Circulating levels of incretin hormones and amylin in the fasting state and after oral glucose in GH-deficient patients before and after GH replacement: a placebo-controlled study

Objective: Hyperinsulinemia in association with GH excess is considered a c ompensatory response to insulin resistance, but the possibility of alternat ive insulinotropic mechanisms has not been investigated in vivo . It is als o unknown how GH influences the secretion from pancreatic beta -cells of am ylin, a peptide which regulates prandial glucose homeostasis and may be lin ked to development of beta -cell dysfunction. We therefore measured plasma concentrations of two gut insulinotropic hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin-releasing peptide (GIP), and total as well as noa-glycosylated amylin, in 24 GH- deficient adults before and aft er 4 months of GH replacement (daily evening injections of 2 IU GH/m(2)). Design: Double-blind, placebo-controlled, parallel study. Methods: All participants underwent an oral glucose tolerance test (OGTT) a t 0 and 4 months. Results: A 33% suppression of fasting GLP-1 concentrations was measured in the GH group at 4 months (P = 0.02), whereas a non-significant increase occ urred in the placebo group (P = 0.08). Fasting levels of CIP and amylin did not change significantly after 4 months in either group. The incremental r esponse in GLP-1 during the OGTT was significantly lower after GH treatment as compared with both baseline (P = 0.02) and the response in the placebo group (P = 0.03), The stimulation of GIP secretion following OGTT was simil ar on all occasions. The OGTT-induced incremental response in non-glycosyla ted amylin was moderately elevated after GH treatment as compared with plac ebo (P = 0.05). Plasma concentrations of glucose and insulin, both in the f asting state and after the OGTT, were higher after GH treatment, but the ra tio between amylin and insulin remained unchanged. Conclusions: GH-induced hyperinsulinemia is accompanied by proportionate el evations in amylin concentrations and a blunting of gut GLP-1 secretion. Th e mechanisms underlying the suppression of GLP-1 remain to be elucidated.