title: The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes.
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, 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.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Smushkin
authors.forename: Matheni
authors.initials: M
authors.lastname: Sathananthan
authors.forename: Francesca
authors.initials: F
authors.lastname: Piccinini
authors.forename: Chiara
authors.initials: C
authors.lastname: Dalla Man
authors.forename: Jennie H
authors.initials: JH
authors.lastname: Law
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
mesh_terms: D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000378:metabolism; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
chemical_list: D000924:Anticholesteremic Agents; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D000499:Allylamine; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose; D000069472:Colesevelam Hydrochloride