The Effect of a Bile Acid Sequestrant on Glucose Metabolism in Subjects With Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 4; pp. 1094 - 1101
• Main Authors: Smushkin, Galina, Sathananthan, Matheni, Piccinini, Francesca, Dalla Man, Chiara, Law, Jennie H., Cobelli, Claudio, Zinsmeister, Alan R., Rizza, Robert A., Vella, Adrian
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2013
• Subjects: Acids; Allylamine - analogs & derivatives; Allylamine - therapeutic use; Anticholesteremic Agents - therapeutic use; Bile; Bile acids; Biological and medical sciences; Blood Glucose - drug effects; C-Peptide - metabolism; Carbohydrates; Care and treatment; Cholesterol; Colesevelam Hydrochloride; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Female; Genetic aspects; Glucagon; Glucagon - metabolism; Glucagon-Like Peptide 1 - metabolism; Glucose; Glucose - metabolism; Humans; Insulin; Insulin - metabolism; Insulin Resistance; Male; Medical sciences; Metabolism; Middle Aged; Original Research; Peptides; Physiological aspects; Plasma; Postprandial Period; Proteins; Type 2 diabetes; United States; Endocrinopathy; Type 2 diabetes; Human; Bile acid; Metabolic diseases; Glucose; Metabolism
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db12-0923

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.