Thomas Idorn1, Filip K Knop, Morten B Jørgensen, Mikkel Christensen, Jens J Holst, Mads Hornum, Bo Feldt-Rasmussen. 1. Department of Nephrology (T.I., M.B.J., M.H., B.F.-R.), Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; Diabetes Research Division, Department of Internal Medicine (F.K.K., M.C.), Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark; and The NNF Center for Basic Metabolic Research, Department of Biomedical Sciences (F.K.K., J.J.H.), the Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Abstract
CONTEXT: The affect of the kidneys in elimination and degradation of intact incretin hormones and their truncated metabolites is unclear. OBJECTIVE: To evaluate elimination and degradation of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in patients with dialysis-dependent kidney failure. SETTING AND DESIGN:Twelve non-diabetic patients treated with chronic hemodialysis and 12 control subjects were examined in a double-blind, randomized, matched observational study at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Over 4 separate study days, synthetic human GIP or GLP-1 was infused with or without concurrent inhibition of dipeptidyl peptidase 4 using sitagliptin or placebo. Plasma concentrations of glucose, insulin, glucagon, and intact and total forms of GLP-1 or GIP were measured repeatedly. Plasma half-life (T1/2), metabolic clearance rate (MCR), area under curve, and volume of distribution for intact and metabolite levels of GLP-1 and GIP were calculated. RESULTS:Fasting concentrations of intact GLP-1 and GIP were increased in dialysis patients (P < .001) whereas fasting levels of GLP-1 and GIP metabolites did not differ between groups (P > .738). MCRs of intact GLP-1 and GIP, and the GLP-1 metabolite were reduced in dialysis patients on the placebo day (P < .009), and T1/2 of intact and metabolite forms of GLP-1 and GIP were comparable between groups (P > .121). CONCLUSIONS: Unexpectedly, degradation and elimination of the intact and metabolite forms of GLP-1 and GIP seemed preserved, although reduced, in patients with dialysis-dependent kidney failure.
RCT Entities:
CONTEXT: The affect of the kidneys in elimination and degradation of intact incretin hormones and their truncated metabolites is unclear. OBJECTIVE: To evaluate elimination and degradation of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in patients with dialysis-dependent kidney failure. SETTING AND DESIGN: Twelve non-diabeticpatients treated with chronic hemodialysis and 12 control subjects were examined in a double-blind, randomized, matched observational study at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Over 4 separate study days, synthetic humanGIP or GLP-1 was infused with or without concurrent inhibition of dipeptidyl peptidase 4 using sitagliptin or placebo. Plasma concentrations of glucose, insulin, glucagon, and intact and total forms of GLP-1 or GIP were measured repeatedly. Plasma half-life (T1/2), metabolic clearance rate (MCR), area under curve, and volume of distribution for intact and metabolite levels of GLP-1 and GIP were calculated. RESULTS: Fasting concentrations of intact GLP-1 and GIP were increased in dialysis patients (P < .001) whereas fasting levels of GLP-1 and GIP metabolites did not differ between groups (P > .738). MCRs of intact GLP-1 and GIP, and the GLP-1 metabolite were reduced in dialysis patients on the placebo day (P < .009), and T1/2 of intact and metabolite forms of GLP-1 and GIP were comparable between groups (P > .121). CONCLUSIONS: Unexpectedly, degradation and elimination of the intact and metabolite forms of GLP-1 and GIP seemed preserved, although reduced, in patients with dialysis-dependent kidney failure.
Authors: Paul B Higgins; Robert E Shade; Irám P Rodríguez-Sánchez; Magdalena Garcia-Forey; M Elizabeth Tejero; V Saroja Voruganti; Shelley A Cole; Anthony G Comuzzie; Franco Folli Journal: Am J Physiol Endocrinol Metab Date: 2016-08-16 Impact factor: 4.310