TY - JOUR

T1 - Elimination and degradation of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with end-stage renal disease

AU - Idorn, Thomas

AU - Knop, Filip K

AU - Jørgensen, Morten B

AU - Christensen, Mikkel

AU - Holst, Jens Juul

AU - Hornum, Mads

AU - Feldt-Rasmussen, Bo

PY - 2014/4/8

Y1 - 2014/4/8

N2 - Context: The impact 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. Design and study subjects: Twelve non-diabetic patients treated with chronic hemodialysis and 12 control subjects were examined in a double-blinded, randomized, matched, observational study. Setting: Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Intervention: Over 4 separate study days, synthetic human GIP or GLP-1 was infused with or without concurrent inhibition of DPP-4 using sitagliptin or placebo. Main outcome measures: 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 < 0.001), whereas fasting levels of GLP-1 and GIP metabolites did not differ between groups (P > 0.738). MCRs of intact GLP-1 and GIP, and the GLP-1 metabolite were reduced in dialysis patients on the placebo day (P < 0.009), while T1/2 of intact and metabolite forms of GLP-1 and GIP were comparable between groups (P > 0.121). Conclusions: Unexpectedly, degradation and elimination of the intact and metabolite forms of GLP-1 and GIP appeared preserved, although reduced, in patients with dialysis-dependent kidney failure.

AB - Context: The impact 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. Design and study subjects: Twelve non-diabetic patients treated with chronic hemodialysis and 12 control subjects were examined in a double-blinded, randomized, matched, observational study. Setting: Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Intervention: Over 4 separate study days, synthetic human GIP or GLP-1 was infused with or without concurrent inhibition of DPP-4 using sitagliptin or placebo. Main outcome measures: 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 < 0.001), whereas fasting levels of GLP-1 and GIP metabolites did not differ between groups (P > 0.738). MCRs of intact GLP-1 and GIP, and the GLP-1 metabolite were reduced in dialysis patients on the placebo day (P < 0.009), while T1/2 of intact and metabolite forms of GLP-1 and GIP were comparable between groups (P > 0.121). Conclusions: Unexpectedly, degradation and elimination of the intact and metabolite forms of GLP-1 and GIP appeared preserved, although reduced, in patients with dialysis-dependent kidney failure.

U2 - 10.1210/jc.2013-3809

DO - 10.1210/jc.2013-3809

M3 - Journal article

C2 - 24712563

VL - 99

SP - 2457

EP - 2466

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

M1 - jc20133809

ER -