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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 2 incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), contribute to maintain normal glucose homeostasis. Impaired glucose tolerance 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 hemodialysis and 12 matched healthy controls, all with normal oral glucose tolerance test, were included. On 3 separate days, a 2-hour euglycemic clamp followed by a 2-hour hyperglycemic 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 randomized, 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 euglycemia in ESRD and was significantly reduced during hyperglycemia (50 [8-72]%, P = 0.03). Similarly, the effect of GIP relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (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 impaired glucose tolerance among ESRD patients.

Original languageEnglish
Article numberdgz048
JournalThe Journal of clinical endocrinology and metabolism
Volume105
Issue number3
Pages (from-to)E564-E574
ISSN0021-972X
DOIs
Publication statusPublished - Mar 2020

    Research areas

  • Adult, Denmark, Double-Blind Method, Female, Glucagon-Like Peptide 1/administration & dosage, Glucagon/blood, Glucose Clamp Technique, Glucose Tolerance Test, Humans, Incretins/administration & dosage, Insulin Secretion/drug effects, Insulin/metabolism, Islets of Langerhans/drug effects, Kidney Failure, Chronic/metabolism, Male, Middle Aged, Renal Dialysis

ID: 58130589