What is the recommended approach for treating gestational diabetes with subcutaneous (SQ) insulin?

Treatment of Gestational Diabetes with Subcutaneous Insulin

Insulin remains the preferred first-line pharmacologic therapy for gestational diabetes when medical nutrition therapy fails to achieve glycemic targets, and should be initiated using an individualized basal-bolus regimen with human insulin or rapid-acting analogues (aspart, lispro) combined with NPH or long-acting analogues (detemir, glargine). 1, 2, 3

When to Initiate Insulin Therapy

Add insulin when any of the following occur despite 1-2 weeks of optimal medical nutrition therapy adherence: 3

• Fasting glucose ≥95 mg/dL
• 1-hour postprandial glucose ≥140 mg/dL
• 2-hour postprandial glucose ≥120 mg/dL
• Signs of excessive fetal growth on ultrasound

Medical nutrition therapy is the cornerstone of GDM treatment and should be attempted first for 1-2 weeks before adding pharmacotherapy. 1, 3 However, do not delay insulin initiation when glycemic targets are consistently missed, as this increases risks of macrosomia and adverse perinatal outcomes. 3

Insulin Regimen Selection

No specific insulin regimen has demonstrated superiority in GDM, so the approach should target achieving glycemic goals rather than following a rigid protocol. 1, 3 That said, a practical starting approach includes: 3

• Distribute insulin as 40% basal and 60% prandial to address the predominantly postprandial hyperglycemia characteristic of GDM
• Adjust the distribution based on glucose patterns from self-monitoring

Rapid-Acting Insulin Options

Rapid-acting analogues (aspart and lispro) are preferred for mealtime coverage as they achieve better postprandial targets with less hypoglycemia compared to regular human insulin, with similar fetal outcomes. 4, 5 These analogues have established safety profiles in pregnancy. 2, 4

• Insulin aspart is FDA-registered for meal-time use in pregnancy 6
• Insulin lispro has extensive safety data in pregnancy 5
• Insulin glulisine should be avoided as there are no reports of its use in pregnancy 5

Basal Insulin Options

For basal insulin coverage, you have several safe options: 2, 7, 4

NPH insulin is the traditional choice with the longest safety record and does not cross the placenta. 2

Insulin detemir showed improved fasting plasma glucose compared to NPH without increased hypoglycemia in head-to-head comparison, though fetal outcomes were similar. 5 This makes it a reasonable first-line long-acting analogue. 5

Insulin glargine has no clear association with adverse developmental outcomes based on published studies, though data are more limited than for detemir. 7, 5 It appears safe with similar maternal/fetal outcomes compared to NPH. 4

Insulin degludec should be avoided as current guidelines lack specific safety data for its use in pregnancy. 2

Practical Injection Technique During Pregnancy

Pregnant women with diabetes should use 4-mm pen needles given the thinning of abdominal fat from uterine expansion. 1 The abdomen remains a safe injection site throughout pregnancy when proper technique is used: 1

• First trimester: No change in insulin site or technique needed
• Second trimester: Inject over entire abdomen using properly raised skinfolds; lateral aspects can be used without skinfold
• Third trimester: Use lateral abdomen with properly raised skinfolds; alternatively use thigh, upper arm, or buttock if patient is apprehensive

For NPH and premixed insulins, gently roll horizontally between palms 10 times for 5 seconds, then tip 10 times for 10 seconds until crystals are resuspended. 1 Avoid vigorous shaking as this creates bubbles affecting accurate dosing. 1

Dosing Adjustments Throughout Pregnancy

Insulin requirements change dramatically during pregnancy, requiring frequent dose adjustments: 2

• Early pregnancy: Enhanced insulin sensitivity may require lower doses 2
• From 16 weeks onward: Requirements increase linearly, often doubling compared to pre-pregnancy needs 2
• At delivery: Requirements drop rapidly with placental delivery 2

Critical Monitoring Requirements

Self-monitor blood glucose 4-6 times daily: fasting and 1-2 hours postprandial to assess response and guide therapy. 1, 3 Do not rely on HbA1c for GDM monitoring as altered red blood cell turnover during pregnancy makes it unreliable. 3

Monitor for ketosis, especially with unexplained hyperglycemia or symptoms, as pregnancy is a ketogenic state and diabetic ketoacidosis can occur at lower glucose levels than in non-pregnant patients. 2, 8 Avoid starvation ketosis by ensuring adequate caloric and carbohydrate intake (at least 175 grams daily). 3

Ultrasound monitoring of fetal growth every 2-4 weeks starting in the second trimester detects excessive growth requiring therapy intensification. 3

Management During Labor and Delivery

For women with gestational diabetes requiring insulin (blood glucose >140 mg/dL or 8.25 mmol/L): 1

• Switch to intravenous insulin infusion during labor or cesarean section
• Continue IV insulin until return to the post-anesthesia care unit
• Provide 10% glucose infusion to avoid maternal hypoglycemia and ketosis during labor 1
• Monitor blood glucose every 1-2 hours 1

Immediate Postpartum Management

Stop insulin immediately after delivery in women with gestational diabetes. 1 Continue monitoring blood glucose before and 2 hours after meals for 48 hours. 1 Discuss treatment with a diabetologist if fasting glucose >126 mg/dL (7 mmol/L) or postprandial glucose >200 mg/dL (11 mmol/L). 1

Common Pitfalls to Avoid

Do not restrict calories excessively in an attempt to avoid insulin, as this causes ketosis which is harmful to the fetus. 3 Adequate energy intake supporting appropriate gestational weight gain per Institute of Medicine guidelines is essential. 1, 3

Do not overlook nocturnal hypoglycemia in patients with tight glucose control, especially after insulin initiation. 3 Pregnant individuals with diabetes have altered counter-regulatory responses that may decrease hypoglycemia awareness. 2, 8 Education about hypoglycemia prevention, recognition, and treatment is essential for patients and family members. 2

Do not forget aspirin prophylaxis: Prescribe low-dose aspirin 100-150 mg/day starting at 12-16 weeks gestation to lower preeclampsia risk. 2

Alternative Pharmacologic Options

While insulin is preferred, oral agents (metformin, glyburide) are acceptable alternatives for women unable or unwilling to use insulin, though this recommendation is somewhat controversial. 1 The American College of Obstetricians and Gynecologists endorses insulin as preferred first-line therapy, while SMFM and NICE guidelines support oral agents as reasonable first-line options. 1 The key consideration is that oral agents cross the placenta and long-term metabolic effects on offspring are unknown. 1