Introduction and Objective: As part of a series of studies to understand the pathogenesis of gestational diabetes mellitus (GDM) we conducted a longitudinal assessment of islet function in at-risk women during pregnancy. Methods: We measured islet function at 14-18 weeks (Visit 1) and 24-28 weeks (Visit 2) gestation in 61 women with a body mass index ≥ 30 kg/m2 who had an HbA1c ≤ 5.6% at their initial prenatal visit and no history of diabetes / prediabetes. Participants were studied after an overnight fast using a frequently sampled 3-hour, 100g oral glucose tolerance test. They were then categorized as having GDM (n=18) or normal glucose tolerance (NGT) (n=43) using Carpenter and Coustan criteria applied to the glucose values obtained at Visit 2. Results: At Visit 1 there was no difference in fasting or peak glucose between groups, but those who developed GDM exhibited a higher area above basal (AAB) glucose (545 ± 59 v 419 ± 26 mmol/180 mins, GDM vs. NGT respectively, p=0.03). Despite this, they had similar fasting glucagon concentrations (GDM 7.2 ± 0.7 v NGT 5.7 ± 0.4 pmol/L, p=0.06). Fasting C-peptide and insulin concentrations were also similar between groups at Visit 1. However, AAB C-peptide was higher in GDM (483 ± 31 v 383 ± 20 nmol/180 mins, p=0.01) as was insulin (74.1 ± 9.0 v 53.6 ± 4.6 nmol/180 mins, p=0.03). As expected at Visit 2, those with GDM had progression of their hyperglycemia with higher fasting (GDM 5.15 ± 0.13 v NGT 4.68 ± 0.04 mmol/L, p0.01) and AAB glucose (GDM 712 ± 44 v NGT 450 ± 15 mmol/180 mins, p0.01). At Visit 2, those with GDM continued to have higher integrated C-peptide (GDM 575 ± 29 v NGT 473 ± 21 nmol/180 mins, p=0.01) and insulin (GDM 84.0 ± 5.4 v NGT 63.9 ± 4.1 nmol/180 mins, p=0.01) concentrations. Conclusion: Women with GDM manifest hyperglycemia in early pregnancy before the usual time of GDM diagnosis, and this is associated with significant islet cell dysfunction. Disclosure H.E. Christie: None. S. Mohan: None. F. Boscolo: None. C. Dalla Man: Other - Webinar provider; Ended; Sanofi. Other - Joint research project; Current; Sanofi-Aventis Deutschland GmbH. A. Vella: Advisory Panel; Ended; Boehringer Ingelheim International GmbH. Advisory Panel; Current; Rezolute. Research Support; Current; Dexcom, Inc. Advisory Panel; Current; Neurotronic, Amylx. A. Egan: None. Funding National Institutes of Health DK134767
Christie et al. (Fri,) studied this question.