期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 99, 期 7, 页码 2457-2466出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2013-3809
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资金
- Danish Kidney Association
- Danish Society of Nephrology
- Helen and Ejnar Bjornow Foundation
- Erik Horslev and Wife Birgit Horslev Foundation
- A.P. Moller Foundation for the Advancement of Medical Science
- Toyota Foundation
- Franz Hoffmann Foundation
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 (T-1/2), 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 T-1/2 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.
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