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

Nutr Metab Cardiovasc Dis. 2020 Jul 24;30(8):1272-1280. doi: 10.1016/j.numecd.2020.04.004. Epub 2020 Apr 10.

Abstract

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 ClINS was assessed as insulin secretion to plasma insulin ratio. We also defined IVGTT first (0-10 min) and second phase (10-180 min) ClINS. We found that 14 fGDM women progressed to type 2 diabetes (PROG), whereas 45 women remained diabetes-free (NONPROG). At baseline, IVGTT ClINS 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 ClINS 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.

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

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetes, Gestational / blood*
  • Diabetes, Gestational / diagnosis
  • Diabetes, Gestational / physiopathology
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood*
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism
  • Metabolic Clearance Rate
  • Models, Biological
  • Pregnancy
  • Risk Factors
  • Time Factors

Substances

  • Biomarkers
  • Blood Glucose
  • Insulin