بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Diabetes Mellitus And Pregnancy BY Mohammed shereif MD of Internal Medicine Endocrine unit Faculty of Medicine-Mansoura University

3. AGENDA: • Review On Diabetes Mellitus. • Endocrinology Of Pregnancy. • Diabetes Mellitus And Pregnancy. • Complicationsof Diabetes on pregnancy. • Management.

4. Review On Diabetes Mellitus

5. DIABETES MELLITUS:DEFINED Diabetes is a group of metabolic diseases characterized by hyperglycemia. • Hyperglycemia resulting from defects in insulin secretion, insulin action, or both. • The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels

6. DIABETES CLASSIFICATION: • Type 1 (IDDM). • Type 2 (NIDDM). • Gestational diabetes. • Other specific types.

7. Criteria for the diagnosis of diabetes mellitus:

8. Endocrinology Of Pregnancy

9. The placenta produces larger quantities of more hormones than any other human organ. • Placental Diabetogenic Hormones are: • Progesterone, Cortisol, GH • Human Placental Lactogen (HPL), Prolactin • Placental hormones affect glucose and lipid metabolism to ensure that fetus has ample supply of nutrients.

10. Changes in maternal metabolism during normal pregnancy: • Decreased fasting plasma glucose level. • Increased post prandial plasma glucose. • Increased plasma insulin level and IR. • ß- cell hypertrophy and hyperplasia. • Increased fat metabolism. • Increased ketone production. • Decreased circulating amino acids. • Decreased glucose production in the liver. •  renal threshold for glucose  glycosuria.

11. Pregnancy Pathophysiology: • Insulin resistance occurs because the hormonal changes associated with pregnancy partially block the effects of insulin. • Maternal pancreatic beta cells increase insulin secretion almost three fold to compensate for increased insulin resistance. • If the mother’s pancreas is unable to produce sufficient insulin to overcome insulin resistance, maternal glucose levels increase and GDM occurs. • GDM may disappears after pregnancy because the hormonal changes that caused insulin resistance are no longer present.

12. Diabetes Mellitus And Pregnancy

13. Diabetes in Pregnancy:Types • Gestational Diabetes Mellitus (GDM) • Type A1:abnormal (OGTT) but normal blood glucose levels during fasting and 1-2 hours after meals. • Type A2:abnormal (OGTT) with abnormal glucose levels during fasting and/or after meals. • Pregestational Diabetes Mellitus • Type 1: autoimmune process that destroys pancreatic B cells. • Type 2 (“lifestyle diabetes”):acquired insulin resistance related to obesity.

14. Diabetes in Pregnancy:Classification

15. Pregestational Diabetes:Types 1 and 2

16. Gestational Diabetes Mellitus: “Any degree of glucose intolerance with onset or first recognition during pregnancy.” • The definition applied whether insulin or only diet modification is used for treatment of GDM. • It does not exclude the possibility that unrecognized glucose intolerance may have antedated or begun concomitantly with the pregnancy.

17. Risk Assessment

18. Risk factors for developing GDM: • A family history. • Gestation diabetes in a previous pregnancy. • Obesity and BMI > 30 kg/m2 • Older maternal age > 30 y. • Previous still birth or spontaneous miscarriage. • A previous delivery of a large baby ( > 9 bounds). • Women of hispanic, or African American.

19. Low risk for GDM: • Age less than 25 years. • Normal weight before pregnancy (BMI less than 25 kg/m2). • Member of an ethnic group with a low prevalence of GDM • No first degree relative with diabetes mellitus. • No history of abnormal glucose tolerance. • No history of poor obstetric outcome.

20. Screening For GDM

21. Screening Strategy Universal Selective based on Performing GCT in all pregnant women Obesity Age  25 years Familial diabetes Poor obstetric outcome Abnormal glucose metabolism High GDM prevalence ethnic groups Clinics in laboratory medicine, 21.1 March 2001, 173-192 Diabetes Care 23.1, ADA clinical practice recommendation 2000

22. Whom to Screen for GDM ? • Low Risk Group • No screening required for GDM • Intermediate Risk Group • Screen around 24–28 weeks of gestation • High Risk Group • As soon as possible after conception • Must - before 24–28 weeks of gestation • Better do a full 3 hr OGTT for GDM • If negative  screening in 2nd & 3rd trimester

23. Screening strategies for GDM • The approach One-step approach Two-step approach

24. One step approach: • Perform a diagnostic oral glucose tolerance test (OGTT) without prior plasma or serum glucose testing. • Cost effective in high risk patients or population.

25. Initial screening plasma or serum glucose 1h after 50gm oral glucose load. Exceeding the Glucose threshold value or the GCT • Two step approach: Diagnostic OGTT

26. Two step approach  glucose threshold > 140 mg  80% of women with GDM and the yield is further increased to 90% by using a cutoff of > 130 mg/dl. • POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS OF GESTATIONAL DIABETES!!!

27. 50-g oral glucose challenge • The screening test for GDM, may be performed in the fasting or fed state. Sensitivity is improved if the test is performed in the fasting state. • A plasma value above 130 - 140 mg/dl one hour after is commonly used as a threshold for performing a 3-hour OGTT. • If initial screening is negative, repeat testing is performed at 24 to 28 weeks.

28. Diagnosis Of GDM

29. 3 hour Oral glucose tolerance test • Prerequisites: • Normal diet for 3 days before the test. • At least 10 hours fast. • Test is done in the morning at rest. Giving 75 gm (100 gm by other authors) glucose in 250 ml water orally. • 2 or more values greater than or equal to the following cutoffs is diagnostic of GDM. • single abnormal value indicates CHO intolerance.

30. Diagnostic Criteria for GDM • For ADA criteria 2 or more values from either 100 or 75 g OGTT must be met or exceeded to make the diagnosis of GDM • For WHO criteria, one of the 2 values must be met or exceeded to make the diagnosis of GDM

31. Complications of Diabetes on pregnancy

32. NEONATAL COMPLICATIONS: • Congenital anomalies. • Premature delivery. • Perinatal asphyxia. • Macrosomia and Shoulder Dystocia. • Respiratory distress syndrome. • Hyperbilirubinemia.

33. Cardiomyopathy. • Polycythemia and hyperviscosity syndrome. • Metabolic complications. • Late effects on the offspring: • Increased risk of IGT. • Future risk of T2DM. • Risk of Obesity.

34. Macrosomic Newborn (4.2kg)

35. Erb’s palsy Shoulder Dystocia

36. Maternal COMPLICATIONS: • Difficult diabetic control (Ketoacidosis). • Repeated infections during pregnancy and puerperium. • PET and eclampsia: 15-20%. • Operative and difficult deliveries: increased CS rate. • Postpartum hemorrhage. • Increase incidence of diabetic complications: nephropathy, neuropathy and retinopathy.

37. Management

38. Prepregnancy Evaluation Of Diabetic Women • Complete history and physical examination. • Multidisciplinary team including obstetricians, endocrinologists, dieticians, & midwives  optimize outcome. • To achieve normoglycemia as far as possible: • FBS < 95 mg/dL. • 1h PP < 140 mg/dL. • 2h PP < 120 mg/dL.

39. Monitoring: • SMBG  intermittent office monitoring. • For women treated by insulin  1h post -prandial monitoring is superior to pre-prandial monitoring. • Urine glucose  not useful in GDM. • Urine ketone  be useful in detecting insufficient caloric or carbohydrate intake in women treated with calorie restriction.

40. Target Blood Glucose Values Our blood glucose goals in pregnant diabetic women are: • ACOG: • Fasting glucose concentrations ≤ 95 mg/dL (5.3 mmol/L). • Preprandial glucose concentrations no higher than 100 mg/dL (5.6 mmol/L). • One-hour postprandial glucose concentrations no higher than 140 mg/dL (7.8 mmol/L).

41. Two-hour postprandial glucose concentrations no higher than 120 mg/dL (6.7 mmol/L). • Mean capillary glucose 100 mg/dL (5.6 mmol/L) and glycosylated A1C ≤ 6 percent (ACOG, 2005). • ADA: • Preprandial glucose concentrations 80 to 110 mg/dL (4.4 to 6.1 mmol/L). • Two-hour postprandial glucose concentrations no higher than 155 mg/dL (8.6 mmol/L)(ADA, 2004).

42. Nutritional counseling • Registered dietitian. • Individualization of medical nutrition therapy (MNT). • Adequate calories and nutrients to meet the needs of pregnancy. • Non caloric sweeteners.

43. Nutritional Recommendations Distribution of total calories is: • 35-45 % carbohydrates. • 20-25 % protein. • 35-40 % fat. • Most programs suggest three meals and three snacks, however, in overweight and obese women the snacks are often eliminated.

44. Exercise ! • Moderate regular exercise such as: walking, cycling or swimming are excellent forms of exercise for pregnant women. Keeping well-hydrated and well-nourished is essential

45. Medical Therapy: • If normoglycemia cannot be maintained by medical nutritional therapy, then anti-hyperglycemic agents should be initiated. • Insulin. • Oral anti-hyperglycemic agents.

46. Insulin: • Insulin therapy is recommended when MNT fails to maintain self monitored glucose at the following level (ACOG&ADA): • FBG < 95 mg/dl or • 1h PPPG < 130-140mg/dl or • 2h PPPG < 120 mg/dl. • Use of insulin preparations of low antigenicity will minimize the transplacental transport of insulin antibodies: human insulin is the least immunogenic of the commercially available preparations.

47. Regular insulin, which is often used in pregnancy for the treatment of diabetes has some drawbacks: • It starts its action from 30 to 60 min after subcutaneous injection and it peaks too late (2-4 h after injection) to be very effective in postprandial control. • In addition, it lasts too long (duration of 6-8 h), with an increased risk of postprandial hypoglycemia.

48. Insulin molecules clump in hexamers that must be broken up to dimers and monomers before absorption, so delaying their effectiveness. • Therefore, in the last few years insulin analogues started to be used to optimize glucose control during pregnancy.

49. The New Insulin Analogues Insulin Glargine Insulin Detemir Insulin Lispro Insulin Aspart Insulin Glulisine Rapidly Acting Long acting

50. Insulin Lispro: • There are various safety issues to consider: Immunogenicity,Teratogenicity, Embryotoxicity, and Retinopathy. • The studies reported to date suggest that insulin lispro may be considered a treatment option in patients with GDM. • Insulin Aspart: • Aspart insulin is now approved for use in pregnancy and offers a valuable treatment option.