Piyawadee Wuttikonsammakit, M.D.
Jan 13, 2016
Piyawadee Wuttikonsammakit, M.D.
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
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
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
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
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
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
Criteria NDDG criteria
( OGTT)**
Carpenter-
Coustan criteria
( OGTT)**
IADPSG
( OGTT)*
Fasting 105 95 921 hr 190 180 1802 hr 165 155 1533 hr 145 140 -National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other
categories of glucose intolerance. Diabetes 1979; 28: 1039-57Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982; 144: 768-73American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2011; 34 (suppl1): S62-S69
Diagnosis Fasting 2 hour after loaded 75gm glucose
Diabetes >= 126 mg/d or
>= 200 mg/dl
Impaired glucose tolerance (IGT)
<126 mg/dl and
>= 140 and < 200 mg/dl
Impaired fasting glucose (IFG)
110-125 mg/dl and
<140
Fasting plasma glucose
2 hr postprandial
GDM A1 <105 mg/dl and
<120 mg/dl
GDM A2 >= 105 mg/dl or
>= 120 mg/dl
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
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
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
Diet Exercise Glucose monitoring Insulin
Average of 30 kcal/kg/d based on prepregnant body weight for nonobese women
30% caloric restriction for obese women with BMI > 30 kg/m2
Monitored with weekly tests for ketonuria
Maternal ketonemia linked with impair psychomotor development in offspring
Exercise improved cardiorespiratory fitness
Physical activity reduced risk of GDM Resistance exercise diminished the
need for insulin therapy in overweight women with GDM
Prepregnancy BMI
Total weight gain (kg)
Rates of weight gain 2nd and 3rd trimester (kg/wk)
Underweight (<18.5 kg/m2)
12.5-18 0.51 (0.44-0.58)
Normal weight (18.5-24.9 kg/m2)
11.5-16 0.42 (0.35-0.50)
Overweight (25.0-29.9 kg/m2)
7-11.5 0.28 (0.23-0.33)
Obese (>= 30.0 kg/m2)
5-9 0.22 (0.17-0.27)
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
Aim Fasting plasma glucose < 95 mg/dl 1 hr postprandial < 140 mg/dl 2 hr postprandial < 120 mg/dl
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
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
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
Rapid acting Short (regular) Intermediate Long acting
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
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
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
Labor evaluation Electronic fetal monitoring DTX q 1-2 hr Insulin iv drip Off insulin after delivery Newborn evaluation : birthweight,
APGAR score, hypoglycemia
Blood glucose (mg/dl)
Insulin dosage (unit/hour)
Fluids (125ml/hr)
<100 0 D5 (N/2 or LRS)
100-140 1.0 D5 (N/2 or LRS)
141-180 1.5 Normal saline181-220 2.0 Normal saline>220 2.5 Normal salineAmerican College of Obstetricians and Gynecologists. Pregestational diabetes Mellitus. ACOG Practice Bulletin 60. Washington, DC; ACOG; 2005
Time Test Purpose
Postdelivery (1-3d) Fasting or random PG
Detect presistent, overt diabetes
Early postpartum (6-12wk)
75 g 2-h OGTT Postpartum classification of glucose metabolism
1 yr postpartum 75 g 2-h OGTT Assess glucose metabolism
annually FPG Assess glucose metabolism
Tri-annually 75 g 2-h OGTT Assess glucose metabolism
Prepregnancy 75 g 2-h OGTT Classify glucose metabolism
Normal Impaired fasting glucose or impaired glucose tolerance
Diabetes mellitus
Fasting < 110 mg/dl
Fasting 110-125 mg/dl
Fasting >= 126 mg/dl
2hr < 140 mg/dl
2hr >= 140-199 mg/dl
2hr >= 200 mg/dl
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
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
Low-dose hormonal contraceptives may be used safely by women with recent GDM
Class Age of onset
Duration Vascular diasease
B Over 20 < 10 NoneC 10-19 10-19 NoneD Before 10 > 20 Benign
retinopathyF Any Any Nephropath
yR Any Any Proliferative
retinopathyH Any Any Heart
American Diabetes Association 2011
Pregestational-or overt-diabetes has a significant impact on pregnancy outcome
Related to degree of glycemic control, degree of underlying cardiovascular or renal disease
Factor Diabetic (%)
Nondiabetic (%)
P value
Gestational hypertension
28 9 <0.001
Preterm birth
28 5 <0.001
Macrosomia 45 13 <0.001
Fetal growth restriction
5 10 <0.001
Stillbirths 1.0 0.4 0.06
Perinatal deaths
1.7 0.6 0.004
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
Anomaly Ratio of incidence
Caudal regression 252
Situs inversus 84
Spina bifida, hydrocephaly, or other CNS defects
2
Anencephaly 3
Cardiac anomalies 4
Anal/rectal atresia 3
Renal anomalies 5
Renal agenesis 4
Cystic kidney 4
Duplex ureter 23
Caudal regression syndrome
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)
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
Respiratory distress syndrome : fetal lung maturation was delayed in diabetic pregnancies
Hypoglycemia Hypocalcemia Hyperbilirubinemia Polycythemia Hypertrophic cardiomyopathy Long-term cognitive development Inheritance of diabetes
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
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
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
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
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
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
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)
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
All types of infections : candida vulvovaginitis, urinary infection, respiratory tract infection, puerperal pelvic infection, wound infection
Renal infection was associated with increased preterm delivery
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
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
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
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
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
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