Enhanced glucagon-like peptide-1 (GLP-1) response to oral glucose in glucose-intolerant HIV-infected patients on antiretroviral therapy

Abstract

Objectives: We investigated whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are major regulators of glucose tolerance through the stimulation of insulin secretion, contribute to impaired glucose tolerance (IGT) among HIV-infected patients on highly active antiretroviral therapy (HAART). Methods: Eighteen HIV-infected male patients (six lipodystrophic and 12 nonlipodystrophic) with normal glucose tolerance (NGT) were compared with 10 HIV-infected male patients (eight lipodystrophic and two nonlipodystrophic) with IGT. Plasma concentrations of GLP-1 and GIP were determined frequently during a 3-h, 75-g glucose tolerance test. Insulin secretion rates (ISRs) were calculated by deconvolution of C-peptide concentrations. Results: The incremental area under the curve (incrAUC) for GLP-1 was increased by 250% in IGT patients compared with NGT patients (1455 ± 422 vs. 409 ± 254 pmol/L/180 min, respectively; P < 0.05), whereas the incrAUC for GIP did not differ between the study groups (7689 ± 1097 vs. 8041 ± 998 pmol/L/180 min, respectively; not significant). In pooled study groups, the GIP incrAUC correlated positively with the ISR incrAUC without adjustment (r = 0.38, P < 0.05) and following adjustment for glucose incrAUC (r = 0.49, P < 0.01). Conclusions: Our data suggest: (1) that glucose-intolerant, HIV-infected male patients may display enhanced GLP-1 responses to oral glucose compared with normal glucose-tolerant HIV-infected male patients, which may represent a compensatory mechanism rather than explain the IGT; (2) that the GIP response may be associated with ISR independently of plasma glucose in nondiabetic HIV-infected males on HAART. © 2005 British HIV Association.