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