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CURRENT CONCEPTS DIABETES IN PREGNANCY DIANA CLOKEY MSRD,RPH,CDE SCHOOL OF MEDICINE/DEPT OB/GYN UNIVERSITY OF NEW MEXIC

CURRENT CONCEPTS DIABETES IN PREGNANCY DIANA CLOKEY MSRD,RPH,CDE SCHOOL OF MEDICINE/DEPT OB/GYN UNIVERSITY OF NEW MEXICO. OBJECTIVES . Understanding pathophysiology of fetal and neonatal complications in pregnancy Discuss the diagnosis and management of gestational diabetes mellitus

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CURRENT CONCEPTS DIABETES IN PREGNANCY DIANA CLOKEY MSRD,RPH,CDE SCHOOL OF MEDICINE/DEPT OB/GYN UNIVERSITY OF NEW MEXIC

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  1. CURRENT CONCEPTS DIABETES IN PREGNANCY DIANA CLOKEY MSRD,RPH,CDE SCHOOL OF MEDICINE/DEPT OB/GYN UNIVERSITY OF NEW MEXICO

  2. OBJECTIVES • Understanding pathophysiology of fetal and neonatal complications in pregnancy • Discuss the diagnosis and management of gestational diabetes mellitus • Understanding the pharmacology of the different insulin/oral hypoglycemic agents • Introduce on going research in the field of Diabetes in Pregnancy

  3. INCIDENCE OF DIABETES IN PREGNANCY - Incidence in all pregnancies 7% • 80-90% of patients with diabetes complicating pregnancy have gestational diabetes. 200,000 cases annually • 10-20% of patients with diabetes complicating pregnancy have pre-existing (Type 1 and Type 2)

  4. BOTH GDM AND TYPE 2 ARE HETEROGENEOUS DISORDERS Pathophysiology is characterized by - peripheral insulin resistance - Impaired regulation of hepatic glucose production - Chronic hyperinsulinemia or impaired beta cell secretion - Auto antibodies presents 10-30% of GDM - Single gene mutation (MODY 2) ~ 10% cases of GDM

  5. Epidemiology • Incidence of GDM has increased across all ethnic groups • Increase of GDM in younger women • Parallels obesity epidemic • Maternal obesity strongly linked to excessive birth weight

  6. DEFINITION OF GDM Any degree of glucose intolerance with onset or first recognition during pregnancy Diabetes Care January 2004

  7. DIABETES FETOPATHY

  8. Conception of 8th week Malformations: A1C>10 Caudal regression (3wk) NTD (4 wks) Cardiac (5 wks) Renal (5 wks) GI (6 wks ) 8th week to delivery Chronic hypoxia Intrauterine death Hyperinsulinism Macrosomia Organomegaly Polyhydraminos RDS ADVERSE EFFECTS IN OFFSPRING

  9. LONG – TERM EFFECTS IN CHILDREN - Obesity - Abnormal glucose tolerance - neurospychological defects

  10. DIABETES EFFECT ON THE PREGNANCY • Dystocia • Preeclampsia • Pyelonephritis • Pelvic trauma • C-section

  11. SCREENING STRATEGY • Risk assessment for GDM at first prenatal visit Low Risk Average Risk High Risk

  12. LOW RISK STATUS (requires no glucose testing) • Age < 25 • Weight normal before pregnancy • Member of an ethnic group with low prevalence of GDM • No known diabetes in first-degree relatives • No history of abnormal glucose tolerance • No history of poor obstetric outcome • Normal birthweight of mother (2500-4400 grams) Petitt Diabetes Care 21 : B 138 1998

  13. Average Risk • Two–step approach • 24 – 28 wks • 1 hr 50 gram – no fasting necessary • Venous plasma (≤140 mg/d1) identifies 80% of women with GDM. A value > 130mg/d1 identifies 90% of women with GDM • 3hr GTT if patient fails screen

  14. HIGH RISK • Prior GDM, obesity, advanced maternal age, non-white ethnicity • Perform blood glucose test as soon as feasible • One step approach (75gm 2h GTT) • Repeat at 24–28 wk if needed

  15. DIAGNOSTIC CRITERIA FOR GDM

  16. Fasting Preprandial 1 hr after meals 2 hr after meals 30-90 mg/d1 60-105 mg/d1 <140 mg/d1 <120 mg/d1; CONTROL OF MATERNAL GLYCEMIA (TARGET GLUCOSE LEVELS) • Avoid hypoglycemic <60mg/dl • PP measurements timed from start of • meals

  17. MEDICAL NUTRITION THERAPY (MNT) • MNT is the cornerstone of treatment – It is the only therapy for 40-85% of women with GDM • Goal: To provide calories and nutrients to sustain pregnancy with appropriate weight gain normoglycemcia and the absence of ketones Metzger Be etal Diabetes Care August 1998

  18. DIETARY RECOMMENDATIONS - Composition of diet 40% CHO, 20% PRO, 40%/fat - Post prandial glucose should guide CHO intake - CHO should be distributed throughout the day in small frequent meals • NO changes in calorie intake • Recommend use of maternal weight gain grids • Reaffirmed safety of non-nutritive sweetners

  19. RECOMMENDED WEIGHT GAIN DURING PREGNANCY IOM 1990

  20. GREAT VARIABILTY IN DAILY ENERGY INTAKE FOR PREGNANCY RANGE FROM 1500-2800KCAL/d • FOR GDM – underweight and normal weight woman should maintain energy intake to support adequate not excessive weight gain • Suggested range 30-35 kcal / kg IBW or PBW • Starting in 2nd + 3rd trimester ½ - 1 # per week

  21. - Avoid severe calorie restriction less than 1500kcal - 33 % calorie restriction 1600-1800-kcal provides improved glucose control and negative for ketones. Recommendation 24/kcal/kg - Avoid ketonuria or ketonemia children’s mental development-index-score and average Standford–Binet scores correlated inversely with 3rd trimester B-hydroxybutyrate MANAGEMENT OF OBESE GDM WOMEN Knopp RH et ak J.AM Col Nutr.1991

  22. NUTRITION PRACTICE GUIDELINES STATES: • Calorie requirements are monitored by following weight gain patterns urine ketone testing, assessing appetite and review food records. American Dietetic Ass. 1995

  23. NUTRITION GUIDELINES • Carbohydrate counting/Label reading • CHO restriction at breakfast • Avoid sugar, concentrated sweets, refined/ processed starches • Eliminate liquid CHO (juices), test milk • FDA has approved aspartame (Equal) sucralose (splenda), saccharine (sweet n low) for pregnancy • Encourage high fiber foods

  24. CARBOHYDRATE BUDGET Breakfast 1-2 carbohydrate Choices Lunch 3-4 carbohydrate Choices Supper 3-4 carbohydrate Choices Snack (1-3) 1-2carbohydrate Choices Amount of CHO typically found in a 1800-2400 calorie diet

  25. ROLE OF PHYSICAL ACTIVITY Women who are physically active before and in early pregnancy have a lower rate of GDM • 48-76% reduction in incidence of GDM • Acute effects is to lower BG 23mg/dl • Less or no use of medication Dempsey JC. Etal Diabetes Res Clinical practice 2004 Avory MD etal J. Met-Fer Med 2001

  26. SAFE EXERCISE • Monitor fetal activity and BG before and after exercise • Limit to light to moderate activity 15-30 minutes • Upper extremity exercise produces no uterine contractions • 3 episodes/wk> 15 minutes • No recommendations regarding type of exercise

  27. GLUCOSE MONITORING • Daily SMBG superior to intermittent monitoring • Fasting blood sugar most predictive of fetal demise • Post prandial sugars most predictive of macrosomia • GDM and Type 2 (test FBS and 2 hpp) Type 1 (FBS pre and post meals) • Allows patient flexibility in food choices

  28. KETONE URINE TESTING • Pre-breakfast urine testing to detect starvation ketosis • Illness • Blood glucose over 200 mg/dl

  29. CRITERIA TO BEGIN CONCURRENT THERAPY - When following diet, 20% above normal values are outside targets range - When nutritional parameters are compromised • Wt loss • Restriction of healthy foods • Nutritional adequacy • Ketones • Fetal abdominal circumference > 70% (u/s in early 3rd trimester)

  30. PHARMACOTHERAPY - insulin - oral hypoglycemic agents

  31. DRUG CATEGORY IN PREGNANCY A Well controlled human studies, no risk to fetus B Animal studies no risk to fetus, no well controlled studies in pregnant women CAnimal studies have shown adverse effects. No well controlled studies in pregnant women Potential benefits may warrant use despite potential risk

  32. OUT WITH THE OLD.... INSULINS NO LONGER PRODUCED - Regular pork insulin - NPH pork insulin - Ultralente - Lente

  33. TODAY’S INSULIN(BIOSYNTHETIC HUMAN INSULIN) - Fast acting analogs - Short acting regular - Intermediate acting NPH - Long acting glargine (Lantus)

  34. INSULIN USE • Human insulin is advocated to minimize the transplacental transport of anti-insulin antibodies • Rapid acting analogs preferable to Regular insulin • NPH insulin is the basal insulin of choice • No data demonstrating the superiority of any particular insulin regimen.

  35. LISPRO (HUMALOG) IN PREGNANCY • Antibody formation comparable to regular human insulin • Not detectable in cord blood • Similar or improved metabolic control • Less hypoglycemia • Enhanced patient satisfaction • ? Progression of diabetic retinopathy

  36. NEW INSULINS NOW AVAILABLE - Glulysine (Apidra) Fast acting analog - Detemir (Levemir) - Category C - long acting basal. Given twice/d - flat peakless concentration/time profile - Inhaled Insulin (Exubera) - used only for control of glucose after meals - dispense in 1mg(3u) or 3mg (8u). - may affect lung function. Contraindicated smokers; chronic lung disease - Cost 3-4 x more than injectables

  37. BEWARE OF VICIOUS CYCLE Increased Appetite Wt Gain Insulin resistance

  38. ORAL HYPOGLYCEMIA AGENTS • Glyburide vs. insulin (Langer NEJM 2000) • Similar levels of glycemic control • Acceptable alternative therapy to insulin if lifestyle fails • Obese and severely hyperglycemic women need closer follow-up

  39. ORAL HYPOGLYCEMIA AGENTS Glyburide (cat B) - Most effect with/slightly increased BW - Crosses placenta in very low levels - t½ 3-5h, peaks 2.75h - Best timing 1 hour before meal - Failure rate 20-30% -Failure rate when started < 30wks FBS > 110 and 1 hour BG > 140

  40. Biguanides (Metformin) (Cat B) - Utilized for insulin resistance & PCOS - Insulin sensitizer - Small molecule – crosses the placenta - Long – term studies are now in progress (MiG study) - No evidence teratogenesis - MiG TOFU (the offspring follow up) Can J Clinical Pharmacol. 2003; 10(4):179-183

  41. Glucosidase inhibitor (acarbose) - Category B - Promising - Not absorbed systemically - Recommendation is to start at low doses due to GI effects - Can only treat hypoglycemia with glucose

  42. Thiazolidineones (TZDs) - Category C - Crosses placenta levels of ½ the maternal blood level - No data in fetal safety - Depends on insulin release in mother - Has not been studied in pregnancy

  43. Exanatide (GLP-1 Agonist) • Category C • Byetta • Injection • Depends on insulin release in mother • Has not been studied in pregnancy

  44. Obstetrical Management • Fetal kick counts (32-32 weeks gestation) • NST’s/AFI’s begin at 32 weeks gestation for pre-existing and A2 GDM • Ultrasound for growth

  45. POPULATION PERSPECTIVE • GDM identifies younger women with glucose levels in the upper end of the population distribution during pregnancy. They may - never get diabetes - on their way to diabetes - already have diabetes

  46. POST PARTUM - 75g 2h OGTT at 6 weeks - Counseling and education - Recommend test one year after delivery then every 3 years (12% conversion rate 1 year; 50-60% conversion in 5-10 years)

  47. BREAST FEEDING AND GDM • Very limited data specific to GDM • Associated with lower rates of type 2 diabetes and reduced CHD risk in general population • Greatest protection > 6 months) • Glyburide/glipizide not found in breast milk

  48. HAPO STUDY Hyperglycemia and Adverse Pregnancy Outcome • Summary and Recommendations from 3rd International Workshop Conference on GDM: 1990 • “With respect to GDM, the heart of the matter is the relationship between the degree of glucose intolerance and or hyperglycemia and the risk of adverse maternal, fetal and neonatal outcomes. The highest priority should be given to efforts to develop international consensus on methods and definitions.”

  49. HAPO- STUDY DESIGN - Multicenter observational study of the association between maternal hyperglycemia and perinatal outcome • Investigator initiated • Tests no interventions- “not a clinical trial” • Will not answer treatment of diabetes

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