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

Thomas, E. Louise; Potter, Elizabeth; Tosi, Isabella; Fitzpatrick, Julie; Hamilton, Gavin; Amber, Vian; Hughes, Robert; North, Christopher; Holvoet, Paul; Seed, Mary; Betteridge, D. John; Bell, Jimmy D.; Naoumova, Rossi P.

doi:10.1016/j.atherosclerosis.2007.03.043

« Previous Next »Atherosclerosis
Volume 195, Issue 1 , Pages e181-e190, November 2007

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☆

E. Louise Thomas
- The Robert Steiner MR Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
- Corresponding author at: Robert Steiner MR Unit, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK. Tel.: +44 20 8383 3772; fax: +44 20 8383 3038.
Elizabeth Potter
- Lipid Clinic and Clinical Research Facility, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Isabella Tosi
- Lipid Clinic and Clinical Research Facility, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Julie Fitzpatrick
- The Robert Steiner MR Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Gavin Hamilton
- The Robert Steiner MR Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Vian Amber
- Division of Investigative Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Robert Hughes
- Department of Cardiology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Christopher North
- Department of Medicine, University College London, University College Hospitals, London, UK
Paul Holvoet
- Department of Cardiovascular Diseases, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium
Mary Seed
- Lipid Clinic, Charing Cross Hospital, London, UK
D. John Betteridge
- Department of Medicine, University College London, University College Hospitals, London, UK
Jimmy D. Bell
- The Robert Steiner MR Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Rossi P. Naoumova
- Lipid Clinic and Clinical Research Facility, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK

Received 12 January 2007; received in revised form 9 March 2007; accepted 23 March 2007. published online 10 May 2007.

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 30mg daily for 4 weeks, increasing to 45mg 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).