Diabetes and Pregnancy

Kimberly W. Hickey MD
Menachem Miodovnik MD
Basics
Description
Type 1 DM:
o Absolute insulin deficiency due to pancreatic -cell destruction.

Type 2 DM:
o

GDM:
o

Insulin resistance and insulin deficiency

Insulin resistance and relative insulin deficiency associated with

pregnancy

A major cause of maternal and fetal morbidity and mortality

Epidemiology
Types 1, 2, and GDM, affect 14% of pregnancies:
10% of these have pregestational DM
90% with GDM:
o

3% of these have undiagnosed Type 2 DM

Type 1 DM affects 1 in 300 women.

Risk Factors
Risk factors:
o History of GDM
o

Obesity

Age >25

1st-degree relative with DM

Ethnic groups:

Hispanic, African, South or East Asian, Pacific Island, or

Native American

History of macrosomia, shoulder dystocia, or unexplained stillbirth

Risk factors are also suggested criteria for early screening for GDM.

Genetics
Complex interaction of genes identified for Type 1 and Type 2 DM:
o Up to 18 different regions on the human genome have been linked to
Type 1 DM.
o

These regions (IDDM1IDDM 18) are located on chromosomes 1,2, 5,

6, 10, 14, 15, and 18.

HLA Class II alleles have been identified in region IDDM 1 and are
present in up to 40% of patients with Type 1 DM.

40% of those with Type 2 DM have a parent with DM, suggesting a

strong genetic basis.

No single marker occurring only in those destined to develop DM has yet been
identified.

In utero environment (imprinting) may affect risk of DM as adult (Barker

hypothesis).

Pathophysiology
Pregestational DM:
o Type 1 DM:

Pancreatic -cell destruction

Majority of cases thought to be autoimmune

Type 2 DM:

Failure of insulin to maintain glycemic homeostasis

Insulin resistance with progressive insulin secretory defect

Postprandial hyperglycemia that progresses to persistent

hyperglycemic state

GDM:
o

Increasing insulin resistance associated with advancing GA and

placental hormones

Associated Conditions
Maternal complications of DM:
o Diabetic retinopathy

Diabetic nephropathy

Coronary artery disease

Chronic HTN

Diabetic neuropathy

Maternal hypoglycemia

Obesity

Complications associated with DM and pregnancy:

o

Diabetic embryopathy:

Decreased rate of fertility

Increased rate of spontaneous abortion

Increased rate of major and minor congenital malformations

Abnormal fetal growth:

Macrosomia

Fetal growth restriction

Hypertrophic cardiomyopathy

Neonatal metabolic disturbances:

Hypocalcemia

Hypomagnesemia

Hypoglycemia

Polycythemia

Hyperbilirubinemia

Neonatal respiratory decompensation:

Increased rate of respiratory distress syndrome with poor

glycemic control

Increased rate of transient tachypnea of the newborn

Obstetric complications associated with DM:

o

Gestational HTN

Preeclampsia

Preterm delivery

Polyhydramnios

Infectious morbidity

Uteroplacental insufficiency

Stillbirth

Acute worsening of diabetic retinopathy

Diagnosis
Signs and Symptoms
History
Pregestational DM:
Polyuria
Polydipsia

Unexplained weight loss

Ketoacidosis

Polyhydramnios in absence of fetal anomalies

Tests

Diagnostic criteria for pregestational DM:

o Symptoms of DM and random plasma glucose of 200 mg/dL
o

Fasting plasma glucose level of 126 mg/dL

2-hour plasma glucose 200 mg/dL during an OGTT:

Screening and diagnostic criteria for GDM:

o

Screening at 2428 weeks EGA (unless risk factors for early screening)

1-hour 50-mg OGTT

If plasma glucose 130 mg/dL, do 3-hour OGTT

Diagnosis with 3-hour 100-mg OGTT:

o

75 g anhydrous glucose dissolved in water

GDM diagnosed if 2 abnormal plasma glucose values:

Fasting 95 mg/dL

1 hour 180 mg/dL

2 hour 155 mg/dL

3 hour 140 mg/dL

Assessment of end-organ involvement for preventive care and health

maintenance in 1st trimester if pregestational DM:
o

Exam by ophthalmologist for retinopathy

EKG if 35 years old, obese, hypertension, renal disease,

hypercholesterolemia, or DM for >10 years

Stress test if EKG suggests CVD

24-hour urine for protein and creatinine with serum creatinine to assess
renal function and estimate GFR

Thyroid panel for autoimmune disease

Hemoglobin A1C to assess glycemic control prior to conception or at

the 1st visit

Glucose monitoring:

Use glucometer with memory to provide feedback on targets of

glycemic control

Self-monitored plasma glucose concentrations on waking (fasting),

before each meal, postprandial, and nighttime: 7 measurements a day.

Consider 3 a.m. plasma glucose if unexplained persistent fasting

hyperglycemia

Targets: Fasting 6090 mg/dL, pre-meal 8095 mg/dL, 1-hour

postprandial 140 mg/dL, or 2-hour postprandial 120 mg/dL

Hemoglobin A1C as close to normal (6%) as possible without

hypoglycemia

Imaging
US:
o

Serial sonograms for fetal growth

Fetal ECHO for cardiac malformations

Treatment
General Measures
Interdisciplinary team for management
Intensive glycemic control:
o

Dietary regulation:

Reduce carbohydrates to 4050% of total calories OR focus on

low glycemic index carbohydrates as 60% of total calories

Total calories based on prepregnancy BMI. BMI 20, 3538

kcal/kg; BMI 2025, 30 kcal/kg; BMI 26, 2025 kcal/kg.

Calories as 3 meals and up to 4 snacks, adjusting for lifestyle

and work schedule

Control of chronic HTN

Photocoagulation for proliferative retinopathy, prior to pregnancy

Recommended exercise: 20 minutes a day, 34 times a week

P.445
Pregnancy-Specific Issues
Preconception measures:
o Intensive glucose control, as majority of birth defects occur before
pregnancy is recognized

Renal disease:

Pregnancy is not a risk factor for development or progression of

nephropathy.

Proteinuria may increase due to physiologic changes of pregnancy.

Progression of retinopathy associated with rapid normalization of glucose

levels, transient.

By Trimester
Routine prenatal labs PLUS:
Each trimester:

Hgb A1C to assess glycemic control

Evaluation of renal function

1st trimester:
o

US for accurate dating

Evaluation for CVD

Exam by ophthalmologist for retinopathy

2nd trimester:
o

Sonogram to screen for fetal anomalies

If pregestational DM, fetal ECHO 1820 weeks EGA

Sonograms for fetal growth every 4 weeks

3rd trimester:
o

Sonograms for fetal growth every 4 weeks

Antepartum fetal testing with NST and AFI or BPP twice weekly
starting at 32 weeks EGA or 28 weeks EGA if other obstetric
complications

Intrapartum:
o

Usual evening dose of insulin injection or insulin pump overnight until

arrival

Hold the morning dose of insulin.

Assess initial glucose concentration; then q1h in labor

Goal of plasma glucose concentrations between 70 and 100 mg/dL

throughout labor

Continuous insulin drips during labor:

Consult MFM or endocrinology for protocol

Postpartum:
o

Pregestational doses of insulin or pump rates

Risks for Mother

Diabetic ketoacidosis at much lower glucose levels (i.e., 250 mg/dL)
Proliferative retinopathy associated with rapid normalization of glucose levels

Increased frequency of hypoglycemic episodes, frequently asymptomatic

Increased risk for preeclampsia and gestational HTN

PTL

Increased risk of infection including pyelonephritis, endometritis, and

postpartum wound infections

Risks for Fetus

Risks associated with poor glycemic control:
o Fetal growth restriction or macrosomia with difficulty maintaining
euglycemia in the immediate postpartum period
o

Major congenital anomalies:

Higher hemoglobin A1C associated with higher rates of

congenital anomalies: NTDs, cardiac malformations

Caudal regression syndrome highly associated with poor

glycemic control.

Macrosomia with increased risk of shoulder dystocia and fetal injury:

Brachial nerve palsies, hypoxic neurologic insults, and death

Hypertrophic cardiomyopathy, with thickened ventricular septum and

walls

Neonatal hypocalcemia and/or hypomagnesemia

Neonatal hypoglycemia

Neonatal polycythemia with risks related to hyperviscosity

Hyperbilirubinemia

Stillbirth

Medication (Drugs)
Pregestational diabetes should be treated with an insulin regimen as first-line
therapy:
o Type I DM: 0.9 U/kg/d in 1st trimester; 1 U/kg/d in 2nd trimester; and
1.2 U/kg/d in 3rd trimester
o

Type II DM: 0.9 U/kg/d in 1st trimester; 1.2 U/kg/d in 2nd trimester;
1.6 U/kg/d in 3rd trimester

If GDM doesn't respond to exercise and diet, begin with oral hypoglycemic
agents (glyburide):
o

If glycemic control not adequate with glyburide initiate insulin therapy:

o

Biphasic insulin requirements: Increasing dose up to 30 weeks then

stabilizing. Estimate dose based on BMI. BMI 25, 0.8 U/kg/d; BMI
25, 1 U/kg/d.

Insulin dosing:
o

Glyburide (sulfonylurea): Starting dose 2.5 mg PO in a.m. If target

concentrations not obtained, add 2.5 mg to a.m. dose. If after 37 days,
targets not reached, then add a 5-mg PO evening dose with titration up
to 10 mg PO b.i.d.

2/3 of total dose in morning, 1/3 in evening:

Morning dose 2:1 intermediate/rapid acting

Evening dose 1:1 intermediate/rapid acting

Insulin pumps, carbohydrate counting with use of Lispro (fast-acting insulins),

or use of Lantus (once or twice daily dosed insulin) should be undertaken with
an MFM or endocrinologist consultation. These new insulins have not yet
been approved for use in pregnancy.

Followup
Disposition
Issues for Referral
Ophthalmology for retinopathy
Endocrinology or MFM for comanagement for nontraditional insulin
therapies, and to establish good life-long diabetes care

Subspecialist, either perinatology (MFM) or pediatric cardiology, for fetal

ECHO

Perinatology regarding neonatal care

Prognosis
Pregestational DM: Excellent with strict glycemic control
Gestational DM: Excellent although increased risk for developing DM and
recurrent GDM
Complications
Progression of proliferative retinopathy
Patient Monitoring
Mother
Hemoglobin A1C for long-term glycemic control
Self-monitoring blood glucose concentrations to achieve good glycemic
control

Fetus
Antepartum fetal testing beginning in the 3rd trimester
Bibliography
ACOG Practice Bulletin No. 60. Pregestational Diabetes Mellitus. Washington DC:
ACOG; 2005.
American Diabetes Association. Standards of Medical Care in Diabetes2007.
Diabetes Care. 2007;30:S4S65.
Gabbe S, et al. Management of diabetes mellitus complicating pregnancy. Obstet
Gynecol. 2003;102:857-868.
Langer O, ed. The Diabetes in Pregnancy Dilemma, 1st ed. Lanham MD: University
Press of America; 2006.
Miscellaneous
Clinical Pearls
Preconceptional counseling and glycemic control are key to successful pregnancy
outcome.
Abbreviations
BPPBiophysical profile
DMDiabetes mellitus
CVDCardiovascular disease
ECHOEchocardiogram
EGAEstimated gestational age
GAGestational age
GDMGestational diabetes mellitus
GFRGlomerular filtration rate
MFMMaternal-fetal medicine
NSTNonstress test
NTDNeural tube defect
OGTTOral glucose tolerance test
PTLPreterm labor
AFIAmniotic fluid index
Codes
ICD9-CM
250.1 DM with ketoacidosis
250.4 DM with renal manifestations
250.5 DM with retinopathy
250.6 DM with neuropathy
648.0 DM, complicating pregnancy, childbirth, puerperium
648.8 GDM
775.0 Maternal DM affecting the fetus or newborn
Patient Teaching
Prevention
Effective contraception to prevent unintended pregnancies
Preconception counseling
Strict glycemic control prior to conception