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Gestational Diabetes Mellitus Dr. R V S N Sarma., M.D., M.Sc., (Canada) Consultant Physician & Chest Specialist Visit us at: www.drsarma.in 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 GDM GDM Glucose Intolerance in Pregnancy Prevalence of GDM 3 to 18 % www.drsarma.in 3 GDM - Definition GDM • 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 Pathogenesis of GDM 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 1st phase insulin, Hyperinsulinemia • Islet cell auto antibodies (2 to 25% cases) • Glucokinase mutation in 5% of cases www.drsarma.in 5 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 Normal Glucose Tolerance GDM www.drsarma.in 7 Abnormal GT in GDM GDM www.drsarma.in 8 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 Adopted from ADA guidelines 9 Whom to Screen for GDM ? 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 www.drsarma.in Adopted from ADA guidelines 10 Indian Scenario GDM • 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 GDM – Two Step Screening GDM • 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 Glucose Challenge Test (GCT) GDM < 140 140 to 180 180+ No GDM repeat 24 wk Need to do OGTT – 3 hr GDM confirmed www.drsarma.in 13 Please be specific GDM • 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 OGTT –100g –3 hour Test GDM www.drsarma.in Test sample timing Plasma Glucose value Fasting (mg%) 95 1 hour (mg%) 180 2 hour (mg%) 155 3 hour (mg%) 140 15 Some Questions GDM 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 GDM – Fetal Morbidity GDM • • • • • • • • • 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 Macrosomia GDM • Birth weight > 4000 g - 90th 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 Macrosomic Newborn (4.2kg) GDM www.drsarma.in 19 Shoulder Dystocia GDM Erb’s palsy www.drsarma.in 20 Macrosomia GDM GDM Non DM P value Birth Weight 3512 g 3333 g < 0.05 LGA 40.4% 13.7% < 0.001 Macrosomia 32.0% 11.0% < 0.01 Neonatal Hypoglycemia GDM • 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 Minor Adverse Health Effects Normal Birth Wt (g) 3303±64 GDM GDM DM P 3649±51 3849±72 <0.01 Macrosomia(%) 8 36 47 <0.01 C-S 5 10 14 <0.01 Hypoglycemia 2 28 52 <0.01 Hypocalcemia 0 4 7 <0.01 Hyperbilirubinemia 15 23 21 <0.01 7 11 <0.01 Polycythemia 0 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 Major Adverse Health Effects Normal GDM DM CNS 6.4% 18.4% Congenital heart disease 7.5% 21.0% Respiratory disease 2.9% 7.9% Intestinal atresia 0.6% 2.6% Anal atresia 1.0% 2.6% Renal & Urinary defect 3.1% 11.8% Upper limb deficiencies 2.3% 3.9% Lower limb deficiencies 1.2% 6.6% Upper + Lower spine 0.1% 6.6% Caudal digenesis 0.1% 5.3% Neonatal Complications GDM DM GDM T. hypoglycemia(%) 52 28 3 <0.01 P. hypoglycemia(%) 6 2 0 <0.01 Hypocalcemia(%) 5 5 0 <0.01 Hyperbilirubinemia(%) 21 23 15 <0.01 5 2 0 <0.01 11 7 0 <0.01 RDS(%) 5 2 0 <0.01 IUGR(%) 2 1 0 <0.05 Trans tachypnea(%) Polycythemia(%) Normal p-value GDM Congenital Anomalies - DM Control Maternal HbA1c levels < 7.2 Nil 7.2-9.1 14% 9.2-11.1 23% > 11.2 25% Critical periods - 3-6 weeks post conception Need pre-conceptional metabolic care Late effects on the offspring GDM • Increased risk of IGT • Future risk of T2DM • Risk of Obesity www.drsarma.in 27 Maternal Morbidity GDM • 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 Risk of T2DM after GDM 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 A Delicate Balance ! GDM • 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 Women with T2DM GDM • 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 GDM – Glycemic Targets GDM Recommended values for Glycemic Targets Pre-pregnancy Hb A1c 7.00 (if possible 6.00) Pregnancy values Range FPG 1 hr PPG 100 – 140 2 hr PPG 90 – 120 Hb A1c www.drsarma.in 70 - 95 6.00 32 GDM and MNT • • • • • • • • • GDM 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 3rd 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 Diet therapy in GDM GDM • Small, frequent meals • Avoid eating for two • Avoid fasts and feasts • Avoid health drinks • Eat a bedtime snack Tips for diet management GDM • Small breakfast • Mid morning snack • High protein lunch • Mid afternoon snack • Usual dinner • Bed time snack GDM and Exercise GDM • 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 GDM and Insulins • • • • • • • • • GDM 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 Insulin Regimen GDM • 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. 1st 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 GDM and Delivery GDM • Delivery until 40 weeks is not recommended • Delivery before 39th 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 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 Punarapi Garbham Yet another conception Punarapi Prasavam GDM Yet another child-birth www.drsarma.in 41 Punarapi Jananee Once again for the mom Sisuvau KaTinam GDM and the babe, the miseries www.drsarma.in 42 Iha Madhu maehae This Diabetes you see Bahu Dustarae GDM Terrible to the core www.drsarma.in 43 Kripaya Nivaaare Please put an end to this Nipunarae vidyae GDM O! Doctor, the expert ! www.drsarma.in 44 Punarapi Jananam www.drsarma.in GDM 45