2. GDM Gestational Diabetes Mellitus Dr. R V S N Sarma., M.D., M.Sc., (Canada) Consultant Physician & Chest Specialist Visit us at: www.drsarma.inwww.drsarma.in

3. GDM Gestational Diabetes Mellitus Is it physiological? Is it a disease? Should we screen for gdm? Does it require treatment? Recent RCTs settled the issues Crowther et al. NEJM 2005;352

4. GDM Glucose Intolerance in Pregnancy www.drsarma.in 3 Prevalence of GDM 3 to 18 %

5. GDM GDM - Definition Distinguish GDM from Pre-gestational DM Abnormal Glucose Tolerance Onset (begins) with pregnancy or Detected first time during pregnancy No h/o of pre pregnancy DM or IGT Hb A 1 c is usually < 7.5 in GDM In DM + Pregnancy it is > 7.5 GDM is a forerunner of T2DM www.drsarma.in 4

6. GDM Pathogenesis of GDM Pregnancy is Diabetogenic condition A Wonderful Metabolic Stress Test Placental Diabetogenic Hormones –Progesterone, Cortisol, GH –Human Placental Lactogen (HPL), Prolactin Insulin Resistance (IR), ↑  cell stimulation Reduced Insulin Sensitivity up to 80% Impaired 1 st phase insulin, Hyperinsulinemia Islet cell auto antibodies (2 to 25% cases) Glucokinase mutation in 5% of cases www.drsarma.in 5

7. GDM Fundamental Defect in GDM The hormones of pregnancy cause IR They also cause direct hyperglycemia But, the basic defect is The maternal pancreatic  cells are unable to compensate for this increased demand www.drsarma.in 6

8. GDM Normal Glucose Tolerance www.drsarma.in 7

9. GDM Abnormal GT in GDM www.drsarma.in 8

10. GDM Risk Stratification for GDM High Risk Group (Indians mostly) –BMI  30; PCOD; Age > 35 years –F h/o DM; Ethnic predisposition; Acanthosis –Previous h/o GDM, IGT, Macrosomic baby Low Risk Group –Age < 25, BMI < 23, No F h/o DM or IGT –No bad obstetric history; No ↑ risk ethnicity Intermediate Risk Group –Not falling in the above two classes www.drsarma.in 9 Adopted from ADA guidelines

11. GDM 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 2 nd & 3 rd trimester www.drsarma.in 10 Adopted from ADA guidelines

12. GDM Indian Scenario Since the pregnant mothers without any of the risk factors are so very few in India Since we boast of being in the DM capitol We need to screen all pregnant women And identify early the GDM problem We have enough tough maternal problems Let us at least treat a treatable problem www.drsarma.in 11

13. GDM GDM – Two Step Screening Two Step Screening –Do a Random Glucose Challenge Test (GCT) –50 grams of oral glucose any time of day –1 hour post test for plasma glucose (1 hr PG) –Result > 180 mg% - Dx of GDM confirmed –Result > 140 mg% - Dx of GDM suspected –140 to 180 – We need OGTT (100 g) to confirm One Step Screening –OGTT – 3 hours after 100 g of oral glucose www.drsarma.in 12

14. GDM Glucose Challenge Test (GCT) < 140 No GDM repeat 24 wk 140 to 180 Need to do OGTT – 3 hr 180+ GDM confirmed www.drsarma.in 13

15. GDM Please be specific Do not use the ‘loose’ word ‘Blood Sugar’ Be specific to measure ‘Plasma Glucose’ Always venous sample for OGTT No capillary blood testing for OGTT NaF to be added as anticoagulant to blood Centrifuge to separate plasma immediately Plasma glucose to be estimated a.s.a.p Glucometer can be used for monitoring www.drsarma.in 14

16. GDM OGTT –100g –3 hour Test Test sample timingPlasma Glucose value Fasting (mg%)95 1 hour (mg%)180 2 hour (mg%)155 3 hour (mg%)140 www.drsarma.in 15

17. GDM Some Questions When to order for USG ? Scan for anomalies at 20-weeks Growth scans from 26-28 weeks Breast feed or not after delivery ? Must give breast feeding This reduces maternal glucose intolerance www.drsarma.in 16

18. GDM GDM – Fetal Morbidity Macrosomia of the baby CPD – Shoulder Dystocia Intrapartum Trauma – Feto-maternal Congenital Anomalies, HCM Neonatal Hypoglycemia Neonatal Hypocalcemia Neonatal Hyperbilirubinemia Respiratory Distress Syndrome (RDS) Polycythemia (secondary) in the new born www.drsarma.in 17

19. GDM Macrosomia Birth weight > 4000 g - 90 th percentile GA ↑ Intrapartum feto-maternal trauma Increased need for C- Section 20 – 30% of infants of GDM – Macrosomic Maternal factors for Macrosomia –Uncontrolled Hyperglycemia –Particularly postprandial hyperglycemia –High BMI of mother –Older maternal age, Multiparity www.drsarma.in 18

20. GDM Macrosomic Newborn (4.2kg) www.drsarma.in 19

21. GDM Shoulder Dystocia www.drsarma.in 20 Erb’s palsy

22. GDM Macrosomia GDMNon DMP value Birth Weight3512 g3333 g< 0.05 LGA40.4%13.7%< 0.001 Macrosomia32.0%11.0%< 0.01

23. GDM Neonatal Hypoglycemia Due to fetal hyperinsulinemia Neonatal plasma glucose < 30 mg% Poor glycemic control before delivery Increases perinatal morbidity Congenital anomalies – 3 to 8 times more More if periconception hyperglycemia Assoc. maternal fasting hyperglycemia www.drsarma.in 22

24. GDM Minor Adverse Health Effects Birth Wt (g)3303±643649±51 3849±72 <0.01 Macrosomia(%)83647<0.01 C-S 51014<0.01 Hypoglycemia 22852<0.01 Hypocalcemia 0 4 7<0.01 Hyperbilirubinemia152321<0.01 Polycythemia 0 711<0.01 Cord C-Pep 1.18±0.1 2.07±0.12 2.98±0.22 <0.01 Cord Glu 100±3.6 103±2.9 114±5.5 <0.01 NormalGDMDMP

25. GDM CNS6.4%18.4% Congenital heart disease7.5%21.0% Respiratory disease2.9%7.9% Intestinal atresia0.6%2.6% Anal atresia1.0%2.6% Renal & Urinary defect3.1%11.8% Upper limb deficiencies2.3%3.9% Lower limb deficiencies1.2%6.6% Upper + Lower spine0.1%6.6% Caudal digenesis0.1%5.3% Normal DM Major Adverse Health Effects

26. GDM Neonatal Complications T. hypoglycemia(%) 5228 3<0.01 P. hypoglycemia(%) 6 2 0<0.01 Hypocalcemia(%) 5 5 0<0.01 Hyperbilirubinemia(%) 212315<0.01 Trans tachypnea(%) 5 2 0<0.01 Polycythemia(%) 11 7 0<0.01 RDS(%) 5 2 0<0.01 IUGR(%) 2 1 0<0.05 DM GDM Normal p-value

27. GDM Congenital Anomalies - DM Control Maternal HbA1c levels < 7.2Nil 7.2-9.114% 9.2-11.123% > 11.225% Critical periods - 3-6 weeks post conception Need pre-conceptional metabolic care

28. GDM Late effects on the offspring Increased risk of IGT Future risk of T2DM Risk of Obesity www.drsarma.in 27

29. GDM Maternal Morbidity Hypertension; Insulin Resistance Preeclampsia and Eclampsia Cesarean delivery; Pre term labour Polyhydramnios – fluid > 2000 ml Post-partum uterine atony Abruptio placenta www.drsarma.in 28

30. GDM Risk of T2DM after GDM IGT and T2DM after delivery in 40% of GDM R.R of T2DM for all with GDM is 6 (C.I. 4.1 – 8.8) Must be counseled for healthy life style Re-evaluate with 75 g OGTT after 6 wk, 6 months More risk - if GDM before 24 wks of gestation High levels of hyperglycemia during pregnancy If the mother is obese and has +ve family h/o GDM in previous pregnancies and age > 35 yrs. High risk ethnic group (like Indians) www.drsarma.in 29

31. GDM A Delicate Balance ! Plasma Glucose values in pregnancy hang on a delicate balance If the Mean Plasma Glucose (MPG) is –Less than 87 mg% - IUGR of fetus –More than 104 mg% - LGA of fetus It is imp. to screen for hypothyroidism www.drsarma.in 30

32. GDM Women with T2DM T2DM patients must plan their pregnancy Preconception Hb A1c  7.00; MAU estimate OADs should be discontinued; Folic acid + Start on Insulin and titrate for euglycemia Nutrition and weight gain counseling ACEi and ARB must be substituted Screening for retinopathy; nephro (eGFR <90) Must avoid hypoglycemia and ketosis SMBG must be trained and started www.drsarma.in 31

33. GDM GDM – Glycemic Targets Recommended values forGlycemic Targets Pre-pregnancy Hb A1c  7.00 (if possible  6.00) Pregnancy valuesRange FPG70 - 95 1 hr PPG100 – 140 2 hr PPG90 – 120 Hb A1c  6.00 www.drsarma.in 32

34. GDM GDM and MNT Two weeks trial of Medical Nutrition Therapy Pre-pregnancy BMI is a predictor of the efficacy If target glycemia is not achieved initiate insulin MNT – extra 300 calories in 2 and 3 rd trimesters Calories – 30 kcal/kg/day = 1800 kcal for 60 kg If BMI > 30; then only 25 kcal/kg/day 3 meals and 3 snacks – avoid hypoglycemia 50% of total calories as CHO, 25% protein & fat Low glycemic, complex CHO, fiber rich foods www.drsarma.in 33

35. GDM Diet therapy in GDM Small, frequent meals Avoid eating for two Avoid fasts and feasts Avoid health drinks Eat a bedtime snack

36. GDM Tips for diet management Small breakfast Mid morning snack High protein lunch Mid afternoon snack Usual dinner Bed time snack

37. GDM GDM and Exercise Recumbent bicycle Upper body egometric exercises Moderate exercises Mother to palpate for uterine contractions Walking is the simplest and easiest Continue pre pregnancy activity Do not start new vigorous exercise www.drsarma.in 36

38. GDM GDM and Insulins In 10 to 15% of GDM, MNT fails –Start on insulin Good glycemic control – No increased risk Human Insulins only – Not Analogs Daily SMBG up to 7 times! Insulin Glargine (Lantus) – Not to be used at all Insulin Lispro tested and does not cross placenta Insulin Aspart not evaluated for safty CSII may be needed in some cases Oral drugs not recommended (SU?, Metformin?) www.drsarma.in 37

39. GDM Insulin Regimen If MNT fails after 2 - 4 weeks of trial Initiate Insulin + Continue MNT Dose: 0.7, 0.8 and 0.9 u/kg – 1, 2 & 3 trim. Eg. 1 st trim – 64 kg = 0.7 x 64 = 45 units Give 2/3 before BF = 30 units of 30:70 mix Give 1/3 before supper = 15 u of 50:50 mix Increase total dose by 2-4 units based on BG After BG levels stabilize – monitor till term www.drsarma.in 38

40. GDM GDM and Delivery Delivery until 40 weeks is not recommended Delivery before 39 th week – assess the pulmonary maturity by phosphatase test on amniocentesis fluid C - Section may be needed (25 -30%) Be prepared for the neonatal complications Assess the mother after delivery for glycemia May need to continue insulin for a few days Pre-gestational DM–Insulin (30% less) or OAD www.drsarma.in 39

41. punarapi jananam punarapi maranam Once again is the birth, sure follows the death punarapi jananee jaTarae sayanam | Yet again, is the slumber in the uterine filth iha samsaarae bahu dustaarae he! what to say of this miserable troth kripayaa paarae paahi muraarae || O! lord, save us from this cyclical myth Jagad Guru Adi Sankaracharya’s Bhaja Govindam

42. GDM Punarapi Garbham Yet another conception www.drsarma.in 41 Punarapi Prasavam Yet another child-birth

43. GDM Punarapi Jananee Once again for the mom www.drsarma.in 42 Sisuvau KaTinam and the babe, the miseries

44. GDM Iha Madhu maehae This Diabetes you see www.drsarma.in 43 Bahu Dustarae Terrible to the core

45. GDM Kripaya Nivaaare Please put an end to this www.drsarma.in 44 Nipunarae vidyae O! Doctor, the expert !

46. GDM Punarapi Jananam www.drsarma.in 45