Gestational diabetes mellitus

Piyawadee Wuttikonsammakit, M.D.

GDM

 Prevalence of diagnosed diabetes has increased : 14.5 (1991)  47.9 cases/1000 (2003)  Increasing prevalence of type 2 diabetes in younger people  Maternal hyperglycemia leads to fetal hyperinsulinemia, obesity & insulin resistance in childhood

GDM

 Defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy  Some women with GDM have previously unrecognized overt diabetes  Fasting hyperglycemia early in pregnancy almost invariably represents overt diabetes

Screening

 No consensus regarding the optimal approach  Universal or selective screening  Plasma glucose after 50 g glucose test (50 gm glucose challenge test –GCT) is the best to identify women at risk for GDM  One-step approach or two-step approach

Fifth international workshop conference on gestational diabetes

 Low risk : blood glucose testing not routinely required if all the following are present:        Member of an ethnic group with a low prevalence of GDM No known diabetes in first-degree relatives Age < 25 years Weight normal before pregnancy Weight normal at birth No history of abnormal glucose metabolism No history of poor obstetrical outcome

GDM screening

 Average risk : perform blood glucose testing at 24-28 weeks using either :  Two-step procedure : 50-g GCT, followed by a diagnostic 100-g OGTT  One-step procedure : diagnostic 100-g OGTT performed on all subjects

GDM screening

  High risk : Perform blood glucose testing as soon as feasible, suing the procedures described above if one or more of these are present :  Severe obesity   Strong family history of type 2 diabetes Previous history of GDM, impaired glucose metabolism, or glucosuria If GDM is not diagnosed, blood glucose testing should be repeated at 24-28 weeks or at any time there are symptoms or signs suggestive of hyperglycemia

Diagnosis

Criteria

Fasting 1 hr 2 hr 3 hr

NDDG criteria ( OGTT)**

105 190 165 145

Carpenter Coustan criteria ( OGTT)**

95 180 155 140

IADPSG ( OGTT)*

92 180 153 National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 28: 1039-57 Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982; 144: 768-73 American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2011; 34 (suppl1): S62-S69

WHO criteria diagnosis

Diagnosis Fasting

Diabetes Impaired glucose tolerance (IGT) Impaired fasting glucose (IFG) >= 126 mg/d or <126 mg/dl and 110-125 mg/dl

and 2 hour after loaded 75gm glucose

>= 200 mg/dl >= 140 and < 200 mg/dl <140

GDM

GDM A1 GDM A2

Fasting plasma glucose

<105 mg/dl and

2 hr postprandial

<120 mg/dl >= 105 mg/dl or >= 120 mg/dl

Maternal and fetal effects

    Fetal anomalies are not increased Risk of fetal death is not apparent for those who have diet-treated postprandial hyperglycemia Elevated fasting glucose levels have increased rates of unexplained stillbirths during the last 4-8 weeks of gestation Increased frequency of hypertension and cesarean delivery

Macrosomia

    ACOG 2000 : birthweight exceeds 4500 g Anthropometrically different from other LGA infants : excessive fat deposition on the shoulders and trunk Predisposes to shoulder dystocia or cesarean delivery Maternal hyperglycemia prompts fetal hyperinsulinemia during second half of gestation, which in turn stimulates excessive somatic growth

Macrosomia and Erb’s palsy

Macrosomia

 Neonatal hyperinsulinemia may provoke hypoglycemia (<35 mg/dl) within minutes of birth  Maternal obesity is an independent and more important risk factor for large infants in women with GDM than is glucose intolerance  Maternal obesity is an important confounding factor in the diagnosis of GDM

Management

 Diet  Exercise  Glucose monitoring  Insulin

Diet

 Average of 30 kcal/kg/d based on prepregnant body weight for nonobese women  30% caloric restriction for obese women with BMI > 30 kg/m 2  Monitored with weekly tests for ketonuria  Maternal ketonemia linked with impair psychomotor development in offspring

Exercise

 Exercise improved cardiorespiratory fitness  Physical activity reduced risk of GDM  Resistance exercise diminished the need for insulin therapy in overweight women with GDM

Body weight control

Prepregnancy BMI

Underweight (<18.5 kg/m2)

Total weight gain (kg)

12.5-18

Rates of weight gain 2 nd and 3 rd trimester (kg/wk)

0.51 (0.44-0.58) Normal weight (18.5-24.9 kg/m2) Overweight (25.0 11.5-16 7-11.5

0.42 (0.35-0.50) 0.28 (0.23-0.33) 29.9 kg/m2) Obese (>= 30.0 5-9 0.22 (0.17-0.27) kg/m2) Rasmussen KM, Yaktine Al. Weight gain during pregnancy: reexamining the guildelines. Washington: Committee to Reexamine IOM Pregnancy Weight Guidelines; Institute of Medicine; National Research Council 2009: 254

Glucose monitoring

 Aim  Fasting plasma glucose < 95 mg/dl  1 hr postprandial < 140 mg/dl  2 hr postprandial < 120 mg/dl

Glucose monitoring

 Daily self glucose monitor VS intermittent fasting glucose evaluation semiweekly : fewer macrosomic infants and gain less weight in diet-treated GDM  The women with GDM A2 : 1hour postprandial blood glucose superior to preprandial : fewer neonatal hypoglycemia, less macrosomia, fewer CS for dystocia

Oral hypoglycemic agents

    ACOG 2001 has not recommended these agents during pregnancy Half of maternal concentration in women treated with glyburide Increasing support use of glyburide as an alternative to insulin in GDM Meta-analysis 2008 : no increased perinatal risks with glyburide therapy and recommended further randomized trials

Metformin

 The Fifth International workshop conference recommended that metformin treatment for GDM be limited to clinical trials with long term infant follow up  RCT 2008 : metformin VS insulin : not associated with increased perinatal complications, but 46% required supplemental insulin

Insulin therapy

    Rapid acting Short (regular) Intermediate Long acting

Insulin acting

Insulin therapy

 Initiate insulin if fasting glucose levels > 105 mg/dl  Total dose of 20-30 units daily  Before breakfast is commonly used to initiate therapy  Split-dose insulin (twice daily) : divided into 2/3 intermediate-acting and a third short acting insulin

Obstetrical management

   ACOG 2001 has suggested that CS delivery should be considered in women with a sonographically EFW >= 4500 Elective induction to prevent shoulder dystocia in women with sonographically diagnosed fetal macrosomia is controversial Sonographic suspicion of macrosomia was too inaccurate to recommend induction or primary CS delivery without a trial of labor

Obstetrical management

 No consensus regarding whether antepartum fetal testing is necessary, and if so, when to begin such testing in women without severe hyperglycemia  Those women who require insulin therapy for fasting hyperglycemia, typically undergo fetal testing and are managed as if they had overt diabetes

Intrapartum management

 Labor evaluation  Electronic fetal monitoring  DTX q 1-2 hr  Insulin iv drip  Off insulin after delivery  Newborn evaluation : birthweight, APGAR score, hypoglycemia

Insulin IV drip

Blood glucose (mg/dl)

<100 100-140 141-180 181-220 >220

Insulin dosage (unit/hour)

0 1.0

1.5

2.0

2.5

Fluids (125ml/hr)

D5 (N/2 or LRS) D5 (N/2 or LRS) Normal saline Normal saline Normal saline American College of Obstetricians and Gynecologists. Pregestational diabetes Mellitus. ACOG Practice Bulletin 60. Washington, DC; ACOG; 2005

Postpartum evaluation : Fifth international workshop-conference

Time

Postdelivery (1-3d) Early postpartum (6 12wk) 1 yr postpartum annually Tri-annually Prepregnancy

Test

Fasting or random PG 75 g 2-h OGTT 75 g 2-h OGTT FPG 75 g 2-h OGTT 75 g 2-h OGTT

Purpose

Detect presistent, overt diabetes Postpartum classification of glucose metabolism Assess glucose metabolism Assess glucose metabolism Assess glucose metabolism Classify glucose metabolism

Classification of the ADA 2003

Normal

Fasting < 110 mg/dl 2hr < 140 mg/dl

Impaired fasting glucose or impaired glucose tolerance

Fasting 110-125 mg/dl 2hr >= 140-199 mg/dl

Diabetes mellitus

Fasting >= 126 mg/dl 2hr >= 200 mg/dl

Postpartum evaluation

    33-37% underwent postpartum screening tests Recommendations for postpartum follow-up are based on the 50% likelihood of women with GDM developing overt diabetes within 20 years If fasting hyperglycemia develops during pregnancy, then diabetes is more likely to persist postpartum Insulin therapy during pregnancy, and especially before 24 weeks , is a powerful predictor of persistent diabetes

Postpartum evaluation

    Women with Hx of GDM are also at risk for cardiovascular complications associated with dyslipidemia, hypertension, abdominal obesity – the metabolic syndrome Recurrence of GDM in subsequent pregnancies was documented in 40% Obese women were more likely to have impaired glucose tolerance Lifestyle behavioral changes : weight control and exercise

Contraception

 Low-dose hormonal contraceptives may be used safely by women with recent GDM

Pregestational diabetes mellitus

White classification

Class Age of onset Duration

B C D F R H Over 20 10-19 Before 10 Any Any Any < 10 10-19 > 20 Any Any Any

Vascular diasease

None None Benign retinopathy Nephropathy Proliferative retinopathy Heart

Diagnosis of overt diabetes during pregnancy

American Diabetes Association 2011

Pregestational diabetes

 Pregestational-or overt-diabetes has a significant impact on pregnancy outcome  Related to degree of glycemic control, degree of underlying cardiovascular or renal disease

Pregnancy outcomes

Factor

Gestational hypertension Preterm birth Macrosomia Fetal growth restriction Stillbirths Perinatal deaths

Diabetic (%) Nondiabetic (%)

28 28 45 5 1.0

1.7

9 5 13 10 0.4

0.6

P value

<0.001

<0.001

<0.001

<0.001

0.06

0.004

Fetal effects

    Improved fetal surveillance, neonatal intensive care, and maternal metabolic control have reduced perinatal losses to 2-4% Two major causes of fetal death : congenital malformations and unexplained fetal death Incidence of major malformations in women with type 1 diabetes is approximately 5% Hyperglycemia-induced oxidative stress that inhibits expression of cardiac neural crest migration

Congenital malformations in infants of women with overt diabetes

Anomaly Ratio of incidence

Caudal regression Situs inversus Spina bifida, hydrocephaly, or other CNS defects Anencephaly Cardiac anomalies Anal/rectal atresia Renal anomalies Renal agenesis Cystic kidney Duplex ureter 252 84 2 3 4 3 5 4 4 23

Caudal regression syndrome

Pregestational DM

 Early abortion is associated with poor glycemic control (HbA1c > 12%, persistent preprandial > 120 mg/dl)  Increased preterm delivery (both spontaneous & indicated)  Macrosomia and hydramnios  IUGR (advanced vascular disease or congenital malformations)

Unexplained fetal demise

    Stillbirths without identifiable causes are a phenomenon relatively unique to pregnancies complicated by overt diabetes.

No obvious placental insufficiency, abruption, FGR, or oligohydramnios Typically large-for-gestational age and die before labor, usually at 35 weeks or later Hyperglycemia-mediated chronic abberations in transport of oxygen and fetal metabolites

Neonatal mortality and morbidity

        Respiratory distress syndrome : fetal lung maturation was delayed in diabetic pregnancies Hypoglycemia Hypocalcemia Hyperbilirubinemia Polycythemia Hypertrophic cardiomyopathy Long-term cognitive development Inheritance of diabetes

Maternal effects

 Exception of diabetic retinopathy,, the long term course of diabetes is not affected by pregnancy  Maternal death is uncommon, rates are still increased tenfold  Deaths most often result from ketoacidosis, hypertension, preeclampsia, pyelonephritis, ischemic heart disease

Diabetic nephropathy

     3 stages 1. microalbuminuria – 30 to 300 mg of albumin/24h : manifest as early as 5 years after onset of diabetes 2. overt proteinuria – >300 mg/24hr (may develop hypertension) : develop after another 5 to 10 years 3. end-stage renal disease- rising creatinine, decreased GFR : develop in next 5 to 10 years PGDM class F significantly increased preeclampsia and indicated preterm delivery

Diabetic retinopathy

   The first and most common visible lesions are small microaneurysms followed by blot hemorrhages, hard exudates – benign or nonproliferative retinopathy Abnormal vessels on background eye disease become occluded, leading to retinal ischemia and infarctions “cotton wool exudate” – preproliferative retinopathy Neovascularization (in response to ischemia) on retinal surface and out into vitreous cavity and hemorrhage – proliferative retinopathy

Diabetic retinopathy

Diabetic retinopathy

 The effects of pregnancy on proliferative retinopathy are controversial  Laser photocoagulation and good glycemic control during pregnancy minimize the potential for deleterious effects of pregnancy

Diabetic neuropathy

 Peripheral symmetrical sensorimotor diabetic neuropathy is uncommon  Diabetic gastropathy, is trouble some in pregnancy causes N/V, nutritional problems, and difficulty with glucose control  Treatment : metoclopradmide and H2 receptor antagonists

Preeclampsia

  Risk factors for preeclampsia include any vascular complications and preexisting proteinuria, with or without chronic hypertension Risk of preeclampsia     11-12% in Class B, 21-22% in class C, 21-23% in class D, 36-54% in class F-R

Diabetic ketoacidosis

     Only 1% Most serious complication May develop with hyperemesis gravidarum, B mimetic drugs given for tocolysis, infection and corticosteroids Fetal loss is about 20% Pregnant women usually have ketoacidosis with lower blood glucose levels than when nonpregnant (293 mg/dl VS 495 mg/dl)

Management of ketoacidosis during pregnancy

     ABG, serum ketone, electrolyte, blood glucose q 1-2 hr Insulin IV infusion : loading 0.2-0.4 u/kg, maintenance 2-10 U/h Fluids : NSS 1 L in first hour, 500-1000ml/h for 2-4 h, 250 ml/h until 80% replaced Begin 5%D/NSS when glucose plasma level reaches 250 mg/dl Correct electrolyte : K, bicarbonate

Infection

 All types of infections : candida vulvovaginitis, urinary infection, respiratory tract infection, puerperal pelvic infection, wound infection  Renal infection was associated with increased preterm delivery

Management : preconceptional care

     Optimal preconceptional glucose control using insulin Preprandial 70-100 mg/dl, 1hr postprandial < 140 mg/dl, 2 hr < 120 mg/dl Hb A1c within or near the upper limit of normal (<6%) Most significant risk for malformation with levels > 10% Periconceptional folic acid 400 ug/d

Management : insulin

 OHD are not recommended for overt diabetes  Glycemic control usually achieve with multiple daily insulin injections and adjustment of dietary intake  Self-monitoring of capillary glucose levels using a glucometer is recommended

Diabetic diet

 A caloric intake of 30-35 kcal/kg/d (for normal weight women)  Three meals and three snacks daily  Underweight women : 40 kcal/kg/d  For those > 120% above ideal weight : 24 kcal/d  55% carbohydrate : 20% protein : 25% fat

Obstetric care

      Accurate dating Second trimester : targeted sonographic 18-20 weeks to detect NTD and other anomalies Third trimester : follow growth & fetal surveillance Caution : detection of fetal anomalies in obese women is more difficult Avoid hypoglycemia and hyperglycemia Increased insulin requirement after approximately 24 weeks

Obstetric care

     Increase CS delivery rate Delete the dose of long-acting insulin given on the day of delivery Insulin requirements typically drop markedly after delivery Insulin calibrated pump is most satisfactory It is not unusual to require no insulin for the first 24 hours or so postpartum and then fluctuate during the next few days

Contraception

 No single contraceptive method appropriate for all women with diabetes  Risk of vascular disease in hormonal contraceptives may be problematic  IUD increased risk of pelvic infection  Elect sterilization is an option

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