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Diabetes in Pregnancy
Dr Thomas Paul MD DM (Endo)
Dr. Mathew John MD DM(Endo)
Department of Endocrinology
Christian Medical College
Vellore
Pregnancy may be complicated by diabetes
in two distinct forms:
Gestational diabetes mellitus (GDM) is defined as glucose
intolerance of varying severity with onset or first recognition
during pregnancy. This subset constitutes 90% of women with
pregnancies complicated by diabetes. The most important
perinatal concern in this group is macrosomia with resulting
birth trauma. More than 50% women ultimately develop
diabetes in the ensuing 20 years and this is linked with obesity.
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Pre-gestational diabetes is diabetes that antedates
pregnancy. Pregnancies which are complicated by pregestational diabetes, type-1 or type-2, carry an additional risk to
both mother and fetus beyond the effects on fetal growth and
development in mid and late pregnancy.
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Classification
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Pregestational diabetes: A lady with known diabetes who
conceives while on treatment with diet, oral hypoglycemic
agents or insulin.
Type 1 DM, Type 2 DM, Secondary DM
Gestational diabetes mellitus is defined as glucose
intolerance of variable degree with onset or first recognition
during pregnancy. Some patients with fasting
hyperglycemia detected early in pregnancy may be missed
cases of diabetes that predated pregnancy. Women found
early in pregnancy to have gestational diabetes are a highrisk subgroup.
Magnitude of problem: GDM
 GDM varies worldwide and among different racial and ethnic groups
within a country.
 Variability is partly because of the different criteria and screening
regimens
 Prevalence :
India: 0.56% -6% (Ramachandran A et al 1994; Hill et al., 2005)
USA: increased from 2.1–4.1% in the period 1994 to 2002 with
significant increases in all racial/ethnic groups (Dabelea et al., 2005).
Native Americans, Asians, Hispanics, African-American, Aboriginal
women are at higher risk (Ferrara, 2007).
Ramachandran A, Snehalatha C, Shymala P, Vijay V, Viswanathan M. Prevalence of diabetes in pregnant women--a
study from southern India. Diabetes Res Clin Pract. 1994;25:71-74.
Hill JC, Krisgnaveni GV, Annamma I, Leary SD, Fall CH. Glucose tolerance in pregnancy in South India:
relationships to neonatal anthropometry. Acta Obstet Gynecol Scand. 2005;84:159-65
Dabelea, D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ, Hamman RF, McDuffie RS. Increasing Prevalence of
Gestational Diabetes Mellitus (GDM) Over Time and by Birth Cohort. Diabetes Care 2005;28:579-584
Ferrara A: Increasing prevalence of gestational diabetes mellitus. Diabetes Care 2007;30:S141-S146
Risk Factors for gestational diabetes screening
1. Strong family history of diabetes
2. Women who have given birth to large infants (>4 kg; 8 lbs
13 oz)
3. History of recurrent fetal loss
4. Persistent glycosuria
5. Age > 25 years
6. Past history of glucose intolerance or diabetes in a previous
pregnancy
Risk Factors for gestational diabetes screening
7. Obesity; overweight women (>15% of non-pregnant ideal body
weight)
8. Ethnic group with a high prevalence of diabetes (e.g. Pima
Indians, Asians, Hispanic)
9. History of stillbirth, unexplained neonatal death, congenital
malformations, prematurity.
10. History of pre-eclampsia or polyhydraminos
11. Chronic hypertension
12. Recurrent severe moniliasis or urinary tract infection
13. History of traumatic delivery with an associated neurological
disorder in the infant
Whom to screen?
Risk stratification
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Low risk: no screening
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Average risk: at 24-28 weeks
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High risk: as soon as possible
Screening is ideally initiated between the 24th and 28th weeks
of pregnancy or earlier if any of the risk factors are present.
Low risk for GDM
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Age <25 years
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Weight normal before pregnancy
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Member of an ethnic group with a low prevalence of
GDM
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No known diabetes in first-degree relatives
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No history of abnormal glucose tolerance
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No history of poor obstetric outcome
Intermediate risk for GDM
Must exhibit one risk factor from the list in slide 5.
High risk for GDM
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Marked obesity
Prior GDM
Glycosuria
Strong family history
Ethnic group with high diabetes prevalence
All Indian women and women of Indian origin should
be screened for gestational diabetes mellitus
as they belong to a high risk ethnicity
Screening test
 Glucose Challenge Test (GCT): An excellent screening test for
gestational diabetes is the measurement of plasma glucose 1 hour
after ingesting 50 g of glucose.
A plasma glucose level obtained one hour after a 50 g glucose
load administered at any time of the day without regard to the time
since the last meal, has become a well validated and widely
applied screening procedure for women between 24 and 28
weeks of gestation.
Using a cut-off value > 140 mg/dl identifies 80% women with GDM
Using a cut-off value > 130 mg/dl identifies 90% women with GDM
Women with elevated GCT values require a diagnostic oral
glucose tolerance test
Screening test
Oral Glucose Tolerance Test (OGTT): Measurement of plasma
glucose after ingesting 100 g of glucose.
Timing of
measurement
Fasting
National Diabetes
Data Group (1979)
105 mg/dl
Carpenter and
Coustan (CC) 1982
95 mg/dl
1 hour
190 mg/dl
180 mg/dl
2 hour
165 mg/dl
155 mg/dl
3 hour
145 mg/dl
140 mg/dl
> 2 values must be abnormal; for at least 3 days prior to the test, the patient should have an
unrestricted diet and unlimited physical activity. The patient should fast for 8 hours before the
test. The CC criteria detects 54% more women with GDM than the NDDG criteria
Classification: and diagnosis of diabetes mellitus and other categories of glucose intolerance: National
Diabetes Data Group. Diabetes 1979;28:1039–1057
Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol.
1982;144:768-73.
Urine monitoring
Urine glucose monitoring is not useful in gestational diabetes
mellitus
Urine ketone monitoring may be useful in detecting insufficient
caloric or carbohydrate intake in women treated with calorie
restriction
Effects of GDM on the fetus
Congenital abnormalities
 Neonatal hypoglycemia
 Macrosmia (big baby syndrome > 4 Kg or >8 lb 13 oz)
 Jaundice
 Polycythemia / hyperviscosity syndrome
 Hypocalcemia, hypomagnesemia
 Birth trauma (due to macrosmia and shoulder dystocia)
 Prematurity
 Hyaline membrane disease
 Apnea and bradycardia
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The risk of fetal anomalies is not increased in GDM patients. However, the
risks of unexplained still births (during the last 4-8 weeks of gestation) are
similar to pre-gestational diabetes.
Effects of GDM on neonates
Respiratory distress
Hypoglycemia
Hypocalcemia
Hyperbilirubinemia
Cardiac Hypertrophy
Long term effects on cognitive development
Macrosomic infant
Macrosomia (large for gestational age or big baby syndrome)
(birth weight >90% percentile for gestational age)
Macrosomia is a result of persistent maternal hyperglycemia
leading to fetal hyperglycemia and prolonged fetal
hyperinsulinism. This stimulates excessive somatic growth
mediated by insulin-like growth factors (IGFs). Macrosomia
affects all organs except the brain.
Congenital abnormalities due to GDM
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Cardiac (most common): transposition of great vessels,
Ventricular septal defect, Atrial septal defect
Central nervous system (7.2%): spina bifida, Anencephaly,
hydrocephalus
Skeletal: cleft lip/palate, caudal regression syndrome
Genitourinary tract: ureteric duplication
Gastrointestinal: anorectal atresia
Renal agenesis, Duplex ureters, Cystic Kidney
Situs inversus
Poor glycemic control at time of conception: risk factor
Caudal regression syndrome
(abnormal development of lower spine)
Caudal regression syndrome
Effects of GDM on the mother
 Pre-eclampsia: affects 10-25% of all pregnant women with
GDM
 Infections: high incidence of chorioamnionitis and postpartum
endometritis
 Postpartum bleeding: high incidence caused by exaggerated
uterine distension
 Cesarian section more common due to fetal macrosmia and
cephalo-pelvic disproportion
 Weight gain
 Hypertension
 Miscarriages
Third trimester fetal deaths
 Long term risk of type-2 diabetes mellitus
Effect of pregnancy on diabetes
 More insulin is necessary to achieve metabolic control
Progression of retinopathy: esp. severe proliferative retinopathy
Progression of nephropathy: especially if renal failure +
 Increased risk of Coronary artery disease, and a high risk of
maternal death in post MI patients
 Cardiomyopathy
Patient education
Cornerstone in GDM management
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Instruct mother about maternal and fetal complications
Medical Nutrition therapy
Glycemic monitoring: teach mother about self monitored
blood glucose measurement and glycemic targets
Pre-conception counseling
Fetal monitoring: ultrasound
Planning on delivery
Long term risks
Glycemic control targets
 Tight glycemic control can reduce fetal risk. But, stringent glycemic
control puts the mother at increased risk of hypoglycemic events and the
fetus at risk of being small-for-gestational age.
 American Diabetes Association Recommendations:
Fasting whole blood glucose
<95 mg/dl
1 hr postprandial blood glucose
<140 mg/dl
2 hr postprandial blood glucose
<120 mg/dl
These are venous plasma targets, not glucometer targets
Why these tight glycemic targets?
Prospective study in type-1 patients with pregnancy
Fasting blood sugar
Macrosomia
>105 mg/dl
95-105
<95 mg/dl
28.6 %
10%
3%
Self monitored blood glucose (SBMG)
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4 times/day minimum, fasting and 1 to 2 hours after start of
meals
Maintain log book
Use a memory meter
Calibrate the glucometer frequently
Medical Nutrition and Exercise therapy
 provide
necessary nutrients for mother and fetus to ensure adequate
gestational weight gain
 control glucose levels
 prevent starvation ketosis
 aerobic exercise, exercise that does not stress the trunk
Current weight in relation to
ideal body weight
Daily caloric intake
(kcal/kg)
Recommended pregnancy
weight gain (kg)
<80-90%
36-40
28-40
80-120% (ideal)
30
25-35
120-150%
24
15-25
>150%
12-18
15-25
Medical nutrition therapy
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Approximately 30 kcal/kg of ideal body weight
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> 40-45% should be carbohydrates
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6-7 meals daily (3 meals, 3-4 snacks). Bed time snack to prevent ketosis
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Calories guided by fetal well being/maternal weight gain/blood sugars/
ketones
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Energy requirements during the first 6 months of lactation require an
additional 200 calories above the pregnancy meal plan
Insulin in GDM
Insulin used if fasting blood glucose >105 mg/dl or 1 hr
postprandial blood glucose >120 mg / dl on a diet
 Use basal bolus regime or pre-mixed insulin
 Short acting insulins (e.g. Lispro and Aspart) can be used to
achieve postprandial control
 Long acting insulins (Glargine and Determir) are NOT licensed
in pregnancy
 Insulin requirements increase by 50% from 20-24 weeks to
30-32 weeks, after which insulin needs often stabilize.
Oral Hypoglycemic agents
Glyburide is a clinically effective alternative to insulin in GDM
(Langer et al. 2000)
Metformin may be effective in GDM (Ratner et al., 2008;
Coustan, 2007)
Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women
with gestational diabetes mellitus. N Engl J Med. 2000;343:1134-8
Ratner RE, Christophl CA, Metzger BE, Dabalea D, Bennett PH, Pi-Sunyer X, Fowler S, Kahn SE, Diabetes
Prevention Program Research Group. Prevention of diabetes in women with a history of gestational diabetes:
effects of metformin and lifestyle interventions. J Clin Endocrinol Metab. 2008;93:4774-9
Coustan DR Pharmacological management of gestational diabetes: an overview. Diabetes Care. 2007;30 Suppl
2:S206-8.
Preconception counseling
All women with pre-existing type-1 or type-2 diabetes, when planning on
pregnancy, should receive pre-conception counseling so that they
understand the importance of achieving near-normal blood glucose before
conception to reduce the risk of congenital malformations and spontaneous
abortions.
Assess maternal and fetal risk
 Mother should learn self-administration of insulin and regular monitoring of
blood glucose.
 Target: HbA1c < 7%
 Emphasize diet and exercise
 Folic acid supplementation: 5 mg/day
 Ensure no transmissible diseases: HBsAg, HIV, rubella
 Try and achieve normal body weight: diet/exercise
 Stop drugs: oral hypoglycemic drugs, ACE inhibitors, beta blockers and
potentially teratogenic drugs
Clinical parameters checked at each visit
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Medications
Pre-pregnancy weight
Weight gain
Edema
Pallor
Thyroid enlargement
Blood pressure
Fundal height
Laboratory parameters to be
monitored at each visit
 Hemoglobin
 Blood Sugar
 HbA1C (first trimester only)
 Urine microscopy and albumin
 Thyroid function (if goiter present)
Fetal monitoring
 Baseline ultrasound : fetal size
 Ultrasound evaluation of neural tube defects and other
congenital malformations should begin by 15-21 weeks of
 At 18-22 weeks: fetal anatomic survey, major malformations
 At 20-22 weeks: fetal echocardiogram for cardiac defects
 At 26 weeks onwards: ultrasound to evaluate fetal growth and
amniotic fluid volume
 Third trimester: Fetal surveillance to reduce risk of still birth:
include non-stress test, biophysical profile, maternal monitoring
of fetal activity, frequent USG for accelerated growth
 abdominal: head circumference
Timing of delivery
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Small risk of late intra-uterine death even with good
glycemic control
Delivery usually at 38 weeks
Beyond 38 weeks, increased risk of intrauterine death
without an increase in RDS
Management of labor and delivery
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Vaginal delivery: preferred
Cesarian section only for routine obstetric indication
GDM alone is not an indication !
> 4.5 Kg fetus: Cesarean delivery may reduce the likelihood
of brachial plexus injury in the infant
Unfavorable condition of the cervix is a problem
Maintain euglycemia during labor
Maternal hyperglycemia in labor: fetal hyperinsulinemia and
worsen fetal acidosis
Maintain sugars: 80-120 mg/dl (capillary: 70-110mg/dl )
Feed patient the routine GDM diet
Maintain basal glucose requirements
Monitor sugars 1-4 hrly intervals during labour
Give insulin only if blood sugar >120 mg/dl
Glycemic management during labour
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Later stages of labour: start dextrose to maintain basal
nutritional requirements: 150-200 ml/hr of 5% dextrose
Elective Cesarian section: check fasting blood sugar; if
within target range no insulin is needed; start dextrose drip
Continue hourly self monitored blood glucose
Post delivery keep patients on dextrose-normal saline till fed
No insulin unless sugars more than normal ( not GDM
targets ! )
Post partum follow up
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Check blood sugars before discharge
Breast feeding: helps in weight loss
Lifestyle modification: exercise, weight reduction
Oral glucose tolerance test at 6-12 weeks
postpartum: classify patients into normal/impaired
glucose tolerance and diabetes
Preconception counseling for next pregnancy
Increased risk of cardiovascular disease,
future diabetes and dyslipidemia
Immediate management of neonate
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Hypoglycemia: 50 % of macrosomic infants
5–15 % optimally controlled GDM
Starts when the cord is clamped
Exaggerated insulin release secondary to pancreatic ß-cell
hyperplasia
Increased risk: blood glucose during labor and delivery
exceeds 90 mg/dl
Anticipate and treat hypoglycemia in the infant
Management of neonate
 Hypoglycemia <40 mg/dl
 Encourage early breast feeding
 If symptomatic give a bolus of 2- 4 ml/kg, IV, 10% dextrose
 Check after 30 minutes, start feeding
 IV dextrose : 6-8 mg/kg/min infusion
 Check for calcium, if seizure/irritability/RDS
 Examine infant for other congenital abnormalities
Long term risk: offspring
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Increased risk of obesity and abnormal glucose
tolerance due to changes in fetal islet cell function
Encourage breast feeding: less chance of obesity in
later life
Lifestyle modification
Conclusion
 Gestational diabetes is a common problem in worldwide
 Risk stratification and screening is essential in all pregnant
women, particularly those from ethnicities with increased risk
 Tight glycemic targets are required for optimal maternal and
fetal outcome
 Patient education is essential to meet targets
 Long term follow up of the mother and baby is essential
17 pound baby born to Brazilian diabetic mother Courtesy: MSNBC News Services
Jan. 24, 2005