M.

Ilham Kosman

Gestational Diabetes
 Metabolic disorder of multiple etiology characterized by chronic
hyperglycemia with disturbances of carbohydrate, fat and protein
metabolism resulting from defects in insulin secretion, insulin
action, or both.

2000: 171 million  2030: 366 million.

1: World Health Organization. Prevention of diabetes mellitus. Report of a WHO Study Group. Geneva: World Health Organization; 1994. No. 844.
2: Hunt KJ, Schuller KL. The increasing prevalence of diabetes in pregnancy. Obstet Gynecol Clin North Am 2007; 34 (2): 173-99, vii.
Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005
 Pathogenesis of Type I DM
Environment

Genetic
Autoimmune

ß cell
Destruction

Type I / IDDM Insulin deficiency

 Pathogenesis of Type II DM
Genetic /
ß cell defect
Insulin Resistance

Relative
Insulin Def.
IDDM

ß cell
exhaustion
Type II NIDDM
Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005
 Gestational Diabetes Mellitus

• Diabetes diagnosed in the second or third trimester of

pregnancy that is not clearly either type 1 or type 2 diabetes
• Women with diabetes in the first trimester would be classified
as having type 2 diabetes.

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

 Diagnosis and Detection of GDM

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2011;34(suppl 1):S15.
Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005
 Glycosylated hemoglobin

• Major component of HbA1 is HbA1c – glucose added to the N-

terminal valine of the -chain.
• Amount of HbA1c correlates with the average blood glucose
concentration over the previous 2 - 3 months.
• In diabetic patients HbA1c give a good indication of blood
glucose control and have been correlated with long-term
complications of diabetes and with fetal outcome in pregnant
patients with diabetes.
 Error Interpretations
• Hb structural variants (HbS, HbC, or HbE); Hb synthesis
variants (β-thalassemia); and/or posttranslational
modifications of Hb (Schiff base, carbamylated Hb, or
acetylated Hb).
• Increased red blood cell turnover and shortened exposure to
glucose (occult bleeding and blood transfusion).
• Processes that lengthen red blood cell survival, such as iron
deficiency anemias.
 Correlation of A1C with
Estimated Average Glucose (eAG)
Mean plasma
glucose
A1C (%) mg/dl mmol/l
6 126 7.0
10
7 154 8.6 9
8

8 183 10.2 7
6

% HbA1c
9 212 11.8 5
4
3
10 240 13.4 2
1
11 269 14.9 0
0 2 4 6 8 10 12 14
Blood glucose concentration
12 298 16.5

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S18. Table 9.

 Risk Factors

• Physical inactivity • Hypertension/on therapy

• First-degree relative with • HDL < 35 mg/dL and/or
diabetes triglyceride > 250 mg
• High-risk race/ethnicity • PCOS
(African American, Latino, Native • A1C ≥ 5.7%, IGT, or IFG on
American, Asian American, Pacific previous testing
Islander). • Other clinical conditions
• Previous macrosomia infant (>9 associated with insulin
lb) or previous gestational resistace (severe obesity,
diabetes achantosis nigricans)
• History of CVD

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

 Early - Mid
Gestation

Late Gestation
International Journal of Reproductive Medicine Volume 2014, Article ID 797681, 14 pages
http://dx.doi.org/10.1155/2014/797681
HPL and human placental GH reduce insulin receptor sites and glucose
transport in insulin-sensitive tissues, stimulates maternal lypolisis. This
is called insulin resistance and usually starts about midway (20-40 weeks)
through pregnancy.

Normal

Insulin resistance- caused hyperglycemia from the HPL

 The preventative effects of exercise appear to extend to the
prevention of gestational diabetes mellitus (GDM)

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

 • Women with a history of GDM, metformin and intensive
lifestyle modification led to an equivalent 50% reduction in
diabetes risk, and both interventions remained highly
effective during a 10-year follow-up period.
• Metformin may be recommended for high-risk individuals
(e.g., those with a history of GDM, those who are very obese,
and/or those with more severe or progressive hyperglycemia)
and/or those with rising A1C despite lifestyle intervention.

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

 Effect in maternal
• Maternal mortality (60 deaths/100,000 pregnancies)
• Increased risk of C section (44%)
• Gestational hypertension and preeclampsia (12,7%)
• Infections
• Preterm delivery (32%)
• Post partum hemorrhage
• Obesity
• Risk of type 2 Diabetes in later life
Infant of a
Diabetic
Mother
Review of Newborn Implications
 Neonatal Complications
• Congenital • Metabolic
anomalies abnormalities
• Prematurity • Polycythemia
• Perinatal asphyxia • Low iron stores
• Macrosomia • Hyperbilirubinemia
• Respiratory distress • Cardiomyopathy
 “Fetopathy”
• Caused by
Chronic fetal increased
hyperinsulinemia metabolic
demands

O2 consumption, • Caused by
fetal hypoxemia, placental
erythropoiesis insufficiency

Polycythemia • Fetal
- ?HTN and Complicatio
cardiac n- still
birth
hypertrophy
 Neonatal Complications
• Perinatal Asphyxia
• Increased metabolic rate,
leading to increased oxygen
consumption and fetal
hypoxemia, as placenta
cannot keep up with demands.
• Macrocomia can make
delivery difficult, increased
risk of shoulder dystocia.
• Cardiomyopathy leading to
abnormalities in fetal heart
rate.
• Macrosomia
• Maternal elevated sugars cause
increased growth of the fetus,
especially in insulin sensitive
tissues (SQ fat, cardiac
muscle, liver).
• Elevated insulin levels in the
fetus stimulates glycogen
storage in the liver, increased
lipid synthesis, and
accumulation of fat.
• Infants have bigger head:chest
and shoulder:head ratios,
more body fat, and
visceromegaly.
• Disproportionate macrosomia
increases the risk of
hyperbilirubinemia,
hypoglycemia, metabolic
acidosis, and respiratory
distress.
 Neonatal Complications
• Respiratory Distress
• Common complication in
infants born to diabetic
mothers because maternal
hyperglycemia delays
surfactant synthesis and can
lead to impaired or delayed
lung maturation.
• Increased risk of neonatal
respiratory distress syndrome
• 2-3 times more likely to have
Transient Tachypnea of the
Newborn (TTN)
• Hypothesized to be caused
by delayed fluid clearance
in the diabetic fetal lung
• C-sections more common in
this population which also
increases risk of TTN
• Metabolic Abnormalities
• Hypoglycemia
• Defined as BG <40, onset
usually within the first few
hours of birth
• Commonly occurs in
macrosomic infants because
of continued
hyperinsulinemia even after
being removed from their
intrauterine glucose supply,
even 2-4 days.
• Strict maternal glucose
control can reduce the risk
but does not eliminate the
possibility of hypoglycemia
in the newborn.
• SGA infants also at risk
because of decreased
glycogen stores and
hyperinsulinemia decreases
the ability to mobilize
hepatic glycogen.
Neonatal Complications:
Metabolic Abnormalities
• Hypocalcemia • Hypomagnesemia
• Serum Ca <7mg/dL • Serum Mg level <1.5/dL
• Occurs in 5-30% in IDMs • 40% of IDMs within the
first 3 days after birth.
• Good maternal glycemic
control reduces risk • Thought to be due to low
maternal levels from
• Infants usually urinary loss secondary to
asymptomatic and diabetes.
resolves without
treatment, therefore • Usually transient and
routine screening not asymptomatic therefore
recommended. no need to screen unless
clinical concern.
• Consider measuring in
symptomatic infants:
jittery, apnea,
tachypnea, lethargy,
seizures.
 Neonatal Complications
• Polycythemia • Low iron stores
• Increased
erythropoietin
concentrations caused
by chronic fetal
hypoxemia
• Polycythemia can lead
to hyperviscosity
syndrome and vascular
sludging (if severe can
cause ischemia and
infarction or organs)
• Check hematocrit
within 12 hours of
birth
• One study showed 17%
on IDMs had Hcts> 60
and 5% >65
• Inversely related to
degree of polycythemia.
• With hypoxemia, fetus
has increased red cell
mass, which causes iron
redistribution, leading to
iron deficiency in
developing fetal organs
 cardiomyopathy,
neurodevelopmental
problems, etc.
• As extra red cells are
eventually broken down,
the iron will be
recirculated, so
supplementation is not
necessary.
 Neonatal Complications
• Hyperbilirubinemia • Cardiomyopathy
• 11-29% of IDMs
• Associated with
prematurity, poor maternal
glycemic control,
macrosomia and
polycythemia
• Increased risk of transient
cardiomyopathy thought to
be caused by fetal
hyperinsulinemia increasing
the synthesis and deposition
of fat and glycogen in
myocardial cells.
• Decreases size of ventricles,
possibly obstructing outflow
of the left ventricle.
• Infants with
cardiomyopathy are often
asymptomatic, however 5-
10% will have respiratory
distress or signs of poor
cardiac output.
• Congestive cardiomyopathy
rare.
 Effect in fetal
Maternal Fetal
Hyperglycemia Hyperglycemia
Pancreas stimulation
In utero programming Hyperplasia fetal islet
cell
Miscarriage
Congenital anomalies
Hyperinsulinemia
Hypoxemia
Metablic Acidosis BMR
Fetal Death increased
Macrosomia
Polycythemia and blood
hyperviscosity Fetal Oxygenation and
Hyperbilirubinemia erythropoiesis
Hypocalcemia
RDS
 Anatomic Fetal Monitoring
• First trimester ultrasound examination
• Nuchal translucency at 12–13 weeks
• Fetal morphology should be offered at 18–20 weeks
• Repeat morphology scanning at 24 weeks
• Fetal growth
 GDM and congenital anomalies
• A fourfold higher rate of congenital anomalies of the brain, heart,
kidneys, intestine, and skeleton.
• Prediction by maternal hemoglobin A1c values at 14 weeks’ gestation.
 < 7% have no greater risk
 Between 7% and 8.5%, the risk is 5%
 > 10% the risk rises to 22%
 Kenapa terjadi delay pamatangan paru ?

cadangan gula( glikogen), gula darah bebas, asam lemak dan insulin
memiliki efek Inhibisi atau menghambat langsung dalam sintesis
phospolipid
• PC : phospatidilcoline
• PG : Phospatinilgliserol
• DSPC : disaturated phospatidilcoline

Berakibat defisiensi surfaktan phospolipid  RDS

 Mechanisms
Embryonic hyperglycemia Excessive oxygen radicals in susceptible fetal tissues

Disrupt the vascularization Inhibitors of prostacyclin and overabundance of

of developing tissues. thromboxanes and other prostaglandins
 IUGR or Fetal Obesity?
IUGR Fetal Obesity
• Underlying vascular disease • Maternal glucose
• Maternal hypertension concentrations
• Higher incidence of structural • Fetal insulin concentrations
anomaly • Growth factors: IGF1 or IGF2
• Maternal obesity
 Bayi meninggal pada DMG

There are a number of pathophysiologic changes that have been

suggested as the cause fetal hypoxia :

1. Alteration in the basement membrane of chorionic villi 

decreasing oxygen transfer
2. Decreased uterine blood flow due to diabetic vasculopathy
and poor glicemic control
3. Metabolic changes
4. Hyperinsulinemia  increase fetal oxygen consumption and
decrease in arterial oxygen levels
 Management
• Diet and Exercise
• Metformin or Sulfonilurea (Category B)
• All other oral hypoglycemic agents should be discontinued
before pregnancy and insulin substituted
• Gold standard for pharmacological hypoglycemic therapy
in pregnancy is insulin.
 PRECONCEPTION COUNSELING

• All women of childbearing age with diabetes should be

counseled about the importance of near-normal glycemic
control prior to conception.
• Observational studies show an increased risk of diabetic
embryopathy, especially anencephaly, microcephaly,
congenital heart disease, and caudal regression directly
proportional to elevations in A1C during the first 10 weeks of
pregnancy.
The targets recommended by the Fifth International Workshop-
Conference on Gestational Diabetes Mellitus:
• Fasting ≤ 95 mg/dL (5.3 mmol/L) and either
• One-hour postprandial ≤140 mg/dL (7.8 mmol/L) or
• Two-hour postprandial ≤120 mg/dL (6.7 mmol/L)
 Nutritional Therapy
• Avoid single, large meals containing foods with a high percentage of
simple carbohydrates that release glucose rapidly from the
maternal gut (complex carbohydrates and fiber)
• Obese women (BMI > 30 kg/m2), a 30% to 33% calorie restriction
(to 25 kcal/kg of actual weight per day or less).
• Moderate restriction of dietary carbohydrates to 35% to 40% of
calories has been shown to decrease maternal glucose levels and
improve maternal and fetal outcomes
 • Reduce hepatic glucose production
• Decreases intestinal absorption of glucose
• Improves insulin sensitivity by increasing peripheral glucose uptake and utilization

Diabetes Spectrum Volume 27, Number 4, 2014

 When to start insulin

• Symptomatic hyperglycemia, fasting plasma glucose >6.9

mmol/L (125 mg/dL), or random plasma glucose >11.1
mmol/L (200 mg/dL).
• Blood glucose targets are not maintained 1 to 2 weeks after
introducing changes to diet and initiating exercise.
• Fetal macrosomia is suspected by ultrasound investigations.
 Dosage

0.8 units/kg/day in the first trimester, 1.0 unit/kg/day in the

second trimester, and 1.2 units/kg/day in the third trimester
 Type of Insulin

• Analogue insulin (Rapid acting): aspart, lispro (start 5-15’,

active 3-4 h)
• Human insulin Regular (short acting): Humulin S, Actrapid,
Insuman Rapid (start 30’, active 5-8 h)
• NPH (intermediate acting): Humulin I, Insuman basal,
Insulatard (start 1-3 h, active 16-24 h)
• Long acting: Ultralente (start 4-6 h, active 32 h)
• Premixed: NPH and reguler (start 30’, active 16-24 h),
ultralente and semilente
Insulin types

Onset is when the insulin usually

starts to work. The start of the
curve (left side) shows this.

Peak is when the insulin usually

has its strongest effect. The highest
part of the curve shows this.

Duration is how long the insulin

usually works. The end of the curve
(right side) shows this.
 Mean glucose levels were significantly higher in the twin
pregnancy and IGT groups at 24 and 48 h after the
administration of dexamethason than those in the singleton
pregnancy group (P < 0.05)
 MD 95% CI
Fasting blood glucose −18.13 mg/dl –33.85, –2.41
2-h post-prandial blood sugar −34.87 mg/dl –75.44; 5.69
HbA1C -0.54 -0.86, -0.21
Total cholesterol −32.37 mg/dl –57.39,–7.35
LDL −11.19 mg/dl –21.14,–1.25
HDL 7.43 mg/dl -0.36, 15.21
Triglycerides -13.17 mg/dl 40.00, 13.65
• 27.5% of normal pregnant women and 85% of women with GDM
had vitamin D deficiency, with serum 25(OH)D levels <20 ng/mL.
Serum levels of 25(OH)D were lower in women with
• GDM than normal pregnant women (P < .01)

Am J Obstet Gynecol 2013;209:560.e1-8.

 Postpartum Follow-up

• The OGTT is recommended over A1C at the 6- to 12-week

postpartum visit because A1C may be persistently impacted
(lowered) by the increased red blood cell turnover related to
pregnancy or blood loss at delivery.
• Women should also be tested every 1–3 years thereafter if 6-
to 12-week 75-g OGTT is normal
 Gestational Diabetes Mellitus and
Type 2 Diabetes

• Increased risk of conversion to type 2 diabetes over time and

not solely within the 6- to 12-week postpartum time frame
• Significantly lower in women who followed healthy eating
patterns
• Both metformin and intensive lifestyle intervention prevent or
delay progression to diabetes

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

 Contraception

Women with diabetes have the same contraception options and

recommendations as those without diabetes.

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

 Recommendations
• Test for undiagnosed type 2 diabetes at the first prenatal visit
in those with risk factors, using standard diagnostic criteria. B
• Test for gestational diabetes mellitus at 24–28 weeks of
gestation in pregnant women not previously known to have
diabetes. A
• Screen women with gestational diabetes mellitus for
persistent diabetes at 6–12 weeks postpartum, using the oral
glucose tolerance test and clinically appropriate non-
pregnancy diagnostic criteria. E

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

 Recommendations
• Women with a history of gestational diabetes mellitus should
have lifelong screening for the development of diabetes or
prediabetes at least every 3 years. B
• Women with a history of gestational diabetes mellitus found
to have prediabetes should receive lifestyle interventions or
metformin to prevent diabetes. A

Diabetes Care 2016;39(Suppl. 1):S13–S22 | DOI: 10.2337/dc16-S005

Thank you