Document Detail


Pioglitazone in the treatment of NASH: the role of adiponectin.
MedLine Citation:
PMID:  20662773     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Plasma adiponectin is decreased in NASH patients and the mechanism(s) for histological improvement during thiazolidinedione treatment remain(s) poorly understood.
AIM: To evaluate the relationship between changes in plasma adiponectin following pioglitazone treatment and metabolic/histological improvement.
METHODS: We measured in 47 NASH patients and 20 controls: (i) fasting glucose, insulin, FFA and adiponectin concentrations; (ii) hepatic fat content by magnetic resonance spectroscopy; and (iii) peripheral/hepatic insulin sensitivity (by double-tracer oral glucose tolerance test). Patients were then treated with pioglitazone (45 mg/day) or placebo and all measurements were repeated after 6 months.
RESULTS: Patients with NASH had decreased plasma adiponectin levels independent of the presence of obesity. Pioglitazone increased 2.3-fold plasma adiponectin and improved insulin resistance, glucose tolerance and glucose clearance, steatosis and necroinflammation (all P < 0.01-0.001 vs. placebo). In the pioglitazone group, plasma adiponectin was significantly associated (r = 0.52, P = 0.0001) with hepatic insulin sensitivity and with the change in both variables (r = 0.44, P = 0.03). Increase in adiponectin concentration was related also to histological improvement, in particular, to hepatic steatosis (r = -0.46, P = 0006) and necroinflammation (r = -0.56, P < 0.0001) but importantly also to fibrosis (r = -0.29, P = 0.03).
CONCLUSIONS: Adiponectin exerts an important metabolic role at the level of the liver, and its increase during pioglitazone treatment is critical to reverse insulin resistance and improve liver histology in NASH patients.
Authors:
A Gastaldelli; S Harrison; R Belfort-Aguiar; J Hardies; B Balas; S Schenker; K Cusi
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Alimentary pharmacology & therapeutics     Volume:  32     ISSN:  1365-2036     ISO Abbreviation:  Aliment. Pharmacol. Ther.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8707234     Medline TA:  Aliment Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  769-75     Citation Subset:  IM    
Copyright Information:
2010 Blackwell Publishing Ltd.
Affiliation:
The University of Texas Health Science Center at San Antonio, 78284-3900, USA.
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
UL 1RR025767/RR/NCRR NIH HHS

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