200-OR: Postpartum Islet-Cell Function in Individuals With and Without Gestational Diabetes

Gestational diabetes mellitus (GDM) affects approximately 10% of pregnancies. Although 60% individuals with GDM develop a disorder of glucose metabolism by 10 years postpartum, preventive care is lacking as the mechanisms leading to overt diabetes following pregnancy remain elusive. As part of a series of studies to understand the pathogenesis of GDM, we examined islet function at 3, 6 and 12 months postpartum. We included women with (n=10), and without (n=10) GDM in the preceding pregnancy. There were no differences in age, body mass index, or lean body mass between groups. At each study visit, subjects presented following an overnight fast and ingested a 75g oral glucose solution at time 0. Venous blood was drawn fasting and at frequent intervals over 180 minutes for measurement of glucose and hormone concentrations. At 3 months postpartum, those with GDM had higher fasting glucose (4.9 ± 0.1 v 4.5 ± 0.1 mmol/L, GDM vs normal respectively, p=0.04) but no differences in peak / integrated glucose compared to those without. Fasting insulin (31 ± 6 vs 14 ± 1 pmol/L, p=0.01) and C-peptide (0.64 ± 0.09 vs 0.44 ± 0.02 mmol/L, p=0.04) were higher in those with GDM with no differences in peak / integrated concentrations. Fasting (4.9 ± 0.4 vs 3.4 ± 0.3 pmol/L, p=0.01) and area under the curve (398 ± 21 v 340 ± 11pmol / 180 min, p=0.03) glucagon were higher in those with GDM. At 6 and 12 months postpartum, these differences were no longer evident with similar glucose and hormone concentrations between groups. These data suggest that both α- and β-cell dysfunction likely contribute to GDM with residual dysfunction present at 3 months postpartum. This is no longer evident by 6 months postpartum. Further longitudinal work is needed to determine progression of fasting and post-challenge islet cell function throughout pregnancy and postpartum to understand how those with GDM are primed for early onset type 2 diabetes. Disclosure A.M. Egan: None. H.E. Christie: None. S. Mohan: None. A. Vella: Research Support; Novo Nordisk. Consultant; Hanmi Pharm. Co., Ltd., Crinetics Pharmaceuticals, Inc. Advisory Panel; Rezolute, Inc. Funding National Institutes of Health (K23DK134767)