To the Editor: The management of pregnant women with pre-existing diabetes is often challenging for clinicians.

A 38-year-old woman presented with an unplanned pregnancy at 8 weeks’ gestation. She had a 4-year history of type 2 diabetes treated with metformin, which she stopped taking on confirmation of her pregnancy. Her glycated haemoglobin (HbA1c) level was 9.0% at her first antenatal visit, and therapy with pre-meal insulin aspart and twice daily isophane was commenced. Her insulin requirement rapidly escalated, rising to 400 units per day by the end of the first trimester. Metformin therapy was reintroduced in the second trimester. Despite strategies including splitting her insulin doses and trialling different insulin regimens, control of her diabetes remained poor.

At 30 weeks’ gestation, U-500 insulin became available, and that allowed rapid titration of insulin doses (Box). Her HbA1c level improved to 6.4% in the third trimester. At 35 weeks, her daily insulin requirement had reached 1455 units and her membranes ruptured prematurely. During labour, an intravenous insulin infusion rate of 90 units per hour was needed to achieve normoglycaemia. At birth, the neonate weighed 2005 g (11th percentile) with no evidence of congenital abnormalities, but she suffered transient hypoglycaemia on Day 1. Postpartum, the mother’s daily insulin requirement decreased to 28 units per day.

In pregnant women with pre-existing type 2 diabetes, the insulin requirement increases substantially in the second half of pregnancy.1 In the past 12 months, among 25 pregnant women with type 2 diabetes who attended our antenatal clinic, the median insulin dose at the end of their pregnancies was 123 units per day, with 6 women requiring doses exceeding 200 units per day. At daily doses above 200 units, the therapeutic response to further increments in the insulin dose is attenuated.2 Current insulin preparations in Australia (100 units/mL) can be problematic for these patients as it is difficult to administer large volumes of insulin subcutaneously.

U-500 is a preparation of regular insulin at a concentration of 500 units/mL. It is invaluable for patients with extreme insulin resistance, as a smaller volume is needed for injections. Its application during pregnancy has been previously reported.3-5 U-500 insulin is not readily available in Australia, and the preparation has to be administered by syringe. Hence, the volume of insulin must be drawn up accurately, as insulin syringes in Australia are designed for conventional lower-concentration insulin preparations (100 units/mL).

This case highlights one of the many difficulties in managing pregnant women with pre-existing diabetes. The use of U-500 may be considered for women on extremely large doses of insulin and whose diabetes is still suboptimally controlled. The safety aspects of U-500 during pregnancy will need further examination.

Insulin requirements during pregnancy of a 38-year-old woman with diabetes