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Glucose-lowering ef...
Glucose-lowering effects and mechanisms of the bile acid-sequestering resin sevelamer
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Bronden, A. (author)
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Mikkelsen, K. (author)
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Sonne, D. P. (author)
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Hansen, M. (author)
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Vaben, C. (author)
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Gabe, M. N. (author)
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Rosenkilde, M. (author)
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- Tremaroli, Valentina, 1978 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Wu, Hao (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Bäckhed, Fredrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Rehfeld, J. F. (author)
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Holst, J. J. (author)
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Vilsboll, T. (author)
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Knop, F. K. (author)
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(creator_code:org_t)
- 2018-03-26
- 2018
- English.
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In: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 20:7, s. 1623-1631
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Aims Sevelamer, a non-absorbable amine-based resin used for treatment of hyperphosphataemia, has been demonstrated to have 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 after 7 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 points to a 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- antidiabetic drug
- drug mechanism
- GLP-1
- glucose metabolism
- type 2 diabetes
- farnesoid-x-receptor
- type-2 diabetes-mellitus
- metabolism
- binding
- colesevelam
- insulin
- sequestration
- release
- disease
- protein
- Endocrinology & Metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bronden, A.
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Mikkelsen, K.
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Sonne, D. P.
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Hansen, M.
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Vaben, C.
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Gabe, M. N.
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show more...
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Rosenkilde, M.
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Tremaroli, Valen ...
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Wu, Hao
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Bäckhed, Fredrik ...
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Rehfeld, J. F.
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Holst, J. J.
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Vilsboll, T.
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Knop, F. K.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetes Obesity ...
- By the university
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University of Gothenburg