Beta cell function, incretin hormones, and incretin effect in obese children and adolescents with prediabetes

Abstract

Background: Defects of incretin hormones and incretin effect may be underlying mechanisms of abnormal glucose metabolism in youth. Objective: To assess incretin hormone dynamics during an oral glucose tolerance test (OGTT) and incretin effect in obese children with prediabetes in comparison with those with normal glucose tolerance (NGT). Methods: Overweight and obese children were enrolled and classified according to OGTT results as NGT and prediabetes. Insulin sensitivity, insulin secretion, incretin hormone concentrations during OGTT; and incretin effect derived from OGTT and intravenous glucose tolerance test were determined and compared between NGT and prediabetes groups. Results: Sixty-three patients (43 NGT and 20 prediabetes) were enrolled. Their median (interquartile range) age was 12.5 (11.1, 13.8) years. Peak glucagon-like peptide-1 (GLP-1) was demonstrated at 30 min during OGTT and was higher in the prediabetes group (49.2 [35.6, 63.6] versus 36.5 [27.6, 44.2] pmol/L, p = 0.009). However, incremental areas under the curves (iAUCs) of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were not different between the two groups. There was no difference in incretin effect between NGT and prediabetes (NGT: 66.5% [60.2%, 77.5%] vs. prediabetes: 70.0% [61.5%, 75.0%], p = 0.645). Incretin effect had positive correlations with iAUCs of both GLP-1 and GIP (GLP-1: r = 0.40, p = 0.004 and GIP: r = 0.37, p = 0.009). Conclusions: Comparing between obese children with prediabetes and NGT, there were no differences in overall incretin hormone changes during OGTT and incretin effect. Incretin effect was positively correlated with iAUCs of GLP-1 and GIP.