Issue 112 Item 17 Anti-Inflammatory Effect of Rosiglitazone in Obese Diabetic Pa

Rosiglitazone exerts an anti-inflammatory effect at the cellular and molecular level. We have recently demonstrated a potent anti-inflammatory effect of rosiglitazone (RSG) in obese non-diabetic subjects. We have now investigated the anti-inflammatory action in 11 obese diabetes patients who were given RSG 4 mg/day for 6 weeks. Fasting blood samples were obtained at 0, 1, 2, 4, 6 and 12 weeks.

Blood glucose concentration decreased significantly following RSG treatment, from a basal concentration of 157 ± 16 mg/dL to 127 ± 9 mg/dL at week 6 (p<0.05). Insulin concentration also significantly decreased from a basal concentration of 32.6 ± 4.6 mU/mL to 16.1 ± 2.2 mU/mL at week 6 (p<0.05). NF-kB binding activity in MNC nuclear extract fell significantly (p<0.02). This inhibition was significant by week 1 (77 ± 13% of the basal level) and continued up to week 6 (66 ± 10.6% of basal). There was a significant fall in ROS generation by MNC (p<0.05), decreasing to 94 ± 6% by week 1 and 66 ± 10% at week 6. RSG treatment reduced plasma MCP-1 (75% of the basal level; p<0.05) and CRP (70% of basal; p<0.05). FMD at baseline was 3.4 ± 1.2% and this increased significantly to 8.6 ± 1.9% (p<0.05) at week 6. Nitroglycerin-induced endothelium independent vasodilatation also increased from 11.8 ± 1.4% at baseline to 16.7 ± 2.3% at week 6 (p<0.05).

We conclude that RSG exerts a profound ROS suppressive and anti-inflammatory effect as reflected at the cellular and molecular level, and in plasma. RSG also improves vascular reactivity. These observations may have implications for atherogenesis in the long-term in patients treated with RSG.

Endo 2002 [P2-376]