Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis

Background/Aims: Non-Alcoholic Steatohepatitis (NASH) is a chronic liver disease frequently associated with insulin resistance and type 2 diabetes mellitus (T2DM). Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH, but also leads to weight gain. To understand the nature of weight gain associated with pioglitazone treatment in NASH we analyzed 35 patients who completed tests for determination of whole body fat (WBF) and total body water (TBW). Methods: Twenty-one patients received pioglitazone and 14 placebo in a double-blind, randomized fashion for a period of 6 months. WBF and TBW were measured before and after treatment using DXA, a water dilution technique and bioimpedance. Results: Pioglitazone increased body weight (from 93.6 ± 4.2 to 96.1 ± 4.5 kg, p < 0.003) and WBF measured with DXA (from 32.9 ± 2.1 to 35.4 ± 2.5 kg, p < 0.002) while no changes were seen with placebo. Total body water was not altered significantly either after pioglitazone (from 45.4 ± 2.3 to 45.6 ± 2.7 l, p = NS) or placebo. Muscle hydration and extracellular water were unchanged both by pioglitazone and placebo treatments. Conclusions: Six months of pioglitazone treatment in patients with NASH is associated with weight gain that is attributable to an increase in adipose tissue mass and not to water retention.