Pregnancy glucagon-like peptide 1 predicts insulin but not glucose concentrations

Incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) cause increased insulin secretion in non-pregnant adults, but their role in pregnancy, where there are additional metabolically-active hormones from the placenta, is less clear. The aim of the present study was to assess if fasting and post-load incretin concentrations were predictive of pregnancy insulin and glucose concentrations.

Pregnant women (n = 394) with one or more risk factors for gestational diabetes were recruited at 28 weeks for a 75 g oral glucose tolerance test (OGTT). Glucose, insulin, GLP-1 and GIP were measured in the fasting state and 120 min after glucose ingestion.

Fasting plasma GLP-1 concentrations were associated with plasma insulin (standardised β' 0.393 (0.289-0.498), p = 1.3 × 10^-12; n = 306), but not with glucose concentrations (p = 0.3). The association with insulin was still evident when adjusting for BMI (β' 0.271 (0.180-0.362), p = 1.1 × 10^-8; n = 297). Likewise, at 120 min the OGTT GLP-1 concentrations were associated with plasma insulin concentrations (β' 0.216 (0.100-0.331), p  = 2.7 × 10^-4; n = 306) even after adjusting for BMI (β' 0.178 (0.061-0.294), p = 2.9 × 10^-3; n = 296), but not with glucose (p  = 0.9). GIP concentrations were not associated with insulin or glucose concentrations at either time point (all p  > 0.2). In pregnancy plasma GLP-1, but not GIP, concentrations appear to be predictive of circulating insulin concentrations, independently of associations with BMIs.

These results suggest that the relationship between insulin and incretins is preserved in pregnancy, but that other factors, such as placental hormones or counter-regulatory hormones, may be more important determinants of glycaemia and gestational diabetes aetiology.