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Does Rimonabant Independently Affect Free Fatty Acid and Glucose Metabolism?
MedLine Citation:
PMID:  22170727     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Context:Endocannabinoid receptor 1 blockade is proposed to improve metabolic complications of obesity via central and peripheral effects.Objective:Our objective was to test whether rimonabant improves insulin regulation of free fatty acid and glucose metabolism after controlling for fat loss.Design:This was a double-blind, placebo-controlled substudy of the visceral fat reduction assessed by computed tomography scan on rimonabant (VICTORIA) trial.Participants and Setting:Sixty-seven abdominally obese, metabolic syndrome volunteers age 35-70 yr participated at academic medical center general clinical research centers.Intervention:Intervention included a 12-month lifestyle weight management program plus rimonabant 20 mg/d or placebo.Main Outcome Measures:Body composition and two-step euglycemic, hyperinsulinemic clamp before and after intervention were performed. Insulin sensitivity was assessed as insulin concentration needed to suppress by 50% palmitate concentration [IC(50(palmitate))], flux [IC(50(palmitate)f], and hepatic glucose output [IC(50(HGO))] and as insulin-stimulated glucose disposal (Δ glucose disappearance per Δ insulin concentration - glucose slope).Results:Body fat decreased by 4.5 ± 2.9% (SD) in the rimonabant and 1.9 ± 4.5% in the placebo group (P < 0.005). The primary [improvement in IC(50(palmitate)) and IC(50(palmitate))f] and secondary [improvement in IC(50(HGO)) and glucose slope] outcomes were not significantly different between the rimonabant and placebo groups. Post hoc analyses revealed that 1) changes in body mass index (BMI) and IC(50(palmitate)) were correlated (P = 0.005) in the rimonabant group; this relationship was not significantly different from placebo when controlling for greater BMI loss (P = 0.5); 2) insulin-regulated glucose disposal improved in both groups (P = 0.002) and correlated with changes in BMI.Conclusions:Improvements observed in insulin regulation of free fatty acid and glucose metabolism with rimonabant treatment in humans was not greater than that predicted by weight loss alone.
Authors:
Jessica Triay; Manpreet Mundi; Samuel Klein; Frederico G Toledo; Steven R Smith; Haitham Abu-Lebdeh; Michael Jensen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-14
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Mayo Clinic (J.T., M.M., H.A.-L., M.J.), Endocrinology, Rochester, Minnesota 55905; Washington University School of Medicine (S.K.), St. Louis, Missouri 63110; University of Pittsburgh (F.G.T.), Pittsburgh, Pennsylvania 15213; and Florida Hospital (S.R.S.), Winter Park, Florida 32789.
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