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  • GESTATIONAL DIABETES MELLITUS (GDM) NABEEL S. BONDAGJIMD, FRCSC, FACOGAssociate professorConsultant PerinatologistDepartment of OB/GYN

  • Incidence of GDMApproximate prevalence 3-5%IncreasingIn SA 15-20% diabeticGDM 3-7% Varies with ethnic,race,social habits

  • DIABETES AND PREGNANCY 0.2-0.3% of women of reproductive age have diabetes prior to conception.30% of patients with gestational diabetes develop non-Insulin dependent diabetes later in life


  • What is Gestational Diabetes?Carbohydrate intolerance of varying severity first manifest or diagnosed in pregnancy.

    The definition applies irrespective of the need for insulin treatment and the result of any postnatal glucose tolerance test.

  • Effect of Pregnancy on Diabetes

    Pregnancy is diabetogenicHPL, progesterone antagonize insulinPregnancy causes insulin resistance

  • Maternal Effects of DiabetesMiscarriagePolyhydramniosPreeclampsia (more if diabetic nephropathy)Infection (UTI, candidiasis, chorioamnionitis)Operative delivery (CS rate 50%)

  • Long-term EffectsNephropathyNone if mild-moderateIf severe (creatinine > 0.25 mmol/L), may exacerbate renal failureRetinopathySeems to make it worse

  • Fetal Effects of DiabetesMiscarriageCongenital Malformations 2 - 3 times background rateminimized by good control pre and post-conception.commonest are cardiac defectsCaudal regression (sacral agenesis) Perinatal DeathLate unexplained IUFDperinatal mortality rate doubled

  • Neonatal Effects of Maternal Diabetes (IDM)Macrosomia (40%)Birth trauma shoulder dystociaHypoglycemiaHypocalcaemia/magnesaemiaRespiratory distress syndromeHyperbilirubinaemiaHyperviscosity/ polycythaemiaThe risk of type 1 diabetes mellitus in the child of a woman with the condition is 2%.

  • Risk FactorsBody mass index 25 kg/m2 Family history of type 2 diabetes Age older than 25 yearsMultiparityPrevious gestational diabetes: Macrosomic or large-for-gestational age infant

  • Cont. - Risk FactorsPrevious impaired glucose tolerance with oral glucose tolerance test American Indian or Alaska Native; African American; Asian; Hispanic; Pacific Islander

  • Screening50 gram glucose challenge test at 24-28 weeks7.8mmol or more GTT80% sensitivity 7.2, 90% sensitivityRandom blood sugarnot adequateFasting blood sugarinadequate data

  • Diagnosis

    75g GTTFasting glucose, 75 g load, 2-hour glucoseGDM = fasting 5.5 mmol/L OR 2-hour 8.0 mmol/L

  • Two (2) Abnormal Reading = GDM

  • Treatment of DiabetesType 1:diet, exercise & insulinType 2:diet, exercise:metformin or sulphonylurea alone:metformin and sulphynylurea:metformin, sulphonylurea & thiazolidinedione:insulin


  • Drugs to treat hyperglycemiaInsulin and insulin analogues

    Insulin secretagogues sulphonylurea gliclazide, glibenclamide glyburide. non-sulphonylurea repaglinide, nateglinidelispro insulinaspart insulininsulin glargine

  • Drugs to treat hyperglycemiaInsulin sensitizers biguanide metformin thiazolidinedione rosiglitazone, pioglitazoneIntestinal absorption inhibitorsacarboseorlistat

  • TEXT BOOKS TEACHINGOral hypoglycemia are contraindicated in pregnancy

    Risk of fetal anomalies

    Risk of neonatal hypoglycemiaIncreasing risk of PET

  • ACOG/ADAInsulin and its analogues are the only agents to be used in pregnancySOGS !!!!!!!!!


    No evident that it causes fetal hypoglycemia 3 cases studies.

    No strong evidence it cause congenital anomalies.

  • EvidenceEarly reports

    Oral hypoglycemic Fetal congenital anomaliesCritical review of old data suggested that thedescribed reports associated with fetal anomaliesare most likely related to hyperglycemia

    Poor control prior to pregnancy diabeticemberyopathy

  • Elliot et al (American Journal of Obstetrics & Gynecology 1991).

    Elliot et al (American Journal of Obstetrics & Gynecology 1994) proved in Lab. that Glyburide does not cross the placenta in significant amounts (in human placental modules).

  • Perfusion studies of glyburide transfer across thehuman placenta: Implications for fetal safetyJennifer Kraemer, MSc, Julia Klein, MSc, Angelica Lubetsky,Am j Ob& Gyne 2006The objective of study was to document, using a human placenta perfusion model, whether glyburide is actively effluxed from the fetal to the maternal circulation.

    Conclusion: these experiments suggest that glyburide is actively efflux by a transporter from the maternal to fetal site

  • Coetzee etall (South African MJ 1984)

    Oral hypoglycemic in the first trimester and fetaloutcome Patients retrospective review78 used OHA93 notNo significant difference in the outcomeComparable results in blood sugar control

  • The safety of oral hypoglycemic agents in the first trimester of pregnancy :a meta-analysisGutzin ea alCan J Clinical Pharm 2003OBJECTIVE: To examine the relationship between first trimester exposure to oral hypoglycemic agents and ,fetal congenital anomalies and neonatal morbidity.METHODS: a systematic review and meta-analysis of all studies that was reported on women exposed to OHGA in the first trimester

  • Gulzin etalCan J. Clin. Pharmacology (2003)Meta-analysis on the safety of OHA inthe first trimester/University of Toronto 10 studies fulfilled the criteriaResults In all studies No difference in major anomalies among Exposed Vs non exposed fetuses

  • RESULTS: Ten studies met the inclusion criteria -There was no significant difference in the rate of congenital anomalies betweenexposed and non exposed-No difference in the neonatal deathConclusions:First trimester exposure to OHA did not increase the rate of congenital anomalies nor the neonatal deathFurther studies needed do document the safety and the glycemic control

  • Safety of glyburide for gestational diabetes:a meta-analysis of pregnancy outcomesMoretti ME, Rezvani M, Koren G.Ann Pharmacotherapy. 2008 Apr OBJECTIVE: To determine the safety of glyburide use in pregnancy in the treatment of gestational diabetes compared with insulin therapy by analyzing all available human studies.METHODS: a systematic review and meta-analysis of all randomized and cohort studies that reported on the perinatal complications among women with gestational diabetes who received glyburide versus insulin

  • RESULTS: Nine studies met the inclusion criteria, including a total of 745 glyburide exposed pregnancies and 637 insulin-exposed pregnancies CONCLUSIONS: The data do not suggest increased perinatal risks with glyburide. The effectiveness and safety of glyburide require further evaluation, as most studies to date were not randomized

  • Comparison of Glyburide and insulin for the management of gestational diabetes in a large managed care organization(American j Obstet Gynecol 2005)

    Jacobson GF A retrospective study268 insulin 1999-2000

    236 glyburide 2001-2002

  • Conclusions:

    No difference in glycemic control birthweight NN outcomeSlight increase in PET + phototherapyNeed for glyburide group

  • A comparison of glyburide and insulin in women with gestational diabetes mellitus.Department of Obstetrics and Gynecology, St. Lukes-Roosevelt Hospital Center, New York 10019, USA. Olanger@slrhc.orgLanger O, Conway DL, Berkus MD, Xenakis EM, Gonzales O.N Engl J Med. 2000 Oct. 19;343(16):1178-9

  • 404 women randomized11 33 weeks

    Group I Glyburide201

    Group II insulin 203

  • ResultsNo difference in the glucose blood level.

    No difference in congenital anomalies.

    No difference in the birth weight.

    Glyburide was not detected in the cord blood of any of the fetuses of the glyburide group.

  • There were no significant differences between the glyburide and insulin groups in lung complications (8 percent and 6 percenthypoglycemia (9 percent and 6 percentwho were admitted to a neonatal intensive care unit (6 percent and 7 percent

  • ConclusionIn women with GDM, Glyburide is clinically effective alternative to insulin.

  • Langer O. Am. J. Obst. & Gynecol ,2005 JInsulin and glyburide therapy: dosage, severitylevel of gestational diabetes , and pregnancyoutcomeSecondary analysis of the trialConclusion:Glyburide and insulin are equally efficient forTreatment of GDM at all level of severity

  • In PCO patientsMetformin use in the first trimester does not increase M C AGlueck et all ( pilot study) continues metformin through out pregnancy in women with PCOSafe and decrease first trimester abortion(Fertility & sterility 2001)

  • Glueck etall (human reproduction 2004)

    Follow up of 126 infants born for PCOwomen on continuous metformin throughout pregnancyConclusion:Decrease GDM does not cause any adverseeffects on babies up to 4 year follow up

  • Jakubaurez et all

    Effect of Metformin in early pregnancy loss in PCO

    (J. Of Clinical endocrinology & Metabolism 2002)


  • Metformin Therapy Throughout Pregnancy Reduces GDMetformin Helps Prevent Gestational DiabetesMetformin Shows Promise in Preventing MiscarriageWait for the MIG TRIAL 2007 ?

  • First Visit Routine management PLUS Counseling Urinary protein Ophthalmoscopy each trimester Glycaemic control Organize fetal surveillance

  • Blood sugar control and the prevention of the complication of D.M.Blood sugar control 100mg


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