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

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 What level to not do diagnostic testing? Often >=200 to diagnose and treat Need to repeat testing at usual time in those with nl early screenWhat level to not do diagnostic testing? Often >=200 to diagnose and treat Need to repeat testing at usual time in those with nl early screen

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

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. Potential risks 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

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

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 U/S- EGA >4500; regular >5000 to offer elective C/SU/S- EGA >4500; regular >5000 to offer elective C/S

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 Start at 32 wks as reasonable time to intervene with C/S and god outcome for infant May lower as technology improvesStart at 32 wks as reasonable time to intervene with C/S and god outcome for infant May lower as technology improves

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 Greatest risk 5yrs postpartum, then plateaus in next 10yrs GDMA1: 50% in 15yrs; GDMA2: 50% in 5yrs v. baseline 7% in 15yrsGreatest risk 5yrs postpartum, then plateaus in next 10yrs GDMA1: 50% in 15yrs; GDMA2: 50% in 5yrs v. baseline 7% in 15yrs

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?