1. Preconception Care and Management of Gestational Diabetes Mahmud Rajabalee M.B.BCh (Ainshams, Cairo) DIS (France)

2. Learning objectives To realize the importance of preconception care of women with diabetes to prevent adverse pregnancy outcomes To describe how to achieve optimal glycemic control in the preconception period and throughout pregnancy To point out the need for postpartum follow- up of patients with gestational diabetes

3. Outline Case study Prevalence of diabetes & IGT in the child bearing period Preconception care of women with diabetes Management of gestational diabetes Postpartum monitoring Conclusion

4. Case Study 31 year old woman G1P0 presents to the clinic at 6 weeks’ gestation Known type 2 diabetes on Glibenclamide and Metformin HbA1C is 8.1% She expresses concerns about the impact on her health and her future newborn How should she be managed?

5. Outline Case study Prevalence of diabetes & IGT in the child bearing period Preconception care of women with diabetes Management of gestational diabetes Postpartum monitoring Conclusion

6. Prevalence of Diabetes & IGT in the child bearing period Diabetes 20-29 years: 2.2 % 30-39 years: 8.9 % 40-49 years: 15.4 % IGT 20-29 years: 5.9% 30-39 years: 11.8% 40-49 years: 15.9%

7. Prevalence of Diabetes and IGT in the childbearing period 20-29 years: 8.1% 30-39 years: 20.7% 40-49 years: 31.3%

8. Outline Case study Prevalence of diabetes & IGT in the child bearing period Preconception care of women with diabetes Management of gestational diabetes Postpartum monitoring Conclusion

9. Preconception Care Elevated maternal glucose or HbA1C levels during embryogenesis is associated with high rates of spontaneous abortions and major malformations in newborns Unfortunately, unplanned pregnancies occur in about two-thirds of women with diabetes Preconception Care of Women With Diabetes Diabetes Care 27: 76S-78S.

10. Preconception Care Counselling about the risk of malformations Use of effective contraception

11. Preconception Care Program Multidisciplinary team Internist Obstetrician Diabetes educators The patient is the most active member

12. Preconception Care Program Patient education about the effects of diabetes on pregnancy outcomes Appropriate use of contraception Diabetes self-management skills Follow up

13. Preconception Care : goals of treatment Optimal HBA1C : Medical nutrition therapy (MNT) Self-monitoring of blood glucose (SMBG) Self-administration of insulin and self- adjustment of insulin doses Education about hypoglycaemia Physical activity

14. Preconception Care : Initial visit Medical & obstetric history Duration and type of diabetes (1 or 2) H/O acute complications H/O chronic complications Diabetes management : Insulin regimen, oral hypoglycaemic, SMBG, diet, physical activity

15. Preconception Care: Physical Examination Blood pressure, including orthostatic Fundoscopy Cardiovascular examination Neurological examination

16. Preconception Care : Laboratory evaluation HbA1C measurement Serum creatinine Albumin/creatinine ratio or 24 hour albumin excretion rate. Protein excretion >190 mg/24 hours: at a 3- fold increased risk for hypertensive disorders during pregnancy

17. Preconception Care : Laboratory evaluation Those with protein excretion >400 mg/24 hours are at risk for intrauterine growth retardation during later pregnancy ACE inhibitors should be stopped TSH and/or FT4 in women with type 1 diabetes

18. Preconception Care : Management plan Counselling about The risk and prevention of congenital anomalies fetal and neonatal complications of maternal diabetes effects of pregnancy on maternal diabetic complications

19. Preconception Care : Management plan Counselling about risks of obstetrical complications that occur with increased frequency in diabetic pregnancies the need for effective contraception until glycemia is well controlled

20. Preconception Care : Selection of antihyperglycemic therapy Insulin is the gold standard: efficacy, does not cross placenta Oral hypoglycemic currently not recommended

21. Preconception Care: Goals for SMBG Pre-meals capillary plasma glucose 4.4 – 6.1 mmol/L 2 hours postprandial capillary plasma glucose < 8.6 mmol/L Follow-up: 1 to 2 months’ intervals

22. Preconception Care: Special considerations Hypoglycemia Retinopathy: glycemic control, laser photocoagulation

23. Preconception Care: Special considerations Hypertension frequent concomitant or complicating disorder pregnancy induced hypertension occurs more frequently Aggressive control ACE inhibitors, B-blockers and diuretics avoided

24. Preconception Care: Special considerations Nephropathy renal function: serum creatinine and urinary protein excretion - potential impact of pregnancy on proteinuria - impact of renal insufficiency on fetal growth and development.

25. Preconception Care: Special considerations Nephropathy Incipient renal failure (Creatinine clearance 40% Less severe nephropathy → transient worsening of renal function

26. Preconception Care: Special considerations Neuropathy autonomic neuropathy: gastroparesis, urinary retention, hypoglycemic unawareness, or orthostatic hypotension Peripheral neuropathy, especially carpal tunnel syndrome, may be exacerbated by pregnancy.

27. Preconception Care: Special considerations Cardiovascular disease Untreated CAD is associated with a high mortality rate during pregnancy Exercise tolerance should be normal

28. Preconception Care: Special considerations At the earliest possible time after conception, pregnancy should be confirmed by laboratory assessment (urinary or serum B-hCG). The woman should be reevaluated by the health care team

29. Outline Case study Prevalence of diabetes & IGT in the child bearing period Preconception care of women with diabetes Management of gestational diabetes Postpartum monitoring Conclusion

30. Management of Gestational Diabetes (GDM) Definition & Prevalence glucose intolerance that is first detected during pregnancy prevalence is 7% worldwide. Gestational diabetes mellitus. Diabetes Care 2004; 27 Suppl 1:S88.

31. GDM: Detection & Diagnosis Risk assessment at the first prenatal visit High risk patients: obesity personal history of GDM strong family history of diabetes ethnic group with a high prevalence of diabetes

32. GDM: Detection & Diagnosis Women at high risk of GDM should have glucose testing at the first antenatal visit If not found to have GDM at that initial screening, retested at between 24 and 28 weeks gestation

33. GDM: Detection & Diagnosis Two-step approach An initial screening: plasma glucose 1 hour after a 50-g oral glucose load (glucose challenge test – GCT). A value above 7.8 mmol/L identifies 80% of women with GDM. Confirmed with an OGTT using 75 or 100 g glucose load.

34. GDM: Detection & Diagnosis Diagnosis of GDM with a 100-g oral glucose load Fasting5.3 mmolL 1-h10.0 2-h8.6 3-h7.8 Diagnosis of GDM with a 75-g oral glucose load Fasting5.3 mmolL 1-h10.0 2-h8.6

35. GDM: Detection & Diagnosis One-step approach Cost-effective in high-risk populations

36. GDM: Obstetrics and Perinatal considerations Increase in the risk of intrauterine fetal death during the last 4–8 weeks of gestation Fetal macrosomia and its associated risk of shoulder dystocia and birth trauma Neonatal hypoglycemia, jaundice, polycythemia, and hypocalcemia Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477-2486.

37. GDM: Obstetrics and Perinatal considerations Increased frequency of Maternal hypertensive disorders Need for cesarean delivery - Fetal growth disorders - Alterations in obstetric management due to the knowledge that the mother has GDM

38. GDM: Long term considerations Women with GDM are at increased risk of developing diabetes, usually type 2, after pregnancy Offspring of women with GDM are at increased risk of obesity, glucose intolerance, and diabetes in late adolescence and young adulthood

39. GDM: Therapeutic strategies Medical Nutrition Therapy (MNT) Goals: achieve normoglycemia prevent ketosis provide adequate weight gain contribute to fetal wellbeing

40. GDM: Therapeutic strategies Medical Nutrition Therapy (MNT) Calorie allotment BMI of 22 to 27: 30 kcal/kg per day BMI 27 to 29: 24 kcal/kg per day BMI > 30: 12 to 15 kcal/kg per day BMI less than 22: 40 kcal/kg per day

41. GDM: Therapeutic strategies Medical Nutrition Therapy (MNT) Carbohydrate intake: 35 to 40% Protein: 20% Fat: 40%

42. GDM: Therapeutic strategies Medical Nutrition Therapy (MNT) Calorie distribution: 3 meals and 3 snacks Overweight: snacks are eliminated. Breakfast: 10% of total calories Lunch: 30% Dinner: 30% Snacks: 30%

43. GDM: Therapeutic strategies Glucose monitoring: SMBG: Fasting and 2 hours postprandial Goals:FPG < 5.3 mmol/L 2 hours postprandial < 6.5 mmol/L HbA1C every 4 weeks American College of Obstetricians and Gynecologists. Gestational Diabetes. ACOG practice bulletin #30, American College of Obstetricians and Gynecologists, Washington, DC 2001.

44. GDM: Therapeutic strategies Insulin 15% requires insulin When diet fails to maintain SMBG at the following levels: - Fasting plasma glucose 5.3 mmol/L - 2 hours postprandial plasma glucose 6.5 mmol/L

45. GDM: Therapeutic strategies Insulin Premixed insulin is not appropriate If FPG is high, an intermediate acting insulin is given at bedtime. if the postprandial blood glucose high, short acting insulin is given before the meals

46. GDM: Therapeutic strategies Insulin if both fasting and postprandial blood glucose high, an intermediate acting insulin is given before breakfast and at bedtime and a short acting insulin is given tid before meals

47. GDM: Therapeutic strategies Insulin dose varies in different populations because of varied rates of obesity and ethnic characteristics. Intermediate acting: 40% of total daily dose Regular Insulin: 60% of total daily dose

48. GDM: Therapeutic strategies Insulin dose No absolute rule Dose distribution is modified according to - individual requirements - amount she will eat at each meals. Morning sickness should be taken in consideration.

49. GDM: Therapeutic strategies Insulin dose greater in obese women may need to be increased progressively as pregnancy advances to term SMBG guides the doses and timing of the insulin regimen

50. GDM: Therapeutic strategies Insulin dose The evening dose of intermediate acting insulin is modified according to the fasting capillary blood glucose The pre-meals short acting insulin dose is modified according to the postprandial capillary blood glucose.

51. GDM: Therapeutic strategies Short acting insulin analogues Insulin lispro and aspart, currently used in pregnancy Acceptable safety profiles Minimal transfer across the placenta No evidence of teratogenesis

52. GDM: Therapeutic strategies Short acting insulin analogues improve postprandial glucose excursions lower risk of delayed postprandial hyperglycemia. Long acting insulin analogues (Insulin Gargline and Detemir) not recommended for use in pregnancy at present.

53. GDM: Therapeutic strategies Oral hypoglycemic agents Concerns: Transplacental passage → fetal teratogenesis, prolonged neonatal hypoglycemia Most restrospective studies have not demonstrated an ↑ risk of maformed infants

54. GDM: Therapeutic strategies Metformin decreases hepatic glucose output improving peripheral glucose uptake, thus reducing insulin resistance may be a more logical alternative to insulin for women with GDM who are unable to cope with the increasing insulin resistance of pregnancy

55. The Metformin in Gestational Diabetes (MiG) trial Prospective randomized multicenter trial Testing the hypothesis that metformin compared with insulin, is associated with: - similar perinatal outcomes, - improved markers of insulin sensitivity in the mother and baby - improved treatment acceptability A Trial in Progress: Gestational Diabetes: Treatment with metformin compared with insulin (the Metformin in Gestational Diabetes [MiG] trial) Janet A Rowan. Diabetes Care. Alexandria: Jul 2007. Vol. 30 pg. S214, 6 pgs

56. The Metformin in Gestational Diabetes (MiG) trial Women with GDM at 20-33 weeks The MiG trial will address the efficacy and detailed safety of metformin Long-term follow-up of offspring will examine whether treatment influences later health

57. Comparison of glyburide & Insulin in women with GDM 404 women with GDM randomly assigned between 11 & 33 weeks to receive glyburide or insulin primary end point: achievement of the desired level of glycemic control Secondary end points: maternal and neonatal complications Langer O, Conway DL, Berkus MD, Xenakis EM-J, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134-1138.

58. Comparison of glyburide & Insulin in women with GDM no significant differences in % of infants who had Macrosomia Lung complications Hypoglycemia Admitted to a neonatal intensive care unit Fetal anomalies

59. Comparison of glyburide & Insulin in women with GDM Same degree of glycemic control Cord-serum insulin concentrations were similar in the two groups Glyburide was not detected in the cord serum of any infant in the glyburide group.

60. Comparison of glyburide & Insulin in women with GDM Conclusion In women with GDM, glyburide is a clinically effective alternative to insulin As the study was conducted after the period of organogenesis the effects on the incidence of congenital anomalies could not be assessed.

61. GDM: Therapeutic strategies Physical exercise Decreases insulin resistance. Women without medical or obstetrical contraindications should be encouraged to start or continue a program of moderate exercise to lower glucose concentrations

62. GDM: Therapeutic strategies Timing and mode of delivery GDM is not of itself an indication for cesarean delivery or for delivery before 38 completed weeks of gestation. Prolongation of gestation past 38 weeks increases the risk of fetal macrosomia without reducing cesarean rates, so that delivery during the 38th week is recommended unless obstetric considerations dictate otherwise.

63. GDM: Therapeutic strategies Intrapartum blood glucose control Maternal hyperglycemia should be avoided during labor maternal glucose concentrations should be maintained between 4.0 – 7.0 mmol/L. Insulin infusion is rarely needed during labor (except in type 1 diabetes)

64. GDM: Therapeutic strategies Intrapartum blood glucose control At delivery of the placenta, insulin infusion is stopped When the patient resumes oral feeds, S/C insulin is resumed if required

65. Outline Case study Prevalence of diabetes & IGT in the child bearing period Preconception care of women with diabetes Management of gestational diabetes Postpartum monitoring Conclusion

66. GDM Postpartum monitoring OGTT 6 weeks postpartum using criteria used for the general population If normal, reassessment of glycemia yearly IFG or IGT: diabetic diet and exercise program. Offspring followed closely for the development of obesity and/or abnormalities of glucose tolerance.

67. Case Study 31 year old woman G1P0 presents to the clinic at 6 weeks’ gestation Known type 2 diabetes on Glibenclamide and Metformin HbA1C is 8.1% She expresses concerns about the impact on her health and her future newborn How should she be managed?

68. Outline Case study Prevalence of diabetes & IGT in the child bearing period Preconception care of women with diabetes Management of gestational diabetes Postpartum monitoring Conclusion

69. A multidisciplinary team work is essential for preconception care and management of GDM Maternal glycemic control is crucial to improving pregnancy outcomes Management is simple and just requires awareness and organisation