The Effect of a Bile Acid Sequestrant on Glucose Metabolism in Subjects With Type 2 Diabetes
- Galina Smushkin1,
- Matheni Sathananthan1,
- Francesca Piccinini2,
- Chiara Dalla Man2,
- Jennie H. Law1,
- Claudio Cobelli2,
- Alan R. Zinsmeister3,
- Robert A. Rizza1 and
- Adrian Vella1⇑
- 1Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, Minnesota
- 2Department of Information Engineering, University of Padua, Padua, Italy
- 3Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, Minnesota
- Corresponding author: Adrian Vella, .
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, placebo-controlled, 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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0923/-/DC1.
- Received July 12, 2012.
- Accepted October 12, 2012.
- © 2013 by the American Diabetes Association.
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