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Glucose-lowering effects and mechanisms of the bile acid-sequestering resin sevelamer

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@article{a94c5ad2f7e14b439d684b9b06b35871,
title = "Glucose-lowering effects and mechanisms of the bile acid-sequestering resin sevelamer",
abstract = "AIMS: Sevelamer, a non-absorbable amine-based resin used for treatment of hyperphosphatemia, has been demonstrated to hold a marked bile acid-binding potential alongside beneficial effects on lipid and glucose metabolism. The aim of this study was to investigate the glucose-lowering effect and mechanism(s) of sevelamer in patients with type 2 diabetes.MATERIALS AND METHODS: In this double-blinded randomized controlled trial, we randomized 30 patients with type 2 diabetes to sevelamer (n=20) or placebo (n=10). Participants were subjected to standardized 4-hour liquid meal tests at baseline and following seven days of treatment. The main outcome measure was plasma glucagon-like peptide-1 excursions as measured by area under the curve. In addition, blood was sampled for measurements of glucose, lipids, glucose-dependent insulinotropic polypeptide, C-peptide, glucagon, fibroblast growth factor-19, cholecystokinin and bile acids. Assessments of gastric emptying, resting energy expenditure and gut microbiota composition were performed.RESULTS: Sevelamer elicited a significant placebo-corrected reduction in plasma glucose with concomitant reduced fibroblast growth factor-19 concentrations, increased de novo synthesis of bile acids, a shift towards a more hydrophilic bile acid pool and increased lipogenesis. No glucagon-like peptide-1-mediated effects on insulin, glucagon or gastric emptying were evident, which point to limited contribution of this incretin hormone to the glucose-lowering effect of sevelamer. Furthermore, no sevelamer-mediated effects on gut microbiota composition or resting energy expenditure were observed.CONCLUSIONS: Sevelamer reduced plasma glucose concentrations in patients with type 2 diabetes by mechanisms that seemed to involve decreased intestinal and hepatic bile acid-mediated farnesoid X receptor activation.",
keywords = "Journal Article",
author = "Andreas Br{\o}nden and Kristian Mikkelsen and Sonne, {David P} and Morten Hansen and Christoffer V{\aa}ben and Gabe, {Maria N} and Mette Rosenkilde and Valentina Tremaroli and Hao Wu and Fredrik B{\"a}ckhed and Rehfeld, {Jens F} and Holst, {Jens J} and Tina Vilsb{\o}ll and Knop, {Filip K}",
note = "This article is protected by copyright. All rights reserved.",
year = "2018",
month = "7",
doi = "10.1111/dom.13272",
language = "English",
volume = "20",
pages = "1623--1631",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "7",

}

RIS

TY - JOUR

T1 - Glucose-lowering effects and mechanisms of the bile acid-sequestering resin sevelamer

AU - Brønden, Andreas

AU - Mikkelsen, Kristian

AU - Sonne, David P

AU - Hansen, Morten

AU - Våben, Christoffer

AU - Gabe, Maria N

AU - Rosenkilde, Mette

AU - Tremaroli, Valentina

AU - Wu, Hao

AU - Bäckhed, Fredrik

AU - Rehfeld, Jens F

AU - Holst, Jens J

AU - Vilsbøll, Tina

AU - Knop, Filip K

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/7

Y1 - 2018/7

N2 - AIMS: Sevelamer, a non-absorbable amine-based resin used for treatment of hyperphosphatemia, has been demonstrated to hold a marked bile acid-binding potential alongside beneficial effects on lipid and glucose metabolism. The aim of this study was to investigate the glucose-lowering effect and mechanism(s) of sevelamer in patients with type 2 diabetes.MATERIALS AND METHODS: In this double-blinded randomized controlled trial, we randomized 30 patients with type 2 diabetes to sevelamer (n=20) or placebo (n=10). Participants were subjected to standardized 4-hour liquid meal tests at baseline and following seven days of treatment. The main outcome measure was plasma glucagon-like peptide-1 excursions as measured by area under the curve. In addition, blood was sampled for measurements of glucose, lipids, glucose-dependent insulinotropic polypeptide, C-peptide, glucagon, fibroblast growth factor-19, cholecystokinin and bile acids. Assessments of gastric emptying, resting energy expenditure and gut microbiota composition were performed.RESULTS: Sevelamer elicited a significant placebo-corrected reduction in plasma glucose with concomitant reduced fibroblast growth factor-19 concentrations, increased de novo synthesis of bile acids, a shift towards a more hydrophilic bile acid pool and increased lipogenesis. No glucagon-like peptide-1-mediated effects on insulin, glucagon or gastric emptying were evident, which point to limited contribution of this incretin hormone to the glucose-lowering effect of sevelamer. Furthermore, no sevelamer-mediated effects on gut microbiota composition or resting energy expenditure were observed.CONCLUSIONS: Sevelamer reduced plasma glucose concentrations in patients with type 2 diabetes by mechanisms that seemed to involve decreased intestinal and hepatic bile acid-mediated farnesoid X receptor activation.

AB - AIMS: Sevelamer, a non-absorbable amine-based resin used for treatment of hyperphosphatemia, has been demonstrated to hold a marked bile acid-binding potential alongside beneficial effects on lipid and glucose metabolism. The aim of this study was to investigate the glucose-lowering effect and mechanism(s) of sevelamer in patients with type 2 diabetes.MATERIALS AND METHODS: In this double-blinded randomized controlled trial, we randomized 30 patients with type 2 diabetes to sevelamer (n=20) or placebo (n=10). Participants were subjected to standardized 4-hour liquid meal tests at baseline and following seven days of treatment. The main outcome measure was plasma glucagon-like peptide-1 excursions as measured by area under the curve. In addition, blood was sampled for measurements of glucose, lipids, glucose-dependent insulinotropic polypeptide, C-peptide, glucagon, fibroblast growth factor-19, cholecystokinin and bile acids. Assessments of gastric emptying, resting energy expenditure and gut microbiota composition were performed.RESULTS: Sevelamer elicited a significant placebo-corrected reduction in plasma glucose with concomitant reduced fibroblast growth factor-19 concentrations, increased de novo synthesis of bile acids, a shift towards a more hydrophilic bile acid pool and increased lipogenesis. No glucagon-like peptide-1-mediated effects on insulin, glucagon or gastric emptying were evident, which point to limited contribution of this incretin hormone to the glucose-lowering effect of sevelamer. Furthermore, no sevelamer-mediated effects on gut microbiota composition or resting energy expenditure were observed.CONCLUSIONS: Sevelamer reduced plasma glucose concentrations in patients with type 2 diabetes by mechanisms that seemed to involve decreased intestinal and hepatic bile acid-mediated farnesoid X receptor activation.

KW - Journal Article

U2 - 10.1111/dom.13272

DO - 10.1111/dom.13272

M3 - Journal article

VL - 20

SP - 1623

EP - 1631

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 7

ER -

ID: 52823097