DIABETES IN PREGNANCY

1. DIABETES IN PREGNANCY Josephine Carlos-Raboca, MD

2. Pregnancy is a time when serial metabolic changes in the mother are carefully regulated to provide optimum substrate to mother and fetus.

3. GOALS: • Normal outcome of index pregnancy. • Decrease risk for abnormal glucose and insulin homeostasis. • Mother (before, during, after pregnancy). • Infant subsequent generations.

4. Gestational Diabetes Mellitus (GDM) • Any degree of glucose in tolerance with onset or first recognition during pregnancy. • 4th International Workshop-Conference on GDM, 1998.

5. Pregestational Diabetes Mellitus • Diabetes diagnosed before pregnancy.

6. Prevalenceof GDM • 1 – 14% • USA--- 3-5% • MMC (Asian Population) – Raboca et al 13.4%

7. Perinatal Complications: • Macrosomia • Respiratory Distress Syndrome (RDS) • Hypocalcemia • Hyperbilirubinemia • Hypoglycemia • Polycythemia

8. Congenital Malformations • Skeletal • Cardiac (septal and outflow tract lesions) • CNS and neural tube defects • Gastrointestinal Defects • Genitourinary Tract lesions

9. Maternal and Fetal Factors of Teratogenesis • Genetic Background • Teratological Period • Disturbances in Maternal-Fetal Transport • Concentrations of Metabolites • Hyperglycemia • Hyperketonemia • Somatomedin inhibitors • Arachidonic/myoinositol deficiency • Generation of free oxygen radicals • Genotoxity Teratology 1997

10. Objectives: • Recognize GDM • Know how to provide nutritional plan • Know how to give insulin • Discuss preconception and postpartum care • Recognize special problems of pregestational diabetes

11. Case I • 31 year old female G1 PO, Age of Gestation 20 weeks Weight gain of 5 kg in the last 4 weeks BMI (pre-pregnant) = 30 • Height: 165 cm • actual body weight 90 kg • Family History (+) DM in mother

12. Would you recommend testing for GDM at this time or later at 24th to 28th weeks of gestation

13. Risk Factors of GDM • Age > 25 years of age • Obesity – BMI > 27 kg/m2 or > 20% over DBW • Family History of diabetes in first degree relative • Ethnicity (Hispanic American, Native American, Asian American, Pacific Islander)

14. ADA 2001 • Low risk – no test • Average risk – test at 24th-28th week • High risk – test at 1st visit if negative repeat at 24 – 28 weeks. ASGODIP • Test at 1st visit and every trimester if negative in previous test

15. 50 gm glucose challenge test was 150 mg/dl • 100 gm OGTT F=102; 1H=192; 2H=155; 3H=140 • Does this patient have GDM?

16. Diagnosis of GDM 100 gm OGTT 75 gm OGTT mg/dl mml/L mg/dl mml/L F 95 5.3 95 5.3 1H 180 10.0 180 10.0 2H 155 8.6 155 8.6 3H 140 7.8 > 2 values met = GDM ASGODIP, WHO European Diabetes Policy Group 1992-1998 75 gm OGTT, 2H>140

17. Prescribe diet for this patient • For normal weight – 30 kcal/kg of Present BW • For overweight – 24 kcal/kg of Present BW • For morbidly obese – 12 kcal/kg Present BW • 3 meals, 3 snacks, 40% of total calories = CHO Medical Management of Pregnancy Complicated by Diabetes

18. With diet, preprandial capillary blood glucose level were 70 - 80 mg/dl,2HPPCBG 95 – 115 mg/dl • Would she require insulin?

19. ADA 2001 Insulin Required if diet fails to maintain glucose at following levels. • Fasting whole blood glucose < 95 mg/dl (5.3 mml/L) • Fasting Plasma Glucose < 105 mg/dl (5.8 mml/L) OR • 1H Postprendial whole blood glucose < 140 mg/dl (7.8 mml/L) • 1H Postprendial Plasma Glucose < 155 mg/dl (8.6 mml/L) OR • 2H Postprandial whole blood glucose < 120 mg/dl (6.7 mml/L) • 2H Postprandial Plasma Glucose < 130mg/dl (7.2 mml/L)

20. How would you follow up this patient Postpartum? • What are her chances of developing diabetes?

21. 75 gm OGTT > 6 wks. postpartum FPG every year x 3 years

22. 50% in 20 years timePredictors of DM • maternal obesity • fasting hyperglycemia • duration of time from index pregnancy

23. TRIPOD

24. Case 2 • 28 years old Go Po • diabetic X 1 year • desires pregnancy

25. When is the best time for patient to get pregnant? • What advise would you give her?

26. Counseling about risk of malformation with poor control • Use of low dose estrogen progestogen contraceptive till good metabolic control is achieved. Goals: • HBA is 1% above normal • Preprandial CBG 70-110 mg/dl (3.9-5.6mml/L) CPG 80-110 mg/dl (4.4-6.1 mml/L) • 2H Postprandial CBG < 140 mg/dl (7.8mml/L) CPG < 155 mg/dl (8.6mml/L)

27. 4-7 X / day preprandial 1 hour or 2 hour post prandial

28. What other medical problems should you consider in a diabetic pregnant?

29. Acceleration of retinopathy • Pregnancy induced hypertension • Progression of Nephropathy

30. What is your goal for glycemic control during labor?

31. 120 mg/dl • D5 0.45 NSS at 100-125 ml/hour • CBG every 1-4 hours • Insulin infusion to start at 1unit/hour of regular insulin if CBG > 120 mg/dl

32. THANK YOU.

33. HYPERGLYCEMIA AND ADVERSE PREGNANCY OUTCOME STUDY (HAPO) Background: Overt diabetes clearly increases the risk of adverse pregnancy outcome What level of glucose intolerance short of diabetes increases the risk of adverse pregnancy outcome?

34. Study protocol • 75gm OGTT 24-32 weeks (average 28) 0,1,2 hours • Venous plasma, enzymatic method • Results provided if FPG> 105 (5.8) 2 hour > 200 (11.1) any value <45(2.5) otherwise blinded to caregivers

35. Endpoints • Relationship between maternal hyperglycemia and cesarian rate macrosomia rate fetal hyperinsulinemia neonatal obesity (skinfold thickness) neonatal hypoglycemia rate other morbidities

36. Study Protocol • Routine prenatal care • Daily kick count from 28 weeks • Random venous plasma glucose at 34-37 weeks if > 160 mg/dl (8.9) or <45 • Umbilical cord glucose and C-peptide levels • Routine neonatal care • Neonatal blood glucose at 1-2 hours of age • First feeding 2 hours after birth (may nurse earlier if desired)

37. Interim Study Report • Enrollment: 9396 women • Deliveries:5282 primary CS 14.5% repeat CS 7.3% prenatal loss 5.5/1000 • Number of OGTT: 7160 • Unblinded: 158 (2.2%)

38. Interim… • Glucose levels FPG 10% > 90 1 hour 15% > 160 2 hour 4% > 140

39. Summary • Preliminary data from HAPO enrollees confirm the safety of the study protocol and yielded the predicted prevalence of “lesser degrees”of glucose intolerance that should permit an adequate test of the study hypothesis.

40. Study Hypothesis • Hyperglycemia in pregnancy less severe than overt diabetes is associated with increased risk of adverse maternal fetal and neonatal outcomes that is independently related to the degree of metabolic disturbance.