Insulin antibody response to a short course of human insulin therapy in women with gestational diabetes

Abstract

Objective: To assess the insulin antibody (IA) response to human insulin (HI) therapy in women with gestational diabetes.

Research design and methods: IAs were measured by a competitive radiobinding assay in 50 women with gestational diabetes before and during treatment with HI and after delivery. At delivery, 15 maternal-cord blood sample pairs were analyzed for IA. As a reference, we searched for IA in 25 new-onset type I diabetic patients, before and at 3, 6, and 12 months after insulin therapy.

Results: Insulin autoantibodies (IAAs) were detected in 1 of 50 women with gestational diabetes and 4 of 16 type I diabetic patients (P < 0.05). At the end of pregnancy after 9.3 +/- 6.8 weeks on insulin therapy, 22 of 50 (44%) women with gestational diabetes became IA+ and 4 additional women were found to be positive 2 months postpartum. After 3 months on insulin, type I diabetic patients showed a higher rate of IA positivity (92%, P < 0.001). IA titers at the end of pregnancy were associated with the cumulative insulin dose (r = 0.29, P < 0.05). Postpartum, IA disappeared slowly in most IA+ women, but two women still showed IA 2 years after delivery Titers in cord blood were strongly related to those in maternal blood (r = 0.74, P < 0.01). The rate of adverse fetal outcome did not differ in IA and IA- mothers (27 vs. 40%, NS).

Conclusions: HI is immunogenic, and a short course of HI therapy induces IA in approximately 50% of women with gestational diabetes and 92% of type I diabetic patients. In women with gestational diabetes, insulin dose is slightly associated with IA titers. These IAs apparently cross the placenta. Fetal outcome does not differ according to the maternal IA status, and IAs disappear gradually after delivery but may remain positive for 2 years after delivery.