What is the recommended dose of insulin (intravenous/ subcutaneous insulin) for pregnant women with diabetes mellitus?

Insulin Dosing in Pregnancy

Insulin is the preferred medication for managing diabetes in pregnancy, with dosing requiring frequent titration as requirements typically double to triple by the third trimester, necessitating either multiple daily injections or continuous subcutaneous insulin infusion. 1, 2

Initial Insulin Requirements and Titration

Starting Doses and Early Pregnancy

• Insulin requirements often decrease in the first trimester due to enhanced insulin sensitivity, increasing the risk of hypoglycemia 2, 3
• After initial hospitalization or treatment initiation, insulin requirements may temporarily decrease before beginning their progressive rise 4
• For gestational diabetes, insulin requirements increase significantly during the initial 7±2 days of treatment until target glucose ranges are achieved 5

Progressive Increases Through Pregnancy

• Insulin requirements increase almost linearly between 2 and 9 months gestation, with the most dramatic changes occurring after 16 weeks when insulin resistance begins to increase exponentially 3, 4
• By late gestation, total daily insulin requirements typically double to triple compared to pre-pregnancy doses 2, 4
• For gestational diabetes specifically, insulin requirements rise significantly until approximately 30 weeks gestation, after which they stabilize with minimal change (approximately 3%) 5
• Insulin requirements level off toward the end of the third trimester with placental aging 3

Dosing Regimens

• Both multiple daily injections (basal-bolus regimens) and continuous subcutaneous insulin infusion (insulin pumps) are acceptable delivery strategies, with neither shown to be superior 1
• By late gestation, 95% of patients require insulin administered 2-3 times daily using combinations of regular and intermediate-acting preparations 4
• Physiologic basal-bolus dosing mimics endogenous insulin release, maintaining appropriate basal levels while providing rapid meal-related bolus coverage 6

Specific Clinical Scenarios

Type 1 Diabetes

• Women with type 1 diabetes have increased hypoglycemia risk in the first trimester due to enhanced insulin sensitivity and altered counterregulatory responses 1
• Insulin resistance drops precipitously after placental delivery, requiring immediate dose reduction 1
• Post-delivery, resume basal-bolus insulin at either 80% of pre-pregnancy doses or 50% of end-of-pregnancy doses 1

Type 2 Diabetes

• Glycemic control is often easier to achieve than in type 1 diabetes, but may require much higher insulin doses, sometimes necessitating concentrated insulin formulations 1
• For severe insulin resistance (e.g., requirements exceeding 650 units daily), U-500 concentrated insulin is an effective alternative to frequent large-volume injections 7
• Insulin requirements drop dramatically after delivery, similar to type 1 diabetes 1

Gestational Diabetes

• Insulin is indicated when lifestyle modifications fail to achieve glycemic targets 1, 6
• Strong correlation exists between insulin doses at 24 and 32 weeks (r=0.58) and between 32 and 39 weeks (r=0.99), allowing for predictable titration 5
• Emphasis on ambulatory blood glucose control and insulin adjustments should occur in the early treatment phase 5

Insulin Types and Administration

Preferred Insulin Preparations

• Human insulin preparations that do not cross the placenta are preferred 1, 2
• Insulins studied in randomized controlled trials are preferred over those studied only in cohort studies or case reports 1
• Ultra-short-acting analogs (insulin lispro or insulin aspart) improve postprandial glucose control and are considered safe and effective in pregnancy 8

Delivery Methods

• Multiple daily injections: typically 2-3 injections daily combining rapid-acting and intermediate-acting insulins 4
• Continuous subcutaneous insulin infusion: used in approximately 60% of type 1 diabetes and 10% of type 2 diabetes pregnancies 1
• Current hybrid closed-loop systems do not achieve pregnancy-specific glucose targets, though predictive low-glucose suspend technology reduces hypoglycemia risk 1

Monitoring and Adjustment Strategy

Frequency of Adjustments

• Regular evaluation of insulin requirements is necessary every 2-3 weeks as pregnancy progresses 2
• Fluctuations in insulin requirements are greatest during the third trimester 4
• A rapid reduction in insulin requirements may indicate placental insufficiency and requires immediate medical evaluation 2, 3

Glucose Monitoring

• Daily monitoring of fasting and postprandial blood glucose (4-6 times daily) is essential for insulin dose adjustments 1, 3
• Target glucose levels: fasting 70-95 mg/dL (3.9-5.3 mmol/L), 1-hour postprandial 110-140 mg/dL (6.1-7.8 mmol/L), 2-hour postprandial 100-120 mg/dL (5.6-6.7 mmol/L) 2, 3
• Continuous glucose monitoring is beneficial for improving glycemic control and reducing hypoglycemia risk 2

Special Considerations and Pitfalls

Diabetic Ketoacidosis Risk

• Pregnancy is a ketogenic state, and women with type 1 diabetes are at risk for DKA at lower blood glucose levels than when not pregnant (even <11 mmol/L or 2 g/L) 1
• Women in DKA who cannot eat often require 10% dextrose with an insulin drip to meet the higher carbohydrate demands of the placenta and fetus in the third trimester 1
• Ketone strips should be prescribed for home monitoring with education on DKA prevention and detection 1

Hypoglycemia Management

• Education for patients and family members about prevention, recognition, and treatment of hypoglycemia is essential before, during, and after pregnancy 1, 2
• Include a bedtime snack to prevent overnight hypoglycemia and accelerated ketosis 3

Postpartum Insulin Management

• Insulin requirements decrease dramatically immediately after placental delivery, with doses dropping to two-thirds of pre-pregnancy levels or one-third of late-pregnancy doses by the third postpartum day 4
• Total insulin dose typically returns to pre-pregnancy levels by the end of the first postpartum week 4
• Close monitoring and dose adjustment are needed in the immediate postpartum period to prevent hypoglycemia 2

Team-Based Care

• Due to the complexity of insulin management in pregnancy, referral to a specialized center offering team-based care is recommended (including maternal-fetal medicine specialist, endocrinologist, registered dietitian, diabetes educator, and social worker) 1