Use of glargine in pregnant women with type 1 diabetes mellitus: A case-control study

Background: Insulin glargine is a once-daily basal insulin analog with prolonged duration of action and absence of an evident peak. Glargine is associated with reduced frequency of hypoglycemic episodes (mostly nocturnal) as well as effective glycemic control. Maintenance of good metabolic control before conception and throughout pregnancy is essential to lower the risk of fetal malformations. Glargine might be a valuable alternative in the management of pregnancies complicated by diabetes melltitus. However, because its clinical utility has not been established, the use of glargine is not currently recommended during pregnancy. Objective: The aim of this study was to retrospectively evaluate (years 2004-2007) the effectiveness and safety of insulin glargine compared with neutral protamine Hagedorn (NPH) in women affected by type 1 diabetes mellitus (T1DM) during pregnancy. Methods: The study comprised pregnant women affected by T1DM who were followed up in the Diabetes and Pregnancy Outpatient Clinic at the University of Palermo, Palermo, Italy, within 8 +/- 3.4 weeks subsequent to a positive pregnancy test. All patients with T1DM were treated with conventional basal-bolus insulin therapy (aspart or lispro analogs at the 3 main meals plus glargine or NPH at bedtime). Healthy pregnant women were used as controls for fetal and neonatal parameters. Patients were consecutively enrolled. In all women, metabolic status was determined daily by mean glycemic values (2-hour postprandial blood glucose) and glycosylated hemoglobin (HbA(1c)) values (at 3-month intervals). Fetal measurements (< 50th and > 90th centiles of the head circumference, abdomen circumference, and femoral length) were evaluated by ultrasound at second and third trimesters. Weight and femoral length were assessed at birth, and neonates were classified according to the fetal growth curve for the Italian population (< 10th centile = small for gestational age; and > 90th centile = large for gestational age (LGA). Results: A total of 73 pregnant women (30 with T1DM and 43 healthy [control]) were included in the study. Of the 30 diabetic pregnant women included in the study, 15 (mean [SD] age, 27.4 [5.2] years; mean pregravidic weight, 59.7 [11.7] kg) maintained their preconception therapy with glargine, and 15 (mean age, 30.1 [2.4] years; mean pregravidic weight, 60.7 [8.7] kg) with NPH. No significant difference was observed between the glargine-treated group and the NPH-treated group with regard to pregravidic hypertension, third-trimester preeclampsia, maternal complications and/or their progression during pregnancy (diabetic retinopathy, micro- or macroalbuminuria) and episodes of mild hypoglycemia, severe hypoglycemia, and ketosis. There were no significant between-group differences in insulin requirements (IU/kg of body weight) and glycemic profile, with the exception of better fasting and 2 hours after breakfast glycemic values in the glargine group during the first (P = 0.008 and P < 0.001, respectively) and the second (P = 0.015 and P = 0.016) trimesters, confirmed by the lower HbA(1c) levels in the first trimester (P = 0.037). The frequency of femoral length < 50th centile at both second and third trimesters was 4/15 (26.7%) in the glargine-treated group (P = 0.033 and P = 0.013, respectively, vs control), 3/15 (20.0%) and 1/15 (6.7%), respectively, in the NPH-treated group (both, P = NS vs control), and 2/43 (4.7%) and 1/43 (2.3%), respectively, in the control group. The prevalence of LGA was 7/15 (46.7%) in the glargine group (P < 0.001 vs control), 4/15 (27.6%) in the NPH group (P = 0.033 vs control), and 2/43 (4.7%) in the control group. Conclusions: Although our retrospective study involved only a small number of participants, no significant difference was found in glycemic control between glargine and NPH treatments. Use of glargine was associated with a significantly higher frequency of femoral length < 50th centile. Further larger prospective studies are necessary to assess the safety profile of glargine in T1DM during pregnancy.