Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: Relation to liver, muscle and regional body fat content

Abstract

Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder conferring high risk of premature atherosclerosis, characterized by high cholesterol and/or triglyceride, low high density lipoprotein (HDL) cholesterol and insulin resistance. We examined whether pioglitazone, added to conventional lipid-lowering therapy, would favourably affect metabolic parameters and alter body fat content. We undertook a randomized, double blind, placebo-controlled study in 22 male patients with FCHL treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, increasing to 45 mg for 12 weeks. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed to measure adipose tissue (AT) body content as well as intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) at baseline and after treatment. Significantly improved in the pioglitazone group were: triglyceride/HDL (atherogenic index of plasma) −32.3% ( p = 0.002), plasma glucose −4.4% ( p = 0.03), alanine-aminotransferase (ALT) −7.7% ( p = 0.005) and adiponectin 130.1% ( p = 0.001). Pioglitazone treatment resulted in a significant increase in total (5.3%, p = 0.02) and subcutaneous (7.1%, p = 0.003) adipose tissue as well as in soleus-IMCL levels (47.4%, p = 0.02) without alteration in intra-abdominal AT or IHCL. Changes in ALT and AST and IHCL were strongly correlated ( r = 0.72, p < 0.01; r = .0.86, p < 0.01, respectively). In patients with FCHL on conventional lipid-lowering therapy, the addition of pioglitazone acts favourably on several metabolic parameters.