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Effect of the incretin hormones on the endocrine pancreas in end-stage renal disease

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CONTEXT: The insulin-stimulating and glucagon-regulating effects of the two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), contribute to maintain normal glucose homeostasis. Impaired glucose tolerance (IGT) occurs with high prevalence among patients with end-stage renal disease (ESRD).

OBJECTIVE: To evaluate the effect of the incretin hormones on endocrine pancreatic function in patients with ESRD.

DESIGN: and Setting: Twelve ESRD patients on chronic haemodialysis and 12 matched healthy controls, all with normal oral glucose tolerance test, were included. On three separate days, a 2 h euglycaemic clamp followed by a 2 h hyperglycaemic clamp (3 mM above fasting level) was performed with concomitant infusion of GLP-1 (1 pmol/kg/min), GIP (2 pmol/kg/min) or saline administered in a randomised, double-blinded fashion. A 30% lower infusion rate was used in the ESRD group to obtain comparable incretin hormone plasma levels.

RESULTS: During clamps, comparable plasma glucose and intact incretin hormone concentrations were achieved. The effect of GLP-1 to increase insulin concentrations relative to placebo levels tended to be lower during euglycaemia in ESRD and was significantly reduced during hyperglycaemia (50 [8-72]%, P=0.03). Similarly, the effect of GIP relative to placebo levels tended to be lower during euglycaemia in ESRD and was significantly reduced during hyperglycaemia (34 [13-50]%, P=0.005). Glucagon was suppressed in both groups with controls reaching lower concentrations than ESRD patients.

CONCLUSIONS: The effect of incretin hormones to increase insulin release is reduced in ESRD which together with elevated glucagon levels could contribute to the high prevalence of IGT among ESRD patients.

Original languageEnglish
Article numberdgz048
JournalThe Journal of clinical endocrinology and metabolism
Volume105
Issue number1
ISSN0021-972X
DOIs
Publication statusPublished - Jan 2020

ID: 58130589