Effects of pioglitazone and metformin on intracellular lipid content in liver and skeletal muscle of individuals with type 2 diabetes mellitus

Both ectopic fat accumulation and changes of the amount of several adipocyte secreting proteins (adipokines) are thought to contribute to the development of insulin resistance associated with obesity and type 2 diabetes mellitus. We have now investigated the effects of 2 insulin-sensitizing drugs, pioglitazone and metformin, on body fat composition and serum adipokine concentrations in individuals with type 2 diabetes mellitus. A total of 41 diabetic patients were treated with pioglitazone (n =21) or metformin (n =20) for 6 months. Intramyocellular lipid content (IMCL) and hepatic lipid content as well as the areas of subcutaneous and visceral fat deposits in the abdomen were determined by nuclear magnetic resonance spectroscopy before and after drug treatment. The serum concentrations of adiponectin and retinol binding protein 4 were also determined by enzyme-linked immunosorbent assays. Pioglitazone treatment reduced both hepatic lipid content (12.0 ± 6.1 vs 8.4 ± 3.7 arbitrary units [AU], P < .01) and IMCL (8.4 ± 3.6 vs 6.3 ± 2.4 AU/creatine, P < .01), whereas metformin reduced only IMCL (7.0 ± 3.6 vs 5.8 ± 2.0 AU/creatine, P < .05). Although the areas of visceral and subcutaneous fat were not significantly affected by treatment with either drug, pioglitazone induced a significant reduction in the ratio of visceral to subcutaneous fat area (0.92 ± 0.41 vs 0.85 ± 0.41, P < .05). Pioglitazone treatment also resulted in a marked increase in serum adiponectin concentration (5.6 ± 4.1 vs 16.2 ± 9.9 μg/mL, P < .0001) and a small but significant decrease in serum retinol binding protein 4 concentration (73.4 ± 25.1 vs 65.1 ± 23.7 μg/mL, P < .05). These results suggest that pioglitazone may improve insulin sensitivity both by affecting serum adipokine concentrations and by reducing the intracellular triglyceride content of liver and skeletal muscle in individuals with type 2 diabetes mellitus.