Gestational Diabetes Review & Advances in Treatment

1. Gestational DiabetesReview & Advances in Treatment Virginia Underwood, Capt, USAF, MC Family Practice Resident David Grant Medical Center

2. Overview • Definition • Screening • Conventional Treatments • New Treatments • Goals • Postpartum Screening

3. Questions • Does screening for and treating GDM affect infant or maternal morbidity or mortality? • Does antepartum fetal testing prevent stillbirth or infant morbidity? • Does postpartum glucose tolerance testing have an appreciable long term impact on women with a history of GDM?

4. Epidemiology • 3-7% of pregnant women in the U.S. • Increasing prevalence • Risk factors: • >25 yrs • Hispanic, Native American, South or East Asian, Pacific Islands, African American • BMI >25 • Previous history glucose intolerance • History obstetric outcomes associated with GDM • History diabetes in a first degree relative

5. Question #1 Does screening for and treating GDM affect infant or maternal morbidity or mortality?

6. GDM Criteria *2 or more criteria met = positive diagnosis (cutoff points in mg/dl) † 1 or more criteria met = positive diagnosis

7. Screening & Diagnosis • Screen: 50g glucose 1 hour glucose challenge • non-fasting state (higher or similar values with fast) • Diagnosis: 100g, 3 hour glucose tolerance test • Positive test = 2 or more thresholds met/exceeded • No smoking prior • Unrestricted diet: at least 150g carbohydrates/d for at least 3 days prior (to avoid spurious high values) • One abnormal value with increased risk for macrosomic infants & associated morbidities

8. When to Screen? • 24-28 weeks gestation • Early screening: • marked obesity • personal history of GDM (33-50% likelihood recurrence) • glycosuria • strong family history of diabetes

9. Maternal glucose intolerance Adverse pregnancy outcomes

10. Recommendations • USPSTF: “evidence is insufficient to recommend for or against routine screeening.” (did find fair - good evidence that screening for GDM and treatment of hyperglycemia could reduce the frequency of fetal macrosomia) • ADA: officially recommends screening for GDM, but may omit low risk women • ACOG: universal screening is the most sensitive approach; screening may be omitted in low risk women, but universal screening as more practical approach

11. Treatment Questions • Does GDM pose serious risks to offspring? • Does treatment reduce those risks? • Does treatment reduce other risks associated with GDM (obesity/diabetes in offspring)? • Does reducing glycemia reduce risks? (macrosomia & cesarean delivery)

12. Macrosomia Brachial plexus injury Fracture with delivery Fetal hypoglycemia Fetal hyperbilirubinemia Fetal hypocalcemia Childhood obesity Neuropsychological outcomes Development of diabetes Perinatal mortality 3rd/4th degree lacerations Instrument deliveries Cesarean delivery Preeclampsia Future diabetes mellitus Potential risks

13. Confounding Factors • Fetal size: maternal glucose levels, maternal BMI, pregnancy weight gain, parity • Spectrum of sugars of normal to diabetic patients (single abnormal value of 3hGTT  large for gestational infants) • Normal pregnancies with very narrow glucose range (euglycemia difficult to achieve) • Alerting physicians to increased risk

14. Confounding Factors • Large number of subjects needed • 450 infants undergoing cesarean delivery to prevent one permanent brachial plexus injury • Lowered cesarean delivery threshold: resulting morbidity and costs outweigh benefits?

15. Research-Crowther et al. • Multicenter, 1000 women • 75g oral glucose tolerance test between 24-32 weeks gestation • Subjects: below 140 fasting, and between 140-198 at 2 hours after glucose challenge • Intervention: glucose monitoring, dietary counseling/insulin to maintain sugars • Goals: premeal/fasting <99 and 2h postprandial <126 • Control: routine care where GDM screening not standard

16. Crowther et al. Results • Intervention group with reduced: • Perinatal death (5 v. 0) • Shoulder dystocia • Bone fracture • Nerve palsy • Macrosomia (≥4kg: 21% v. 10%) • Postpartum depression (health status)

17. Crowther et al. Results • Cesarean delivery rates similar between groups • Control group with reduced: • Inductions of labor • Admissions to neonatal intensive care unit

18. Research- Langer et al. • 555 gestational diabetics diagnosed after 37 weeks v. 1110 subjects treated for gestational diabetes mellitus and 1110 nondiabetic subjects • Adverse outcomes: 59% for untreated, 18% for treated, and 11% for nondiabetic • 2- to 4-fold increase in metabolic complications and macrosomia/LGA in the untreated group & no difference between nondiabetic and treated Increasing evidence that identifying women with GDM is important because appropriate therapy can decrease fetal and maternal morbidity, particularly macrosomia

19. Upcoming studies • Maternal-Fetal Medicine Network multicenter trial of treatment of mild GDM • HAPO- Hyperglycemia and Adverse Pregnancy Outcome study

20. Treatment Recommendations • American Diabetes Association: • Nutrition counseling • Carbohydrates: 35-40% of daily calories • (caution for ketosis  IQ/psychomotor development) • BMI >30kg/m2: lowering daily calories by 30% (goal 25kcal/kg actual weight per day)

21. Treatment Recommendations • Trial 2 weeks (if initial fasting <95) • Initial fasting >95 unlikely to be controlled • Exercise: • Weight reduction and improve glucose metabolism • Effects on fasting glucose/tolerance & macrosomia

22. Glucose goals • Fasting <90-105 • 1h <130-140 • 2h <120 • 38% with initial fasting glucose <95 required insulin for optimal control • 70% with initial fasting glucose 95-104

23. Monitoring • Frequency not established • Reduces?: • Perinatal mortality/hypoglycemia/shoulder dystocia • Macrosomia • Timing: • Fasting v. postprandial (nadirs v. glucose excesses) • 1h v. 2h postprandial • Severe/preexistent v. mild  frequency

24. Insulin • When: • > 95 or 105 fasting • >120 2 h postprandial • Initial dose: 0.7U/kg/day • AM 2/3  2/3 NPH, 1/3 Reg • PM 1/3  1/2 NPH, 1/2 Reg • *once daily ultralente with very short acting lispro insulin

25. Oral hypoglycemics • Previous concerns: (Diabinese & Orinase) • 1st generation sulfonylureas • Potential teratogenicity • Transport across placenta (hypoglycemia) • Glyburide: • 2nd generation sulfonylurea • Does not enter fetal circulation (in vitro/vivo) • Comparable maternal/neonatal outcomes • Less maternal hypoglycemia • Metformin (PCOS, gestational diabetes, first trimester miscarriage rates)

26. Glyburide • Start: 2.5 mg once or twice daily • Increase: by 2.5 mg to 5 mg at weekly intervals as needed until maximum dose of 20 mg daily • Peak plasma level of glyburide: 2–4 hours after administration • Timing administration with hyperglycemia (daytime/fasting) • Fasting hyperglycemia on diet: higher dose/bid • 5-20% conversion to insulin *fasting plasma glucose <110 & no sulfa allergy

27. Question #2 Does antepartum fetal testing prevent stillbirth or infant morbidity?

28. Antepartum Fetal Testing • Purpose: identify patients at risk for stillbirth • Stillbirth rare occurrence • Practice patterns: starting at 32-40 weeks gestation • ACOG: • Glucose not well controlled • Requiring insulin • Concomitant hypertension • NST/AFI, full biophysical profile • No evidence regarding fetal ultrasound  macrosomia Insufficient evidence regarding impact of antenatal fetal testing on stillbirth rate, and neonatal morbidity

29. Question #3 Does postpartum glucose tolerance testing have an appreciable long term impact on women with a history of GDM?

30. Postpartum screening • 50% women with GDM developing diabetes mellitus in a 28yr study (v. 7% of controls) • Possible preexistent diabetes • 6-8wks postpartum • 2h OGTT (75g) • Impaired: 140-199 (100-125) • DM: ≥ 200 (≥ 126) • Diet, exercise, weight reduction counseling No long-term follow-up studies that verify the benefit of postpartum diagnostic testing

31. Summary • Definition • Screening • Conventional Treatments • New Treatments • Goals • Postpartum Screening

32. Bibliography • 1. Langer O, Conway DL, Berkus MD, Xenakis EM-J, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. NEJM 2000;343:1134–8. • 2. Saade, George. Gestational Diabetes Mellitus: A Pill or a Shot?. Obstetrics & Gynecology 2005; 105:456-7. • 3. Turok d, Ratcliffe S, Baxley E. Management of gestational diabetes mellitus. American Family Physician 2003; 68: 1767-1772. • 4. Greene M, Solomom C. Gestational diabetes mellitus – time to treat. NEJM 2005; 352: 2544-2546. • 5. Crowther C, Hiller J, Moss J, McPhee A, Jeffries W, Robinson J. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. NEJM 2005; 352: 2477-2486. • 6. Kjos S, Buchanan T. Gestational Diabetes Mellitus – current concepts. NEJM 1999; 341: 1749-1756. • 7. Naylor C, Phil D, Sermer M, Chen E, Farine D. Selective screening for gestational diabetes mellitus. NEJM 1997; 337: 1591-1597. • 8. Caughey A. Management of Diabetes in Pregnancy. Johns Hopkins Advanced Studies in Medicine 2006: 309-318. • 9. Gestational Diabetes. ACOG Practice Bulletin. 2006: 518-531.

33. Questions? Sugar-free chocolate mousse cake