Insulin clearance is altered in women with a history of gestational diabetes progressing to type 2 diabetes

Abstract

Background and aims: Insulin clearance is a relevant process in glucose homeostasis. In this observational study, we aimed to assess insulin clearance (Cl_INS) in women with former gestational diabetes (fGDM) both early after delivery and after a follow-up.

Methods and results: We analysed 59 fGDM women, and 16 women not developing GDM (CNT). All women underwent an oral glucose tolerance test (OGTT) yearly, and an insulin-modified intravenous glucose tolerance test (IVGTT) at baseline and at follow-up end (until 7 years). Both IVGTT and OGTT Cl_INS was assessed as insulin secretion to plasma insulin ratio. We also defined IVGTT first (0-10 min) and second phase (10-180 min) Cl_INS. We found that 14 fGDM women progressed to type 2 diabetes (PROG), whereas 45 women remained diabetes-free (NONPROG). At baseline, IVGTT Cl_INS showed alterations in PROG, especially in second phase (0.88 ± 0.10 l·min^-1 in PROG, 0.60 ± 0.06 in NONPROG, 0.54 ± 0.07 in CNT, p ≤ 0.03). Differences in Cl_INS were not found from OGTT. Cox regression analysis showed second phase Cl_INS as significant type 2 diabetes predictor (hazard ratio = 1.90, 95% confidence interval 1.09-3.30, p = 0.02).

Conclusion: This study showed that insulin clearance derived from an insulin-modified IVGTT is notably altered in women with history of GDM progressing towards type 2 diabetes.

Keywords: Former gestational diabetes; Incretins; Insulin clearance; Intravenous glucose tolerance test; Mathematical modelling; Oral glucose tolerance test; Type 2 diabetes.