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

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@article{2c34720b42b64218847c8854ff52913d,
title = "Effect of the incretin hormones on the endocrine pancreas in end-stage renal disease",
abstract = "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.",
author = "J{\o}rgensen, {Morten B} and Thomas Idorn and Casper Rydahl and Hansen, {Henrik P} and Iain Bressendorff and Lisbet Brandi and {Wewer Albrechtsen}, {Nicolai J} and {van Hall}, Gerrit and Bolette Hartmann and Holst, {Jens J} and Knop, {Filip K} and Mads Hornum and Bo Feldt-Rasmussen",
note = "{\circledC} Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2020",
month = "1",
doi = "10.1210/clinem/dgz048",
language = "English",
volume = "105",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The/Endocrine Society",
number = "1",

}

RIS

TY - JOUR

T1 - Effect of the incretin hormones on the endocrine pancreas in end-stage renal disease

AU - Jørgensen, Morten B

AU - Idorn, Thomas

AU - Rydahl, Casper

AU - Hansen, Henrik P

AU - Bressendorff, Iain

AU - Brandi, Lisbet

AU - Wewer Albrechtsen, Nicolai J

AU - van Hall, Gerrit

AU - Hartmann, Bolette

AU - Holst, Jens J

AU - Knop, Filip K

AU - Hornum, Mads

AU - Feldt-Rasmussen, Bo

N1 - © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

U2 - 10.1210/clinem/dgz048

DO - 10.1210/clinem/dgz048

M3 - Journal article

VL - 105

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

M1 - dgz048

ER -

ID: 58130589