Research article summary (published 29 Sep 2009):

Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis.

Full Abstract

Pioglitazone treatment improves insulin resistance (IR), glucose metabolism, hepatic steatosis, and necroinflammation in patients with nonalcoholic steatohepatitis (NASH). Because abnormal lipid metabolism/elevated plasma free fatty acids (FFAs) are important to the pathophysiology of NASH, we examined the impact of pioglitazone therapy on adipose tissue insulin resistance (Adipo-IR) during the treatment of patients with NASH. To this end, we assessed glucose/lipid metabolism in 47 patients with impaired glucose tolerance/type 2 diabetes mellitus and NASH and 20 nondiabetic controls. All individuals underwent a 75-g oral glucose tolerance test (OGTT) in which we measured glucose tolerance, IR, and suppression of plasma FFAs. We also measured Adipo-IR index (fasting, FFAs x insulin), hepatic fat by magnetic resonance spectroscopy, and liver histology (liver biopsy). Patients were randomized (double-blind) to diet plus pioglitazone (45 mg/day) or placebo for 6 months, and all measurements were repeated. We found that patients with NASH had severe Adipo-IR and low adiponectin levels. Fasting FFAs were increased and their suppression during the OGTT was impaired. Adipo-IR was strongly associated with hepatic fat (r= 0.54) and reduced glucose clearance both fasting (r=0.34) and during the OGTT (r=0.40, all P <0.002). Pioglitazone significantly improved glucose tolerance and glucose clearance, steatosis and necroinflammation (all P<0.01-0.001 versus placebo). Fasting/postprandial plasma FFAs decreased to levels of controls with pioglitazone (P<0.02 versus placebo). Adipo-IR decreased by 47% and correlated with the reduction of hepatic fat (r=0.46, P=0.009) and with the reduction in hepatic necroinflammation (r=0.47, P=0.0007). CONCLUSION: Patients with NASH have severe Adipo-IR independent of the degree of obesity. Amelioration of Adipo-IR by pioglitazone is closely related to histological improvement and plays an important role during treatment of patients with NASH.

Author information

Author/s: Gastaldelli, Amalia (A); Harrison, Stephen A (SA); Belfort-Aguilar, Renata (R); Hardies, Lou Jean (LJ); Balas, Bogdan (B); Schenker, Steven (S); Cusi, Kenneth (K);

Affiliation: Diabetes Division, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Grants: UL 1RR025767 (Agency:NCRR NIH HHS)

Journal and publication information

Publication 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: Hepatology (Baltimore, Md.) (Hepatology), published in United States. (Language: eng)

Reference: 2009-Oct; vol 50 (issue 4) : pp 1087-93

Dates: Created 2009/10/05; Completed 2009/10/20;

PMID: 19670459, status: MEDLINE (last retrieval date: 10/20/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adipose Tissue - drug effects; metabolism; pathology Adult Blood Glucose Diabetes Mellitus, Type 2 - complications; drug therapy; metabolism Double-Blind Method Fatty Acids, Nonesterified - blood Fatty Liver - complications; drug therapy; metabolism Female Humans

Humans Hypoglycemic Agents - pharmacology; therapeutic use Insulin - metabolism Insulin Resistance - physiology Lipid Metabolism - drug effects; physiology Male Middle Aged Obesity - metabolism; pathology Thiazolidinediones - pharmacology; therapeutic use

Associated Chemicals: Blood Glucose (0) ; Fatty Acids, Nonesterified (0) ; Hypoglycemic Agents (0) ; Thiazolidinediones (0) ; Insulin (11061-68-0) ; 2,4-thiazolidinedione (2295-31-0)

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