Incretin Hypersecretion in Gestational Diabetes Mellitus

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.

Keywords: GDM; GLP-1; birth weight; incretins.