Use of Insulin Glargine During the First Weeks of Pregnancy in Five Type 1 Diabetic Women

The long-acting analog glargine is a new insulin with 24-h persistence. This peculiar peakless action profile accounts for significant risk reduction for nocturnal hypoglycemia and a more stable daily plasma glucose profile (1,2). Only a few reports have described the use of insulin glargine during human pregnancy, so its use is not recommended at present. Animal studies have addressed the safety and efficacy of glargine during pregnancy, showing no direct effect on reproduction and embryo-fetal development (3,). Recently, Devlin et al. (4) and Holstein et al. (5) reported the use of insulin glargine in two type 1 diabetic women; both cases were free of any pregnancy complications and with no direct effect on embryogenesis.

We report on five case subjects who used glargine during unplanned pregnancy (Table 1). All five diabetic women attended their first diabetes evaluation at our Outpatient Clinic between November 2002 and February 2004. None had evidence of retinopathy or autonomic neuropathy and they had normal urinary albumin excretion. They initiated glargine 5–12 months before conception because of frequent nocturnal hypoglycemia and suboptimal glycemic control. Insulin glargine was started as part of a basal-bolus regimen with an average dose of 25 ± 17 IU/day (range 14–56) given as a single predinner subcutaneous injection. The first diabetes assessment after commencement of pregnancy occurred at the 6th gestational week in three cases, while the remaining women were seen at the 8th and 12th week of gestation, respectively. Their HbA_1c at that time was 7.3 ± 0.8%. Due to the lack of controlled data on the safety and efficacy of glargine in pregnant women, all patients were switched to NPH in the morning and bedtime, along with the usual premeal insulin therapy. After 2 weeks of the new insulin regimen, three women were started on continuous subcutaneous insulin infusion because optimal control could not be attained. In all five patients, strict glycemic control was achieved, with an average HbA_1c of 6.0 ± 0.2% at the end of pregnancy. Pre-eclampsia developed in one patient at the 32nd week of gestation, and neither progression in retinopathy nor other microangiopatic complications were detected. Previous observations have reported that the use of glargine is associated with worsening eye disease in type 2 diabetic women (2). Babies (two males and three females) were delivered at a mean gestational age of 36.6 ± 1.1 weeks by cesarean section in all but one woman. Mean birth weight was 3,066 ± 898 g, with one baby >4 kg, whereas the other four babies’ weights were adequate for gestational age. There was neither major nor minor congenital malformation, and none of the babies had any complications during the postpartum period.

Our experience is limited to a few subjects; nevertheless, all the observed women used insulin glargine from the preconception period to 6–12 weeks’ postconception. Hyperglycemia during the first 8 weeks of gestation, as clearly reported by Mills et al. (6), increases the risk of congenital anomalies. In our report, insulin glargine does not seem to affect embryo-fetal development in this critical period of embryogenesis. However, the small number of women and the early discontinuation of therapy with insulin glargine do not allow us to draw any final conclusion. Nevertheless, this observation, as well as other anecdotic observations, emphasizes the need for properly planned investigations.