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Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and β-Cell Function

OBJECTIVE: To determine the mechanism by which the bile acid sequestrant colesevelam improves glycemic control. RESEARCH DESIGN AND METHODS: We performed a frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis and a meal tolerance test (MTT) in 20 subjects with im...

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Autores principales: Marina, Anna L., Utzschneider, Kristina M., Wright, Lorena A., Montgomery, Brenda K., Marcovina, Santica M., Kahn, Steven E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329824/
https://www.ncbi.nlm.nih.gov/pubmed/22446171
http://dx.doi.org/10.2337/dc11-2050
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author Marina, Anna L.
Utzschneider, Kristina M.
Wright, Lorena A.
Montgomery, Brenda K.
Marcovina, Santica M.
Kahn, Steven E.
author_facet Marina, Anna L.
Utzschneider, Kristina M.
Wright, Lorena A.
Montgomery, Brenda K.
Marcovina, Santica M.
Kahn, Steven E.
author_sort Marina, Anna L.
collection PubMed
description OBJECTIVE: To determine the mechanism by which the bile acid sequestrant colesevelam improves glycemic control. RESEARCH DESIGN AND METHODS: We performed a frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis and a meal tolerance test (MTT) in 20 subjects with impaired fasting glucose (11 men, 9 women; mean age 60.7 ± 1.9 years, BMI 29.4 ± 0.9 kg/m(2)) in a single-blind study after 2 weeks of placebo treatment and 8 weeks of colesevelam 3.75 g daily. From these tests, insulin sensitivity, β-cell function, and glucose tolerance were determined, along with gastrointestinal peptide levels during the MTT. RESULTS: Fasting plasma glucose and HbA(1c) decreased with colesevelam (from 5.9 ± 0.1 to 5.7 ± 0.1 mmol/L, P < 0.05, and from 5.86 ± 0.06 to 5.76 ± 0.06%, P = 0.01, respectively), but fasting insulin did not change. Colesevelam had no effect on any FSIGT measures. In contrast, the MTT incremental area under the curve (iAUC) for both glucose (from 249.3 ± 28.5 to 198.8 ± 23.6 mmol/L ⋅ min, P < 0.01) and insulin (from 20,130 [13,542–35,292] to 13,086 [9,804–21,138] pmol/L ⋅ min, P < 0.05) decreased with colesevelam. However, the ratio of iAUC insulin to iAUC glucose was not changed. iAUC for cholecystokinin (CCK) increased (from 43.2 [0–130.1] to 127.1 [47.2–295.2] pmol/L ⋅ min, P < 0.01), while iAUC for fibroblast growth factor 19 decreased (from 11,185 [1,346–17,661] to 2,093 [673–6,707] pg/mL ⋅ min, P < 0.01) with colesevelam. However, iAUC for glucagon, glucose-dependent insulinotropic peptide, and glucagon-like peptide 1 did not change. CONCLUSIONS: Colesevelam improves oral but not intravenous glucose tolerance without changing insulin sensitivity, β-cell function, or incretins. This effect may be at least partially explained by the colesevelam-induced increase in CCK.
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spelling pubmed-33298242013-05-01 Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and β-Cell Function Marina, Anna L. Utzschneider, Kristina M. Wright, Lorena A. Montgomery, Brenda K. Marcovina, Santica M. Kahn, Steven E. Diabetes Care Original Research OBJECTIVE: To determine the mechanism by which the bile acid sequestrant colesevelam improves glycemic control. RESEARCH DESIGN AND METHODS: We performed a frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis and a meal tolerance test (MTT) in 20 subjects with impaired fasting glucose (11 men, 9 women; mean age 60.7 ± 1.9 years, BMI 29.4 ± 0.9 kg/m(2)) in a single-blind study after 2 weeks of placebo treatment and 8 weeks of colesevelam 3.75 g daily. From these tests, insulin sensitivity, β-cell function, and glucose tolerance were determined, along with gastrointestinal peptide levels during the MTT. RESULTS: Fasting plasma glucose and HbA(1c) decreased with colesevelam (from 5.9 ± 0.1 to 5.7 ± 0.1 mmol/L, P < 0.05, and from 5.86 ± 0.06 to 5.76 ± 0.06%, P = 0.01, respectively), but fasting insulin did not change. Colesevelam had no effect on any FSIGT measures. In contrast, the MTT incremental area under the curve (iAUC) for both glucose (from 249.3 ± 28.5 to 198.8 ± 23.6 mmol/L ⋅ min, P < 0.01) and insulin (from 20,130 [13,542–35,292] to 13,086 [9,804–21,138] pmol/L ⋅ min, P < 0.05) decreased with colesevelam. However, the ratio of iAUC insulin to iAUC glucose was not changed. iAUC for cholecystokinin (CCK) increased (from 43.2 [0–130.1] to 127.1 [47.2–295.2] pmol/L ⋅ min, P < 0.01), while iAUC for fibroblast growth factor 19 decreased (from 11,185 [1,346–17,661] to 2,093 [673–6,707] pg/mL ⋅ min, P < 0.01) with colesevelam. However, iAUC for glucagon, glucose-dependent insulinotropic peptide, and glucagon-like peptide 1 did not change. CONCLUSIONS: Colesevelam improves oral but not intravenous glucose tolerance without changing insulin sensitivity, β-cell function, or incretins. This effect may be at least partially explained by the colesevelam-induced increase in CCK. American Diabetes Association 2012-05 2012-04-11 /pmc/articles/PMC3329824/ /pubmed/22446171 http://dx.doi.org/10.2337/dc11-2050 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Marina, Anna L.
Utzschneider, Kristina M.
Wright, Lorena A.
Montgomery, Brenda K.
Marcovina, Santica M.
Kahn, Steven E.
Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and β-Cell Function
title Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and β-Cell Function
title_full Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and β-Cell Function
title_fullStr Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and β-Cell Function
title_full_unstemmed Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and β-Cell Function
title_short Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and β-Cell Function
title_sort colesevelam improves oral but not intravenous glucose tolerance by a mechanism independent of insulin sensitivity and β-cell function
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329824/
https://www.ncbi.nlm.nih.gov/pubmed/22446171
http://dx.doi.org/10.2337/dc11-2050
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