Incretin Hypersecretion in Gestational Diabetes Mellitus
Louise Fritsche, Martin Heni, Sabine S. Eckstein, Julia Hummel, Anette Schürmann, Hans‐Ulrich Häring, Hubert Preißl, Andreas L. Birkenfeld, Andreas Peter, Andreas Fritsche, Róbert Wágner
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 (NCT04270578). 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.