Diabetes Mellitus

Complicating Pregnancy

BIRHANE TEKLAY(M.D)
GYN/OBS DEP’T
 Outline of the Lecture
• Introduction
• Incidence
• CHO metabolism during pregnancy
• Classification
• Diagnosis
• Pre-pregnancy counseling
• Treatment of diabetes in pregnancy
• Post partum consequences

10/26/20
 Introduction
• Reproduction in diabetic women was not existent
(death, infertility)
• Occasionally when pregnancy occurred
- High perinatal mortality 60%
- High maternal mortality 20%
• In the 1920s, discovery of insulin

10/26/20
• The No 1 medical disorder complicating
pregnancies
• Prevalence rising
• Type 2 - Diabesity

10/26/20
 Incidence
– 2-3% of pregnancies are complicated by DM
– 90% of cases represent women with GDM
– Gestational Diabetes Mellitus
• Any degree of glucose intolerance with Onset or
first recognition during pregnancy
– Pre insulin era – Pregnancy in diabetic women was
uncommon and was likely to be accompanied by fetal
mortality and risk for maternal death as well.

– Infertility : Amenorrhea in 50%

10/26/20
 CHO metabolism in normal pregnancy

Early pregnancy
– Increased sensitivity to insulin
– Increased secretion of insulin
– Lipogenesis is favored – fat storage
– Less calorie in take – nausea, vomiting
– Frequent hypoglycemic reaction
– ↑ Glycogen Deposition in Peripheral tissue
– ↓Hepatic glucose production
– ↓ Gluconeogenesis from amino acids

10/26/20
Diabetic mothers require less insulin
 CHO metabolism in normal pregnancy
Late Pregnancy
– Diabetogenic
• Sharp increase in HPL
• Increased insulin resistance
– Accelerated starvation
• Save glucose for the fetus  lipolysis
– Postprandial hyperglycemia (delayed emptying)
– women with overt diabetes cannot respond to this
stress and require additional insulin therapy
Diabetic mothers require additional insulin than in
early pregnancy

10/26/20
 Classification
 Predicts pregnancy outcome and prognosis
• Classification:
 Onset of the disease
 Duration of the disease
 Vascular complications
 Insulin requirement

10/26/20
10/26/20
 Classification Cont…
• ACOG(1994) classification:
– White and modified white failed to recognize
metabolic instability
– Pregnancy outcome depends not only on duration
and vascular complication but also on metabolic
instability:
- Several episodes of DKA
- Wide variations in blood sugar
- Frequent hypoglycemic reaction
- Non compliance
- Frequent hospital admissions

10/26/20
 Classification Cont…
1994 ACOG Classification:
1. Gestational diabetes
a) Low risk
b) High risk: macrosomia, polyhydramnios, preeclampsia
2. Insulin dependent without end organ damage (B
and C of White)
a) Stable
b) Unstable
3. Insulin dependent with end organ damage (D, F, R,
T, and H )

10/26/20
 Gestational Diabetes Mellitus
• GDM is any degree of impaired glucose
tolerance of with onset or first recognition
during pregnancy.
• Fasting hyperglycemia early in pregnancy
almost invariably represents overt diabetes.

10/26/20
 Risk factors for GDM
• Family Hx of DM, especially in first degree
relatives
• Prepregnancy body mass index over 30 kg/m2
• Age greater than 25 years
• Previous delivery of macrosomic baby
• Personal Hx of abnormal glucose tolerance
• Previous unexplained perinatal loss or birth of a
malformed child
10/26/20
• Maternal birthweight greater than 4 kg / less
than 2.7kg
• Glycosuria at the first prenatal visit
• Polycystic ovary syndrome
• Current use of glucocorticoids
• Essential hypertension or pregnancy-related
hypertension

10/26/20
 DIAGNOSIS
Screening for GDM:
– Despite 3 decades of research – no consensus
– Controversial issues:
1. Universal/Selective screening
- 0.1% - 35% of GDM will be missed

10/26/20
 WHY screening?
• Several adverse outcomes are associated with
increasing levels of glucose impairment:
– Preeclampsia
– Polyhydramnios
– Fetal macrosomia
– Birth trauma
– Operative delivery
– Perinatal mortality
– Neonatal metabolic complications (hypoglycemia,
hyperbilirubinemia, hypocalcemia, polycythemia)

10/26/20
 Whom to screen?
• Universal Vs Selective
– ADA – selective (high risk women)
– ACOG - Universal (all pregnant women)
– Our setup

10/26/20
• 5th international workshop-conference on
GDM recommendations for selective
screening
• Low Risk  
• Blood glucose testing not routinely required if all of
the following characteristics are present:    
– Member of an ethnic group with a low prevalence of
gestational diabetes    
– No known diabetes in first-degree relatives    
– Age less than 25 years

10/26/20
 – Weight normal before pregnancy

– Weight normal atbirth  

  
– No history of abnormal glucose metabolism    

– No history of poor obstetrical outcome

10/26/20
• High risk
• Perform blood glucose testing as soon as feasible if
one or more of these are present
– Severe obesity
– Strong family history of type 2 DM
– Previous history of DM
• If GDM is not diagnosed repeat at 24-28wks of
gestation

10/26/20
• Average risk
• Perform blood glucose testing at 24-28 wks
using either
• Two step procedure: 50g oral GCT followed by
100g OGTT
• One step procedure: 100g OGTT

10/26/20
 When to screen?
• Screening is performed at 24 to 28 weeks of
gestation.
• But it should be done at the first ANC visit if
there is a high degree of suspicion that the
pregnant woman has undiagnosed type 2 DM:
– marked obesity,
– personal history of GDM,
– Glycosuria, or
– Strong family history of diabetes
10/26/20
 How to screen?
• Plasma glucose level is measured 1 hour after
a 50-g glucose load without regard to the time
of day or time of last meal.
– If the Value is >140 mg/dL  diagnostic test for
GDM.

10/26/20
 DIAGNOSTIC TESTING

• For Women who screen positive (PGL > 140mg/dl

after screening dose of 50 gm Glucose).
• Three-hour 100-g OGTT (oral glucose tolerance test)
– Patients are going to fast for 8 hours before the
test
– Plasma glucose level is to be measured:
• Before ingestion of the 100 gm glucose
• 1 hour after ingestion
• 2 hours after ingestion
10/26/20
• 3 hours after ingestion
10/26/20
• Interpretation of OGTT:
– Positive if two or more of the values are more than
the cut off values. => GDM diagnosed

10/26/20
 Pregestational (Overt) Diabetes
• Has a significant impact on pregnancy outcome.
• The fetus, and the mother can have
complications directly attributable to diabetes.
• Successful outcomes with overt diabetes is
related to the degree of glycemic control, and to
the degree of any underlying cardiovascular or
renal disease.

10/26/20
 Pre-pregnancy counseling
• Not later than 3 months before pregnancy

– Strict glycemic control 6%  2% (general

population)
– HbA1C should be < 7% at conception
– Folic acid 400 g or 4000 g
– Vitamin C: free radical oxygen species

10/26/20
 Effect of pregnancy on Diabetes
• Insulin resistance
– HPL (Human Placental lactogen )
– production of cortisol, estriol and progesterone
– destruction of insulin by kidney and placenta
– lipolysis use of fat by fetus

10/26/20
 Effect of pregnancy on Diabetes

• HPL - Lipolysis
- release of fatty acid and glycerol
-↓Utilization of glucose and amino acids
• In normal pregnancy 44% decline in insulin
sensitivity compared to 56% in pregnancy
complicated by GDM
• → progressive retinopathy
• → Worsening nephropathy
• → Difficulty in metabolic control
↑insulin requirement
10/26/20 ↓ insulin requirement after delivery at a rapid rate
 Effect of pregnancy on Diabetes

Diabetic retinopathy
- Worsened by pregnancy
- 10% of those without retinopathy  benign
retinopathy
- 6% with benign retinopathy  proliferative
retinopathy

10/26/20
 Effect of pregnancy on Diabetes
Diabetic nephropathy
- 5-10% pregnant women
- Increased chance of preeclampsia
. 17% in diabetics with nephropathy
. 8% in diabetics with out nephropathy
- >2g proteinuria 24hrs and creatinine > 1.5mg/dl

 relative contraindication
10/26/20
 Effect of pregnancy on Diabetes
Cardiovascular disease
- MMR > 50% in some series
- The decision for conception, serious
consideration

10/26/20
 Effect of pregnancy on Diabetes
Hypertension
– Stop antihypertensive drugs for the 1st 8 weeks
– After 8 weeks: methyldopa, hydralazine, Ca
blocker and  blocker are safe
– ACE-I should be discontinued

10/26/20
 Effect of DM on pregnancy
• Maternal
– preeclampsia
– ↑ infections -UTI
-Chorioamnionitis
-Endomyometritis
-moniliasis
– PPH
– Polyhydraminos
– ↑ C/S rates

10/26/20
 Fetal effects
Perinatal death:
– Sudden unexplained stillbirth occur in 10 - 30% in
the pregnancies complicated by GDM
– Common after 36 weeks in patients with:
• vascular disease,
• poor glycemic control,
• polyhydramnios,
• macrosomia or
• preeclampsia
– Cause - chronic intrauterine hypoxia
10/26/20
 Fetal effects
Macrosomia
– Birth weight in excess of
4000gm
– Increased adiposity, muscle
mass and organomegaly
– Danger
• Shoulder dystocia
• Traumatic birth injury and
asphyxia
• ↑ Operative delivery
• Obesity in later life
10/26/20
• Pederson hypothesis
– Maternal hyperglycemia Excess fetal
growth
Incidence 50% of pregnancies GDM

10/26/20
 Fetal effects
Congenital malformations
– 2 - 6 fold increase in major malformations
– Insult must act before 8th week
– Sacral agenesis occur with 200-400 times
more often than other women

10/26/20
 Fetal effects
Proposed mechanism
– Hyperglycemia
– Ketone body excess
– Somatomedin inhibition
– Arachidonic acid deficiency
– Free oxygen radical

10/26/20
 Fetal effects
Congenital malformations

• CVS -Transposition of great vessel, VSD, ASD

• CNS – Anencephaly, meningomyelocele,
microcephaly, encephlocele
• Skeletal – Caudal regression syndrome , spinabifida
• GIT – Tracheoesophagial fistula
• GUS – Absent kidney, Polycystic kidney

10/26/20
 Fetal effects
Hypoglycemia - during the first 24 hours of life,
common in macrosomic infants up to 50%
Respiratory distress syndrome - Mechanism
unknown
Hypocalcaemia and hypo magnesium
Hyperbilirubinemia and polycythemia

10/26/20
 Treatment of diabetes in pregnancy
Components of the treatment:
– Monitoring of blood glucose
– Diet
– Exercise
– Administration of insulin
– Obstetric surveillance
– Treatment during labor and delivery

10/26/20
 Treatment
• Glucose monitoring
- GDM - At least four times a day
- Fasting
- 2hr postprandial

10/26/20
 Treatment
• Postprandial monitoring has the following
benefits:
. Better glycemic control (HbA1C mean 6.5%)
. Lower rate of CS for CPD (12% Vs 36%)
– Target : Fasting < 105mg /dl
- 2hr ppr < 120 mg /dl
- 1hr ppr < 140mg /dl

10/26/20
 Treatment Cont…
• Pregestational - At least 5 – 7 x /day
– Pre- and post-prandial measurements plus
middle of the night & bed time
– Urine ketones
• Target
– Before break fast 60-90mg/dl
– Before lunch, super & bed time 60-105mg/dl
– 2hr after meal < 120 mg/dl
– 1hr after meal < 140 mg/dl
– HbA1C < 6%

10/26/20
 Treatment Cont…
• Diet
– Rx in GDM for fasting < 105 mg/dl and 2hr ppr
< 120 mg/dl
– Composition
• 50-60% CH2O
• 20% protein
• 25-30% fat with <10% saturated fat

10/26/20
• Carbohydrate content
• Carbohydrate is restricted to 33 to 40% of calories,
• protein about 20 % and
• fat about 40% .
• With this calorie distribution, 75 to 80% of women with
GDM will achieve normoglycemia.
• Calorie distribution
• Breakfast —small - 10% of total calories
• Lunch — 30 percent of total calories
• Dinner — 30 percent of total calories
• Snacks — approximately 30 percent of total calories
• Three meals and three snacks are suggested
 Treatment Cont…
• Exercise
– Increase insulin sensitivity (GDM, type II)
– In type I the need is not clear  hypoglycemia
– Aerobic exercise 3x / Q wk for 20 min
– Exercises that cause little stress on trunk
• Walking
• Upper arm exercise
• The effect of exercise is seen after 4 -6 wk

10/26/20
 Treatment Cont…
• Insulin

• ACOG recommends the administration of insulin to

reduce the risk of macrosomia when:
– Fasting glucose concentration ≥ 95 mg/dL or
– One hour postprandial glucose >130-140 mg/dL or
– Two hour-postprandial blood concentration ≥120 mg/dL

10/26/20
 – GDM
• 15-20%
• FBG >105 mg/dl
• 2hr pp > 120 mg/dl
• After 2 weeks of diet Rx
 int. acting insulin 5-10u at bed time
•  PP  add 10u regular insulin before the
meal

10/26/20
 Treatment Cont…
Pregestational DM
– 2-3 injections /day 30min - 1hr before meal
– 0.7units/kg - 17 weeks
– 0.8 units/kg - 18-26 weeks
– 0.9 units/kg - 27-36 weeks
– 1unit /kg - 37 up to delivery

10/26/20
 Treatment Cont…
– 1.5 - 2 unit / kg in the obese
– In type II the dose is higher
– insulin pump is other modality
• Superior to conventional therapy in
pregnancy

10/26/20
 Treatment Cont…
• Oral hypoglycemic agents
– Early studies show teratogenicity and poor
glycemic control
– Some centers are using (Glyburide)
• Inexpensive
• Better compliance
• No need of training
• No difference in glycemic control

10/26/20
 Obstetric management
• First trimester
• Date the pregnancy (LNMP and US)
• Renal fuction test, ophthalmic and cardiac evaluation
• HbA1C
• Weight and baseline tests
• Second trimester
• Check BP
• Careful FH measurement
• Maternal serum Αfp at 16-18wks
• US for detection of fetal anomaly
• Third trimester
• Assess BP values frequently
• Serial US to assess fetal growth and fetal surveillance
 Treatment Cont…
• Follow up for congenital malformations:
– HbA1C >7%  congenital malformation
– >10% significant
– Lab : MSAFP (16 weeks)
: NTD 2% in DM; 0.1 - 0.2 in general
population

10/26/20
 Treatment Cont…

– U/S : 8 - 10 weeks  anencephaly and

blighted ova
:18 to 20 weeks  major anomaly.
: 24-26 weeks  echo.
– No increased risk in GDM

10/26/20
 Treatment Cont…
• Macrosomia
– Defined as BW > 4 - 4.5 kg or > 90%ile for
GA
– 62.5% in diabetes
– U/S : starting 20 weeks Q4 weeks
: margin of error 25%

10/26/20
 Treatment Cont…
• Labor and delivery
– Timing of termination
• Stable and without vascular Cxn : EDD
• Unstable & with vascular Cxn : L/S ratio & PG
– Mode of delivery
• EFW > 4500 gram  C/S
• EFW 4000 - 4500 gram controversy
• Proliferative retinopathy  C/S

10/26/20
• Optimal time is 38-40wks, not later than 40
• Induction of labor is recommended @ 38wks
in patients with poor control and macrosomia
• If early delivery is indicated lung maturity
should be checked
• CS is done only for obstetric indications

10/26/20
 Treatment Cont…
• Intrapartum glycemic management
• Target to keep BGL 80-120
1. Insulin infusion method
• Withhold the morning dose
• Begin regular insulin infusion at 0.5u/hr
• Monitor maternal glucose hourly and adjust the drops
acc. to the result

10/26/20
 – During labor insulin requirement is low
– Allow evening meal, bedtime snack, and
evening insulin
– No regular morning insulin
– Continuous infusion of 50u/500ml of R/L or
N/S
– BG Q1hr for pregestational and Q 4hr for GDM

10/26/20
 Treatment Cont…
– Discontinue insulin infusion
• After delivery
• BG < 70 mg/ dl  5% D/W infusion
– No insulin 24 - 48hrs postpartum  0.6 units
/kg or 60% of prepregnancy dose.

10/26/20
2. Intermittent subcutaneous injection method
• Give ½ the usual insulin dose in AM
• Begin and continue glucose infusion (D5W)
at 100ml/hr
• Monitor maternal glucose hourly & and give
regular insulin as needed

10/26/20
 Post-partum evaluation
• GDM – no treatment required, if need be use
oral hypoglycemic agents
– Need follow up as they may progress to overt
diabetes
• Type 1 – 1/3 to ½ of antepartum daily dose
• Type 2 – pre-pregnancy dose can be restarted
 Postpartum consequences

• GDM recurs in subsequent pregnancy in 50%

• GDM cases develop overt diabetes (40-60%) in
5th decade
– Wt loss, exercise, dietary control, insulin
treatment

10/26/20
 Postpartum Cont…
• GDM before 24 weeks manifest as overt in 9-
44% after delivery
• So post partum evaluation
- at 6-12 weeks
- If normal Q 3 yrs
- By 75 g oral glucose
Normal IFG/IGT DM
Fasting < 110 mg/dl 110-125 mg/dl >126 mg/dl

2 hours <140 mg/dl 140-199 mg/dl >200 mg/dl

10/26/20
 Thank you!

10/26/20