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Combination peroxisome proliferator-activated receptor gamma and alpha agonist treatment in Type 2 diabetes prevents the beneficial pioglitazone effect on liver fat content

Lookup NU author(s): Dr Ravikumar Balasubramanian, Dr Michael FirbankORCiD, Annette Lane, Professor Roy Taylor


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P>Aims Peroxisome proliferator-activated receptor (PPAR)-gamma and PPAR-alpha agonists individually reduce intra-organ triglyceride content and improve insulin sensitivity. However, the precise effects of combined PPAR-gamma and PPAR-alpha therapy on intra-organ triglyceride content and insulin sensitivity in subjects with Type 2 diabetes have not yet been determined. Methods Diet-controlled Type 2 subjects (n = 9) were studied before and after 16 weeks of combined PPAR-gamma [pioglitazone (PIO), 45 mg daily] and PPAR-alpha [bezafibrate (BEZA), modified release 400 mg daily] agonist therapy. Glucose metabolism and endogenous glucose production were measured following a standard liquid test meal. Liver and muscle triglyceride levels were measured by 1H magnetic resonance spectroscopy. Results Combined PIO and BEZA therapy reduced mean fasting (7.5 +/- 0.5 vs. 6.5 +/- 0.2 mmol/l, P = 0.04) and peak postprandial plasma glucose (15.3 +/- 1.1 vs. 11.7 +/- 0.6 mmol/l, P = 0.007). No significant change in hepatic or muscle triglyceride content was observed. Postprandial suppression of endogenous glucose production remained similar on both study days. Both subcutaneous and visceral fat content increased following therapy. Conclusions Combined PIO and BEZA therapy in Type 2 diabetes does not decrease intrahepatic triglyceride content or postprandial endogenous glucose production. This study demonstrates an unexpected adverse interaction of PPAR-alpha with PPAR-gamma agonist therapy.

Publication metadata

Author(s): Balasubramanian R, Gerrard J, Dalla Man C, Firbank MJ, Lane A, English PT, Cobelli C, Taylor R

Publication type: Article

Publication status: Published

Journal: Diabetic Medicine

Year: 2010

Volume: 27

Issue: 2

Pages: 150-156

ISSN (print): 0742-3071

ISSN (electronic): 1464-5491

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/j.1464-5491.2009.02906.x


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