The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes

Galina Smushkin, Matheni Sathananthan, Francesca Piccinini, Chiara Dalla Man, Jennie H. Law, Claudio Cobelli, Alan R. Zinsmeister, Robert A. Rizza, Adrian Vella

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53 Scopus citations

Abstract

We designed an experiment to examine the effect of bile acid sequestration with Colesevelam on fasting and postprandial glucose metabolism in type 2 diabetes. To do so, we tested the hypothesis that Colesevelam increases the disposition index (DI), and this increase is associated with increased glucagon-like peptide-1 (GLP-1) concentrations. Thirty-eight subjects on metformin monotherapy were studied using a double-blind, placebocontrolled, parallel-group design. Subjects were studied before and after 12 weeks of Colesevelam or placebo using a labeled triple-tracer mixed meal to measure the rate of meal appearance (Meal Ra), endogenous glucose production (EGP), and glucose disappearance (Rd). Insulin sensitivity and β-cell responsivity indices were estimated using the oral minimal model and then used to calculate DI. Therapy with Colesevelam was associated with a decrease in fasting (7.0 ± 0.2 vs. 6.6 ± 0.2 mmol/L; P = 0.004) and postprandial glucose concentrations (3,145 ± 138 vs. 2,896 ± 127 mmol/6 h; P = 0.01) in the absence of a change in insulin concentrations. Minimal model-derived indices of insulin secretion and action were unchanged. Postprandial GLP-1 concentrations were not altered by Colesevelam. Although EGP and Rd were unchanged, integrated Meal Ra was decreased by Colesevelam (5,191 ± 204 vs. 5,817 ± 204 μmol/kg/6 h; P = 0.04), suggesting increased splanchnic sequestration of meal-derived glucose.

Original languageEnglish (US)
Pages (from-to)1094-1101
Number of pages8
JournalDiabetes
Volume62
Issue number4
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Smushkin, G., Sathananthan, M., Piccinini, F., Man, C. D., Law, J. H., Cobelli, C., Zinsmeister, A. R., Rizza, R. A., & Vella, A. (2013). The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes. Diabetes, 62(4), 1094-1101. https://doi.org/10.2337/db12-0923