal pregnancies with very narrow glucose

range (euglycemia difficult to achieve)range (euglycemia difficult to achieve)

Alerting physicians to increased riskAlerting physicians to increased risk


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Confounding FactorsConfounding Factors

Large number of subjects neededLarge number of subjects needed

450 infants undergoing cesarean delivery to450 infants undergoing cesarean delivery to

prevent one permanent brachial plexus injuryprevent one permanent brachial plexus injury Lowered cesarean delivery threshold: resultingLowered cesarean delivery threshold: resulting

morbidity and costs outweigh benefits?morbidity and costs outweigh benefits?


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ResearchResearch--Crowther et al.Crowther et al.

Multicenter, 1000 womenMulticenter, 1000 women

75g oral glucose tolerance test between 2475g oral glucose tolerance test between 24--32 weeks32 weeksgestationgestation

Subjects: below 140 fasting, and between 140Subjects: below 140 fasting, and between 140--198 at 2198 at 2hours after glucose challengehours after glucose challenge

Intervention: glucose monitoring, dietaryIntervention: glucose monitoring, dietarycounseling/insulin to maintain sugarscounseling/insulin to maintain sugars

Goals: premeal/fasting


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Crowther et al. ResultsCrowther et al. Results

Intervention group with reduced:Intervention group with reduced:

Perinatal death (5 v. 0)Perinatal death (5 v. 0)

Shoulder dystociaShoulder dystocia Bone fractureBone fracture

Nerve palsyNerve palsy

Macrosomia (4kg: 21% v. 10%)Macrosomia (4kg: 21% v. 10%)

Postpartum depression (health status)Postpartum depression (health status)


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Crowther et al. ResultsCrowther et al. Results

Cesarean delivery rates similar between groupsCesarean delivery rates similar between groups

Control group with reduced:Control group with reduced:

Inductions of laborInductions of laborAdmissions to neonatal intensive care unitAdmissions to neonatal intensive care unit


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ResearchResearch-- Langer et al.Langer et al.

555 gestational diabetics diagnosed after 37555 gestational diabetics diagnosed after 37

weeks v. 1110 subjects treated for gestationalweeks v. 1110 subjects treated for gestationaldiabetes mellitus and 1110 nondiabetic subjectsdiabetes mellitus and 1110 nondiabetic subjects

Adverse outcomes: 59% for untreated, 18% forAdverse outcomes: 59% for untreated, 18% fortreated, and 11% for nondiabetictreated, and 11% for nondiabetic

22-- to 4to 4--fold increase in metabolic complicationsfold increase in metabolic complications

and macrosomia/LGA in the untreated group &and macrosomia/LGA in the untreated group &no difference between nondiabetic and treatedno difference between nondiabetic and treated

Increasing evidence that identifying women

with GDM is important because appropriatetherapy can decrease fetal and maternalmorbidity, particularly macrosomia


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Upcoming studiesUpcoming studies

MaternalMaternal--Fetal Medicine Network multicenterFetal Medicine Network multicenter

trial of treatment of mild GDMtrial of treatment of mild GDM

HAPOHAPO-- Hyperglycemia and Adverse PregnancyHyperglycemia and Adverse PregnancyOutcome studyOutcome study


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Treatment RecommendationsTreatment Recommendations

American Diabetes Association:American Diabetes Association:

Nutrition counselingNutrition counseling

Carbohydrates: 35Carbohydrates: 35--40% of daily calories40% of daily calories (caution for ketosis(caution for ketosis IQ/psychomotorIQ/psychomotor

development)development)

BMI >30kg/mBMI >30kg/m22: lowering daily calories by30% (goal: lowering daily calories by30% (goal

25kcal/kg actual weight per day)25kcal/kg actual weight per day)


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Treatment RecommendationsTreatment Recommendations

Trial 2 weeks (if initial fasting 95 unlikely to be controlled

Exercise:Exercise:Weight reduction and improve glucose metabolismWeight reduction and improve glucose metabolism

Effects on fasting glucose/tolerance & macrosomiaEffects on fasting glucose/tolerance & macrosomia


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Glucose goalsGlucose goals

Fasting


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MonitoringMonitoring

Frequency not establishedFrequency not established

Reduces?:Reduces?:

Perinatal mortality/hypoglycemia/shoulder dystociaPerinatal mortality/hypoglycemia/shoulder dystocia MacrosomiaMacrosomia

Timing:Timing:

Fasting v. postprandial (nadirs v. glucose excesses)Fasting v. postprandial (nadirs v. glucose excesses)

1h v. 2h postprandial1h v. 2h postprandial

Severe/preexistent v. mildSevere/preexistent v. mild frequencyfrequency


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InsulinInsulin

When:When:

> 95 or 105 fasting> 95 or 105 fasting

>120 2 h postprandial>120 2 h postprandial Initial dose: 0.7U/kg/dayInitial dose: 0.7U/kg/day

AM 2/3AM 2/3 2/3 NPH, 1/3 Reg2/3 NPH, 1/3 Reg

PM 1/3PM 1/3

1/2 NPH, 1/2 Reg1/2 NPH, 1/2 Reg *once daily ultralente with very short acting*once daily ultralente with very short acting

lispro insulinlispro insulin


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Oral hypoglycemicsOral hypoglycemics

Previous concerns: (Diabinese & Orinase)Previous concerns: (Diabinese & Orinase) 11stst generation sulfonylureasgeneration sulfonylureas

Potential teratogenicityPotential teratogenicity

Transport across placenta (hypoglycemia)Transport across placenta (hypoglycemia)

Glyburide:Glyburide: 22ndnd generation sulfonylureageneration sulfonylurea

Does not enter fetal circulation (in vitro/vivo)Does not enter fetal circulation (in vitro/vivo)

Comparable maternal/neonatal outcomesComparable maternal/neonatal outcomes

Less maternal hypoglycemiaLess maternal hypoglycemia Metformin (PCOS, gestational diabetes, first trimesterMetformin (PCOS, gestational diabetes, first trimester

miscarriage rates)miscarriage rates)


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GlyburideGlyburide

Start: 2.5 mg once or twice dailyStart: 2.5 mg once or twice daily

Increase: by 2.5 mg to 5 mg at weekly intervals asIncrease: by 2.5 mg to 5 mg at weekly intervals asneeded until maximum dose of 20 mg dailyneeded until maximum dose of 20 mg daily

Peak plasma level of glyburide: 2Peak plasma level of glyburide: 24 hours after4 hours afteradministrationadministration

Timing administration with hyperglycemiaTiming administration with hyperglycemia(daytime/fasting)(daytime/fasting)

Fasting hyperglycemia on diet: higher dose/bidFasting hyperglycemia on diet: higher dose/bid 55--20% conversion to insulin20% conversion to insulin

*fasting plasma glucose


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Question #2

Question #2

Does antepartum fetal testing preventDoes antepartum fetal testing prevent

stillbirth or infant morbidity?stillbirth or infant morbidity?


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Antepartum Fetal TestingAntepartum Fetal Testing

Purpose: identify patients at risk for stillbirthPurpose: identify patients at risk for stillbirth

Stillbirth rare occurrenceStillbirth rare occurrence

Practice patterns: starting at 32Practice patterns: starting at 32--40 weeks gestation40 weeks gestation

ACOG:ACOG:

Glucose not well controlledGlucose not well controlled

Requiring insulinRequiring insulin

Concomitant hypertensionConcomitant hypertension NST/AFI, full biophysical profileNST/AFI, full biophysical profile

No evidence regarding fetal ultrasoundNo evidence regarding fetal ultrasound macrosomiamacrosomia

Insufficient evidence regardingimpact of antenatal fetal testing on

stillbirth rate, and neonatal

morbidity


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Question #3Question #3

Does postpartum glucose tolerance testingDoes postpartum glucose tolerance testinghave an appreciable long term impact onhave an appreciable long term impact on

women with a history of GDM?women with a history of GDM?


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Postpartum screeningPostpartum screening

50% women with GDM developing diabetes50% women with GDM developing diabetes

mellitus in a 28yr study (v. 7% of controls)mellitus in a 28yr study (v. 7% of controls)

Possible preexistent diabetesPossible preexistent diabetes 66--8wks postpartum8wks postpartum

2h OGTT (75g)2h OGTT (75g)

Impaired: 140Impaired: 140--199 (100199 (100--125)125)

DM: 200 ( 126)DM: 200 ( 126)

Diet, exercise, weight reduction counselingDiet, exercise, weight reduction counseling

No long-term follow-up studies thatverify the benefit of postpartum

diagnostic testing


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SummarySummary

DefinitionDefinition

ScreeningScreening

Conventional TreatmentsConventional Treatments New TreatmentsNew Treatments

GoalsGoals

Postpartum ScreeningPostpartum Screening


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BibliographyBibliography

1. Langer O, Conway DL, Berkus MD, Xenakis EM1. Langer O, Conway DL, Berkus MD, Xenakis EM--J, Gonzales O. A comparison of glyburideJ, Gonzales O. A comparison of glyburideand insulin in women with gestational diabetes mellitus. NEJM 2000;343:1134and insulin in women with gestational diabetes mellitus. NEJM 2000;343:11348.8.

2. Saade, George. Gestational Diabetes Mellitus: A Pill or a Shot?. Obstetrics & Gynecology2. Saade, George. Gestational Diabetes Mellitus: A Pill or a Shot?. Obstetrics & Gynecology2005; 105:4562005; 105:456--7.7.

3. Turok d, Ratcliffe S, Baxley E. Management of gestational diabetes mellitus. American Family3. Turok d, Ratcliffe S, Baxley E. Management of gestational diabetes mellitus. American FamilyPhysician 2003; 68: 1767Physician 2003; 68: 1767--1772.1772.

4. Greene M, Solomom C. Gestational diabetes mellitus4. Greene M, Solomom C. Gestational diabetes mellitus time to treat. NEJM 2005; 352: 2544time to treat. NEJM 2005; 352: 2544--2546.2546. 5. Crowther C, Hiller J, MossJ, McPhee A, Jeffries W, RobinsonJ. Effect of treatment of5. Crowther C, Hiller J, MossJ, McPhee A, Jeffries W, RobinsonJ. Effect of treatment of

gestational diabetes mellitus on pregnancy outcomes. NEJM 2005; 352: 2477gestational diabetes mellitus on pregnancy outcomes. NEJM 2005; 352: 2477--2486.2486. 6. Kjos S, Buchanan T. Gestational Diabetes Mellitus6. Kjos S, Buchanan T. Gestational Diabetes Mellitus current concepts. NEJM 1999; 341:current concepts. NEJM 1999; 341:

17491749--1756.1756. 7. Naylor C, Phil D, Sermer M, Chen E, Farine D. Selective screening for gestational diabetes7. Naylor C, Phil D, Sermer M, Chen E, Farine D. Selective screening for gestational diabetes

mellitus. NEJM 1997; 337: 1591mellitus. NEJM 1997; 337: 1591--1597.1597.

8. Caughey A. Management of Diabetes in Pregnancy. Johns Hopkins Advanced Studies in8. Caughey A. Management of Diabetes in Pregnancy. Johns Hopkins Advanced Studies inMedicine 2006: 309Medicine 2006: 309--318.318. 9. Gestational Diabetes. ACOG Practice Bulletin. 2006: 5189. Gestational Diabetes. ACOG Practice Bulletin. 2006: 518--531.531.


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Questions?Questions?

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