What is the management of gestational diabetes (GDM) in obstetrics (OBGYN)?

Gestational Diabetes: Pathophysiology and OBGYN Management

Pathophysiology

Gestational diabetes mellitus (GDM) results from progressive insulin resistance during pregnancy that overwhelms pancreatic β-cell compensatory capacity, leading to maternal hyperglycemia that directly increases risks of adverse outcomes in a continuous, dose-dependent manner without clear thresholds. 1

• Pregnancy normally induces insulin resistance through placental hormones (human placental lactogen, progesterone, cortisol), particularly escalating in the second and third trimesters 2
• In GDM, pancreatic β-cells fail to adequately compensate for this increased insulin demand 2
• Maternal hyperglycemia causes fetal hyperinsulinemia, driving excessive fetal growth and metabolic complications 3
• Offspring exposed to untreated GDM develop reduced insulin sensitivity, impaired β-cell compensation, and higher likelihood of impaired glucose tolerance in childhood 3
• The relationship between glucose levels and complications is continuous—there are no safe inflection points below diagnostic thresholds 1, 3

OBGYN Management Algorithm

Step 1: Initial Management - Lifestyle Modifications (70-85% Effective)

All women with GDM must begin with medical nutrition therapy and physical activity, which successfully controls glucose in 70-85% of cases without medication. 1, 3

Medical Nutrition Therapy (MNT)

• Refer immediately to a registered dietitian nutritionist (RDN) familiar with GDM management 1
• Specific macronutrient targets: minimum 175g carbohydrate daily (35% of 2,000-calorie diet), minimum 71g protein daily, and 28g fiber daily 1, 3
• Emphasize monounsaturated and polyunsaturated fats while limiting saturated fats and completely avoiding trans fats 1
• Focus on complex, high-quality carbohydrates with low glycemic index—simple carbohydrates cause excessive postprandial excursions 1, 4
• Critical pitfall: Avoid severe carbohydrate restriction, which enhances lipolysis, elevates free fatty acids, and worsens insulin resistance; monitor fasting urine ketones to identify inappropriate restriction 1

Physical Activity

• Prescribe at least 150 minutes of moderate-intensity aerobic activity weekly, preferably spread throughout the week 1
• Effective regimens include aerobic exercise, resistance training, or both, performed 20-50 minutes daily, 2-7 days per week at moderate intensity 1
• Exercise improves glucose outcomes and reduces insulin requirements 1

Glucose Monitoring Targets

Strict glycemic targets are mandatory: 1, 3

• Fasting glucose <95 mg/dL (5.3 mmol/L)
• One-hour postprandial glucose <140 mg/dL (7.8 mmol/L) OR
• Two-hour postprandial glucose <120 mg/dL (6.7 mmol/L)

Step 2: Pharmacologic Therapy (When Lifestyle Fails)

Insulin is the only recommended first-line pharmacologic agent for GDM because it does not cross the placenta, while metformin and glyburide are explicitly NOT recommended as first-line therapy due to placental transfer and concerning long-term offspring safety data. 1, 5, 3

Insulin (First-Line Medication)

• Insulin does not cross the placenta in measurable amounts 5, 3
• Treatment with insulin improves perinatal outcomes in large randomized trials 1
• Insulin requirement typically levels off toward the end of the third trimester; a rapid reduction may indicate placental insufficiency 1

Metformin (NOT First-Line - Use Only in Exceptional Cases)

Metformin should NOT be used as first-line therapy. 1, 5, 3 Consider only when patients cannot safely use insulin and after full informed consent about risks: 5

• Placental transfer concern: Metformin readily crosses the placenta, with umbilical cord blood levels equal to or higher than maternal levels 1, 5
• Long-term offspring safety concerns:
  • 9-year-old offspring in the Auckland MiG TOFU cohort were heavier with higher waist-to-height ratios and waist circumferences compared to insulin-exposed children 1
  • Meta-analysis showed metformin exposure resulted in smaller neonates with accelerated postnatal growth, leading to higher childhood BMI 1, 5
  • 4-year-old offspring from polycystic ovary syndrome studies showed higher BMI and increased obesity 1
• Inadequate efficacy: 25-28% of women fail metformin therapy and require supplemental insulin 1, 5
• Relative advantages if used: Lower neonatal hypoglycemia risk and less maternal weight gain compared to insulin 1, 5

Sulfonylureas (Glyburide) - NOT Recommended

• Glyburide crosses the placenta (cord plasma levels 50-70% of maternal levels) 1
• Associated with increased neonatal hypoglycemia and macrosomia compared to insulin 1, 3
• Not recommended as first-line therapy 1, 3

Step 3: Monitoring and Delivery Planning

Fetal Surveillance

• For patients requiring medications or with poor glucose control, begin fetal surveillance at 32 weeks gestation 6
• Assess for fetal macrosomia (estimated fetal weight >4,000g) 6
• Discuss risks and benefits of prelabor cesarean delivery if estimated fetal weight exceeds 4,500g 6

Delivery Timing

• Diet-controlled GDM: Deliver at 39 0/7 to 40 6/7 weeks gestation 6
• Medication-controlled GDM: Deliver at 39 0/7 to 39 6/7 weeks gestation 6
• Monitor blood pressure and urinary protein at each prenatal visit due to increased hypertensive disorder risk 3

Telehealth Option

• Meta-analysis of 32 RCTs demonstrated that telehealth visits reduce cesarean delivery, neonatal hypoglycemia, macrosomia, preeclampsia, preterm birth, and other complications compared to standard in-person care 1, 3

Step 4: Postpartum Management

• Insulin resistance typically resolves after delivery 6
• Perform 75g oral glucose tolerance test 4-12 weeks postpartum to reassess glucose tolerance 7
• Reassess glucose parameters every 2-3 years if normal glucose tolerance 7
• Counsel about increased lifetime risk of type 2 diabetes and cardiovascular disease 3, 2, 7
• Recommend continued lifestyle modifications and breastfeeding to reduce diabetes risk 6

Critical Pitfalls to Avoid

• Premature medication initiation: 70-85% of women can manage GDM with lifestyle alone—avoid unnecessary pharmacologic therapy 1, 3
• Using metformin or glyburide as first-line: These agents cross the placenta and have concerning long-term offspring data; insulin is the only recommended first-line medication 1, 5, 3
• Excessive carbohydrate restriction: This worsens maternal insulin resistance through increased lipolysis and free fatty acids 1
• Inadequate RDN referral: Medical nutrition therapy requires specialized expertise in GDM management 1
• Missing postpartum follow-up: Women with GDM have substantially increased lifetime diabetes risk requiring ongoing surveillance 3, 2, 7