Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity

Insulin secretion rates an greater after oral glucose than after parenteral administration of an equivalent glucose load. This augmented beta-cell sec retory response to an oral glucose load results from the release of mainly two gut hormones: gastric inhibitory polypeptide (GIP) and glucagon-like pe ptide-1, which potentiate glucose-induced insulin secretion. Because of the ir insulinotropic action, their abnormal secretion may be involved in the p athogenesis of the hyperinsulinemia of childhood obesity. In this study, we used the hyperglycemic clamp with a small oral glucose load to assess the effect of childhood obesity on GIP response in seven prepubertal lean and I I prepubertal obese children and in 14 lean adolescents and 10 obese adoles cents. Plasma glucose was acutely raised to II mM by infusing i.v. glucose and kept at this concentration for 180 min. Each subject ingested oral gluc ose (30 g) at 120 min, and the glucose infusion was adjusted to maintain th e plasma glucose plateau. Basal insulin and C-peptide concentrations and in sulin secretion rates (calculated by the deconvolution method) were signifi cantly greater in obese children compared with lean children (p < 0.001). S imilarly, during the first 120 min of the clamp, insulin secretion rates we re higher in obese than lean children. After oral glucose, plasma insulin, C-peptide, and insulin secretion rates further increased in all four groups . This incretin effect was 2-fold greater in obese versus lean adolescents (p < 0.001). Circulating plasma GIP concentrations were similar at baseline in all four groups and remained unchanged during the first 120 min of the clamp. After oral glucose, plasma GTP concentrations rose sharply in all gr oups (p < 0.002). Of note, the rise in GTP was similar in both lean and obe se children. In conclusion, under conditions of stable hyperglycemia, the i ngestion of a small amount of glucose elicited equivalent GIP responses in both lean and obese children. However, despite similar GIP responses, insul in secretion was markedly augmented in obese adolescents. Thus, in juvenile obesity, excessive alimentary beta-cell stimulation may be independent of the increased release of GIP.