Incretin Hypersecretion in Gestational Diabetes Mellitus

Abstract

Abstract Context Incretins are crucial stimulators of insulin secretion following food intake. Data on incretin secretion and action during pregnancy are sparse. Objective The aim of the study was to investigate the incretin response during an oral glucose tolerance test (OGTT) in pregnant women with and without gestational diabetes mellitus (GDM). Design We analyzed data from the ongoing observational PREG study (NCT 04270578). Setting The study was conducted at the University Hospital Tübingen. Participants We examined 167 women (33 with GDM) during gestational week 27 ± 2.2. Intervention Subjects underwent 5-point OGTT with a 75-g glucose load. Main outcome measures We assessed insulin secretion and levels of total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glicentin, and glucagon during OGTT. Linear regression was used to analyze the relation of GLP-1 and glucose with insulin secretion and the association of incretin levels on birth outcome. Results Insulin secretion was significantly lower in women with GDM (P < 0.001). Postload GLP-1 and GIP were ~20% higher in women with GDM (all P < 0.05) independent of age, body mass index, and gestational age. GLP-1 increase was associated with insulin secretion only in GDM, but not in normal glucose tolerance. Postprandial GLP-1 levels were negatively associated with birth weight. Conclusions The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.