Women with prior gestational diabetes mellitus and prediabetes are characterised by a decreased incretin effect

Diabetologia. 2017 Jul;60(7):1344-1353. doi: 10.1007/s00125-017-4265-8. Epub 2017 Mar 31.

Abstract

Aims/hypothesis: We investigated whether a reduced incretin effect, as observed in patients with type 2 diabetes, can be detected in high-risk individuals, such as women with prior gestational diabetes mellitus (pGDM).

Methods: In this cross-sectional study, 102 women without diabetes with pGDM and 15 control participants without pGDM and with normal glucose tolerance (NGT) underwent a 4 h 75 g OGTT and an isoglycaemic i.v. glucose infusion (IIGI). Women with pGDM were classified as having NGT or prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Insulin sensitivity was assessed using the Matsuda index and HOMA2-IR and the incretin effect was calculated from insulin responses during the study (100% × [AUCinsulin,OGTT - AUCinsulin,IIGI]/AUCinsulin,OGTT).

Results: Sixty-three of the 102 women with pGDM (62%) had prediabetes (median [interquartile range]: age, 38.3 [6.5] years; BMI, 32.1 [5.8] kg/m2) and 39 women (38%) had NGT (age, 39.5 [5.6] years; BMI, 31.0 [6.7] kg/m2). Control participants (n = 15) were not significantly different from the pGDM group with regards to age (39.2 [7.4] years) and BMI (28.8 [9.2] kg/m2). Compared with women with NGT and control participants, women with prediabetes had lower insulin sensitivity, as measured by the Matsuda index (3.0 [2.4] vs 5.0 [2.6] vs 1.5 [1.8], respectively; p < 0.001). The incretin effect was 55.3% [27.8], 73.8% [19.0] and 76.7% [24.6] in women with prediabetes, women with normal glucose tolerance and control participants, respectively (p < 0.01).

Conclusion/interpretation: Prediabetes was highly prevalent in women with pGDM, and alterations in the incretin effect were detected in this group before the development of type 2 diabetes.

Trial registration: clinicaltrialsregister.eu 2012-001371-37-DK.

Keywords: Gestational diabetes mellitus; Impaired glucose tolerance; Incretin effect; Isoglycaemic i.v. glucose infusion; Oral glucose tolerance test; Prediabetes; Type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Blood Glucose / analysis
  • Body Mass Index
  • Case-Control Studies
  • Cross-Sectional Studies
  • Denmark
  • Diabetes Mellitus, Type 2
  • Diabetes, Gestational / blood*
  • Diabetes, Gestational / physiopathology*
  • Double-Blind Method
  • Female
  • Glucagon / analysis
  • Glucagon-Like Peptide 1 / analysis
  • Glucose Tolerance Test
  • Humans
  • Incretins / blood*
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Prediabetic State / blood*
  • Prediabetic State / physiopathology*
  • Pregnancy
  • Prevalence

Substances

  • Blood Glucose
  • Incretins
  • Insulin
  • Glucagon-Like Peptide 1
  • Glucagon