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 workshopconference 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
Carpenter- IADPSG
Coustan
( OGTT)*
criteria
( OGTT)**
( OGTT)**
105
95
92
190
180
180
165
155
153
145
140
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
>= 105 mg/dl or
2 hr
postprandial
<120 mg/dl
>= 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/m2
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
Total weight gain
(kg)
Underweight (<18.5
kg/m2)
Normal weight
(18.5-24.9 kg/m2)
Overweight (25.029.9 kg/m2)
Obese (>= 30.0
kg/m2)
12.5-18
Rates of weight
gain 2nd and 3rd
trimester (kg/wk)
0.51 (0.44-0.58)
11.5-16
0.42 (0.35-0.50)
7-11.5
0.28 (0.23-0.33)
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
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 longterm 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 shortacting 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
Test
Purpose
Postdelivery (1-3d)
Fasting or random PG
Detect presistent, overt
diabetes
Early postpartum (612wk)
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
Classification of the ADA 2003
Normal
Impaired
Diabetes
fasting glucose mellitus
or impaired
glucose
tolerance
Fasting < 110
mg/dl
2hr < 140 mg/dl
Fasting 110-125
mg/dl
2hr >= 140-199
mg/dl
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
Over 20
10-19
Before 10
< 10
10-19
> 20
F
R
Any
Any
Any
Any
H
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
Diabetic (%)
P value
28
Nondiabetic
(%)
9
Gestational
hypertension
Preterm birth
Macrosomia
28
45
5
13
<0.001
<0.001
Fetal growth
restriction
5
10
<0.001
Stillbirths
1.0
1.7
0.4
0.6
0.06
0.004
Perinatal
deaths
<0.001
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
Caudal regression
Ratio of incidence
252
Situs inversus
84
2
Spina bifida, hydrocephaly, or
other CNS defects
Anencephaly
Cardiac anomalies
Anal/rectal atresia
Renal anomalies
Renal agenesis
Cystic kidney
Duplex ureter
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 longterm 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, Bmimetic 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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