Hypoglycemia in Type 1 Diabetic Pregnancy: Role of preconception insulin aspart treatment in a randomized study

OBJECTIVE: A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy. RESEARCH DESIGN AND METHODS: IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human insulin) randomly assigned in early pregnancy (<10 weeks). NPH insulin was the basal insulin. Severe hypoglycemia (requiring third-party assistance) was recorded prospectively preconception (where possible), during pregnancy, and postpartum. Relative risk (RR) of severe hypoglycemia was evaluated with a gamma frailty model. RESULTS: Of the patients, 23% experienced severe hypoglycemia during pregnancy with the peak incidence in early pregnancy. In the first half of pregnancy, the RR of severe hypoglycemia in women randomly assigned in early pregnancy/preconception was 1.70 (95% CI 0.91–3.18, P = 0.097); the RR in the second half of pregnancy was 1.35 (0.38–4.77, P = 0.640). In women randomly assigned preconception, severe hypoglycemia rates occurring before and during the first and second halves of pregnancy and postpartum for IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS). CONCLUSIONS: These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes.