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

Background and aims: Insulin clearance is a relevant process in glucose homeostasis. In this observational study, we aimed to assess insulin clearance (ClINS) 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 ClINS 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. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.