The effect of rosiglitazone on oxidative stress and insulin resistance in overweight individuals.

Objective: The purpose of this study was to examine the chronic effect of rosiglitazone on oxidative stress, inflammatory markers and hepatic risk factors for type 2 diabetes in overweight individuals. In addition we examined the effect of rosiglitazone on post-glucose challenge levels of glucose and insulin.

Research Design And Methods: Forty overweight individuals (BMI>27kg/m(2)) were randomized in a double blind fashion to receive 6 months treatment with either rosiglitazone 4mg/day or placebo. Primary endpoints were markers of oxidative stress (plasma peroxides), inflammatory markers (IL-6, TNF-alpha and CRP) and postprandial glucose metabolism (glucose and insulin). Secondary endpoints were changes in insulin resistance as measured by HOMA, first and second phase insulin secretion, adiponectin and effects on lipid and hepatic parameters.

Results: Plasma peroxides (-15%) decreased significantly during 6 months in the group that received rosiglitazone compared with placebo. Fasting plasma insulin concentrations decreased by 24% and HOMA increased by 35% in those receiving rosiglitazone. Plasma IL-6 (-25%), CRP (-55%) and GGT (-25%) concentrations declined significantly in the rosiglitazone group. Rosiglitazone increased plasma adiponectin by 81%. Treatment with rosiglitazone also resulted in significantly reduced first phase (-33%) and second phase (-20%) insulin release.

Conclusions: In overweight non-diabetic people rosiglitazone reduces oxidative stress and improves insulin sensitivity. Rosiglitazone also improves first and second phase insulin secretion and reduces markers of inflammation and GGT.