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1. Diabetes in pregnancy

2. Most common medical disorder complicating pregnancy GDM, 50% risk of having type 2 diabetes in 10 years Prevalence rising Increasing in Obesity Significant risks both to the mother and fetus Introduction…

3. Pregestational diabetes: 0.2 – 0.5 % , 65 % type II GDM: 1.4 – 14% A nation wide survey in USA,4 % 88 % GDM 12 % Pregestational Systematic review in low- and middle-income countries GDM: 0.40--24.3 % Pre-existing DM: 0--0.7 % Incidence

4. Classification Diabetes in pregnancy Pre-existing diabetes Gestational diabetes Pre-existing diabetes Type I Type II True GDM

5. CLASS DIABETES ONSET AGE (yr) DURATION (yr) VASCULAR DISEASE NEED FOR INSULIN OR ORAL AGENT Gestational Diabetes A1 A2 Any Any Any Any − − − + Pregestational Diabetes B >20 20 + + C 10 to 19 10 to 19 + + D <10 >20 + + F Any Any + + R Any Any + + T Any Any + + H Any Any + + MODIFIED WHITE CLASSIFICATION OF PREGNANT DIABETIC WOMEN

6. F= nephropathy H= heart disease R=proliferative retinopathy T= organ transplantation

7. Pregestational diabetes Overt diabetes criteria: Fasting plasma glucose ≥ 126 mg/dl HgBA1C ≥ 6.5% Random plasma glucose ≥ 200 mg/dl with classic symptoms 2-hr PG ≥ 200 mg/dl during 75-g OGTT

8. Effect of pregnancy on pre-existing DM Increase requirement for insulin doses Nephropathy A utonomic neuropathy Progress in diabetic retinopathy (2X) Hypoglycemia Diabetic ketoacidosis Preexisting DM in pregnancy

9. Effect of preexisting DM on pregnancy Maternal Increase risk of miscarriage Increase risk of preeclampsia Preterm birth Increase risk of infection Increase CS rate PPH Shoulder dystocia Polyhydramnios Preexisting DM…

10. Effect of preexisting DM on pregnancy (2) Fetal A . Congenital abnormalities Leading cause of perinatal mortality, 6–12 % B. Perinatal mortality C . Sudden unexplained intrauterine fetal death D. Macrosomia

11. (3) Neonatal Hypoglycemia Polycythemia Jaundice Electrolyte disturbances Cardiomyopathy RDS Preexisting DM…

12. Maternal hyperglycemia | Fetal hyperglycemia | Fetal pancreatic beta-cell hyperplasia | Fetal hyperinsulinaemia | Macrosomia, organomegaly , polycythemia, hypoglycemia, RDS

13. REPERCUSIONS ON : Embryo Fetus Newborn Abortions Malformations Growth alterations MACROSOMIA IUGR Dystocia Perinatal asphyxia Metabolic alterations Hypoglycemia Hypocalcemia Hyperbilirubinemia Polycythemia Alterations of maturity Respiratory distress syndrome

14. Pregnancy: exacerbation of diabetes-related complications Poorly controlled pregestational diabetes: serious endorgan damage Preexisting diabetes-related end-organ disease: adverse obstetric outcomes Maternal Morbidity

15. Diabetic retinopathy 1 ) Background retinopathy 2 ) P roliferative retinopathy Rapid institution of strict glycemic control: acute progression Proliferative retinopathy best treated with laser therapy Retinopathy

16. 5–10 % of pregnancies Mild-to-moderate nephropathy, no risk of deterioration Progression to end stage renal disease : Serum creatinine >1.5 mg/dl Severe proteinuria > 3 g per 24 hours Nephropathy Hypertensive disorders Uteroplacental insufficiency Iatrogenic preterm birth

17. 5–10 % of pregestational DM Preeclampsia, uteroplacental insufficiency, stillbirth Ideally, should be controlled before conception ACE inhibitor or angiotension II receptor blocker Discontinued before conception Calcium channel blockers H ypertension

18. Long-standing disease, nephropathy, hypertension Preexisting symptomatic coronary artery disease: contraindication to pregnancy Pregnancy-associated hemodynamic changes: myocardial infarction and death Coronary heart disease

19. Life-threatening emergency 5–10% pregnancies, type I DM Common risk factors: Infections Poor patient compliance Insulin pump failure Treatment with β-mimetic Antenatal corticosteroids New onset diabetes During pregnancy Higher incidence Develops more rapidly Less severe levels of hyperglycemia Diabetic Ketoacidosis

20. Fewer than one third of women Diabetologist , obstetrician and dietician Contraindications to pregnancy: I schemic heart dx Untreated proliferative retinopathy S evere renal impairment (creatinine>1.9mg/dl) Pre-conception Counselling

21. Achieve good glucose control before conception If A1c above normal range, intensive insulin therapy 3-4 injections/day of short and long acting insulin Self-blood glucose monitoring Retest every month until target A1c value achieved Preconceptional care…

22. 4 - 5 mg of folic acid daily, intermediate to high risk Indications: Previously affected child Family history of neural tube defect Insulin-requiring diabetes Treatment with valproic acid or carbamazepine Folic acid supplementation

23. Gestational diabetes: any degree of glucose intolerance with onset or first recognition during pregnancy P revalence: 6 % to 9% Increasing incidence in developing countries Gestational Diabetes Mellitus

24. Insulin resistance HPL  cortisol , estriol & progesterone  destruction of insulin by kidney & placenta  lypolysis  use of fat by fetus Leptin , tumor necrosis factor-α (TNF-α), and resistin Effect of pregnancy on Diabetes

25. Women with overt diabetes: Inability to respond to this stress Insulin requirement increase by 30 % W omen with borderline pancreatic reserve: Inadequate insulin production Diabetes revealed for the first time Insulin resistance…

26. Maternal complications Increase risk of hypertensive disorders Increase risk of caesarean and instrumental deliveries Increased Risk (40-60%) of developing type 2 DM within10-15yr

27. Fetal complications Macrosomia (>4 kg), postprandial hyperglycemia Birth trauma Perinatal mortality, fasting hyperglycemia Neonatal hypoglycemia, hyperbilirubinemia , polycythemia Children at risk for type 2 DM and obesity in life

28. Screening N o consensus regarding the optimal approach The major issues: U niversal or selective screening Which plasma glucose level to use ADA: selective screening better than universal ACOG : universal screening B ased on risk stratification .

29. High risk : one or more of the following: Marked obesity P ersonal history of GDM G lucose intolerance or glycosuria Previous congenital abnormal fetus Maternal age > 35 yrs Previous macrosomic infant Previous unexplained fetal death Strong family history of DM Low risk : all of the following: 1 . <25 years of age 2. Normal weight 3. Have no family history of DM 4. No history of glucose intolerance 5. Not a member of ethnic/racial group with high prevalence of DM 6. No history of poor obstetrical outcome Screening …

30. High risk: glucose testing as soon as possible If result negative, recheck at 24-28 weeks Intermediate risk: neither low or high-risk group S creen at 24-28 weeks Low risk category: screening not recommend Screening…

31. 1) One-step approach Diagnostic oral glucose tolerance test 2) Two-step approach Screening with glucose challenge test Screening…

32. O ne hour value > 140 mg/dl, sensitivity 80 % >130 mg/dl, 90% sensitivity at the cost of false positivity ADA and ACOG accept either Confirmation based on subsequent OGTT Screening…

33. Criteria Fasting One hour Two hour Three hour Diagnostic Criteria for GDM (100gm OGTT) 95 mg/dl 180 mg/dl 155 mg/dl 140 mg/dl 2 or more abnormal value (75gm OGTT) 92 mg/dl 180 mg/dl 153 mg/dl ----- One abnormal value Diagnostic criteria

34. Key elements: Achieving and maintaining excellent glycemic control Screening, monitoring , and intervention for: M aternal medical complications Fetal and obstetrical complications Options: Self blood glucose monitoring Dietary therapy Administration of insulin Treatment…

35. Glucose monitoring C ornerstone for achieving the set targets Fasting and Postprandial plasma glucose Four to six glucose measurements per day Treatment…

36. Timing GDM Pregesational DM HgbA1C <6% Before meals <95mg/dl 60 -99mg/dl 1hr after meal <140mg/dl 100-129mg/dl 2hr after meal <120mg/dl Glycemic targets during pregnancy

37. Diet: core management of hyperglycemia Additional 300 kcal/day required Medical Nutrition T herapy (MNT) The targets to be achieved by MNT: Provide sufficient nutrition to the mother and fetus Provide adequate calories for maternal weight gain Achieve normoglycemic state Prevent ketosis

38. 3 small to moderate meal and 2-4 snacks Carbohydrate: 40-50%, protein: <20 %, fats: 40% Snack: caloric needs, support for hypoglycemia, pre-pregnancy BMI Bedtime snacks: minimize nocturnal hypoglycemia MNT…

39. A djunct to MNT ACOG(2009): In the absence of complications , pregnant women exercise at a moderate level for: 20-45 minutes 3 times per week Daily walking, swimming or cycling for 30 min Exercise

40. Most validated treatment when MNT fails How long is a trail of MNT? Insulin therapy if diagnosis late in pregnancy For pregestational DM, the average insulin requirement: 0.7 units/kg in the first trimester 0.8 U/kg for weeks 13 to 28 0.9 U/kg for weeks 29 to 34 1.0 U/kg for weeks 35 to term Insulin therapy

41. P repregnant BMI and present pregnancy weight 2/3rd morning 2:1 ( basal:regular ) 1/3rd dinner and bedtime 1:1 ( regular:basal ) Total dose needs to be increased by 10-20 % every 3-7 days Intensively treated, multiple insulin injection: Better pregnancy outcome compared to conventional therapy Insulin…

42. Human insulin recommended by ADA Rapid acting analogues : lispro , aspart Long acting analogues: Not well studied i n pregnant woman Lispro and Aspart : pregnancy risk category B Oral hypoglycemic agents in pregnancy Glyburide and metformin have comparable effects as that of insulin Insulin…

43. Second trimester Detailed ultrasound examination of fetal anatomy at 18 weeks Maternal serum AFP Detailed multi-image echocardiography at 22 weeks Third trimester Continued close monitoring of maternal blood glucose levels Fetal testing and monitoring Monitoring for obstetrical or medical complications Obstetrical management

44. 32–34 weeks twice per week Testing at earlier gestational age: Daily fetal movement counting Doppler velocimetry of umbilical artery Vascular complications and poor fetal growth Antepartum fetal monitoring

45. ANC: E very two to four weeks: second trimester 1-2 weeks: third trimester Weekly after 36weeks Maternal surveillance At each visit: Achievement of targeted blood glucose levels Compliance to MNT and/or insulin therapy Regular blood pressure measurement Urinary protein

46. Optimal timing: controversial Amniocentesis before 39 week Well-controlled diabetes: E xpected date of delivery, antenatal testing reassuring ACOG: cesarean section for >4.5 kg Timing and mode of delivery

47. Goal: avoid maternal hyperglycemia T ype of diabetes and phase of labor Combination of glucose and insulin infusion ACOG: intrapartum glycemic control: 70 - 110 mg/dl Glucose monitoring: every hour during insulin infusion Labor and delivery

48. CESAREAN DELIVERY Schedule for early morning Take nighttime dose medication G lucose monitoring Postoperative glucose levels: Initially monitored every two hours until stable 5 % dextrose infusion

49. Insulin resistant state in pregnancy rapidly disappears Sliding scale for the first 24 to 48 hours Type 1 : one-third to one-half of their dose Type 2: may not require medication first 24 to 48 hours If they require insulin, 0.6 units/Kg postpartum weight Oral agents, metformin or glyburide C an be safely used while breastfeeding Postpartum follow up

50. Strongly encouraged to breastfeed Breastfeeding: additional 500 kcal per day Standard diabetes management resumed Glycemic targets: Postpartum… Glycated hemoglobin <7.0% Premeal <120mg/dl Two-hour postprandial <170mg/dl

51. ACOG , ADA: recommend long-term follow-up Recommendations: ( 1) Measurement of fasting plasma glucose annually (2) OGTT with 75g glucose at 6 week postpartum (3) Adequate contraception Postpartum follow-up

52. Any type of contraception Low dose estrogen-progestin oral contraceptives Progestin-only oral contraceptives Permanent methods Contraception