What is the recommended treatment for a pregnant woman with overt diabetes?

Treatment of Overt Diabetes in Pregnancy

Insulin is the mandatory and preferred treatment for pregnant women with overt diabetes, administered either as multiple daily injections or continuous subcutaneous insulin infusion. 1, 2

Primary Pharmacologic Management

Insulin Therapy

• Insulin must be used because it does not cross the placenta in measurable amounts and is the safest option for both mother and fetus 3, 4
• Both multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSIP/pump therapy) are equally acceptable delivery strategies, with neither shown to be superior during pregnancy 1
• Type 2 diabetes in pregnancy often requires much higher insulin doses than type 1 diabetes, sometimes necessitating concentrated insulin formulations 1, 2

Preferred Insulin Formulations

• Use insulin formulations with established safety profiles in pregnancy: NPH, regular insulin, or rapid-acting analogues (insulin aspart or lispro) 5, 3
• Insulin aspart has been studied in randomized controlled trials during pregnancy without demonstrating adverse maternal or fetal outcomes 4
• If a patient is already using insulin glargine before conception with good control, continuation is acceptable with close monitoring 5

Glycemic Targets

Achieve the following blood glucose targets to minimize maternal and fetal complications: 2, 3

• Fasting glucose: 70-95 mg/dL
• 1-hour postprandial: 110-140 mg/dL
• 2-hour postprandial: 100-120 mg/dL
• HbA1c: <6% if achievable without significant hypoglycemia 1, 2

Critical Monitoring Requirements

Insulin Dose Adjustments Across Pregnancy

• Insulin requirements change dramatically throughout pregnancy and require frequent titration 5, 3
• First trimester: modest decrease in insulin needs with increased hypoglycemia risk 1, 5
• Second trimester: exponential rise in insulin requirements 5, 3
• Third trimester: approximately doubling of insulin doses 5, 3
• Immediately postpartum: insulin resistance drops rapidly with placental delivery, requiring immediate dose reduction to prevent severe hypoglycemia 5, 3

Glucose Monitoring

• Daily self-monitoring of blood glucose is essential, with both fasting and postprandial measurements 3
• Continuous glucose monitoring is beneficial for improving glycemic control and reducing hypoglycemia risk 3

Adjunctive Therapies

Aspirin Prophylaxis

• Prescribe low-dose aspirin 100-150 mg/day (or 162 mg/day, available as 81 mg tablets in the U.S.) starting at 12-16 weeks gestation to reduce preeclampsia risk 1, 2, 5

Metformin Consideration

• Metformin may be considered as an alternative after discussing known risks and the need for long-term safety data 1
• An RCT showed metformin added to insulin resulted in less maternal weight gain and fewer cesarean births, but doubled the rate of small-for-gestational-age infants 1
• Metformin is contraindicated in women with hypertension, preeclampsia, or risk for intrauterine growth restriction due to potential for growth restriction or acidosis 1

Weight Management

Recommended weight gain targets for women with overt diabetes: 1, 2

• Overweight (BMI 25-29.9): 15-25 lb (6.8-11.3 kg)
• Obese (BMI ≥30): 10-20 lb (4.5-9.1 kg)
• Weight loss is not recommended due to increased risk of small-for-gestational-age infants 1

Medication Discontinuation

Immediately stop or avoid the following medications at conception or in sexually active women not using reliable contraception: 1, 2

• ACE inhibitors
• Angiotensin receptor blockers (ARBs)
• Statins
• Most non-insulin diabetes therapies

Hypoglycemia Management

Education and Prevention

• Comprehensive education on hypoglycemia prevention, recognition, and treatment is essential for patients and family members before conception, throughout pregnancy, and after delivery 1, 5
• Pregnant women with type 1 diabetes have increased hypoglycemia risk in the first trimester with altered counter-regulatory responses that decrease hypoglycemia awareness 1, 5

Ketone Monitoring

• Monitor for diabetic ketoacidosis at lower glucose thresholds during pregnancy (>200-250 mg/dL versus typical >250 mg/dL) 5, 3
• Provide home ketone strips and diabetic ketoacidosis education 2

Specialized Care and Monitoring

Multidisciplinary Team

• Referral to specialized centers offering team-based care with maternal-fetal medicine, endocrinology, nutrition, diabetes education, and social work is recommended 2, 5

Ophthalmologic Surveillance

• Baseline ophthalmology exam in first trimester with monitoring every trimester as indicated by retinopathy degree 2
• Rapid implementation of euglycemia in the setting of retinopathy is associated with worsening of retinopathy 1

Clinical Context and Risk Profile

Overt diabetes confers significantly greater risks than gestational diabetes, including: 2, 6, 7

• Spontaneous abortion
• Fetal anomalies (anencephaly, microcephaly, congenital heart disease, caudal regression)
• Preeclampsia (22% vs. 3.7% in GDM)
• Macrosomia (40% vs. 14.8% in GDM)
• Premature birth (23.1% vs. 6.7% in GDM)
• Intrauterine fetal demise
• Neonatal hypoglycemia and hyperbilirubinemia

Common pitfall: Failing to reduce insulin doses immediately after delivery can cause severe maternal hypoglycemia due to rapid decline in insulin resistance with placental removal 5, 3.