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

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.