Abstract 2454: Long-Term Administration of Thiazolidinedione Provides Multiple Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics With Coronary Artery Disease Receiving Statin
Background: Insulin resistance and type-2 diabetes mellitus are thought to be highly involved in complex atherothrombogenic processes, but the long-term effects of insulin sensitizing agents remain partially clarified. We assessed hypothesis that long-term use of thiazolidinedi-one, an insulin sensitizer, pleiotropically inhibits atherosclerotic progression in patients treated with statin one of the standard antiatherosclerotic therapies.
Methods: Thirty type-2 diabetic patients with stable coronary artery disease were randomized to group-T where they received troglitazone (400mg/day) or pioglitazone (30mg/day), or to group-C where they continued therapy without thiazolidinedione for more than 2 years. We noninvasively quantified flow-mediated dilation of brachial artery after 5 minutes forearm occlusion (FMD), dilation of brachial artery after sublingual administration of nitroglycerin (TNG), and intima-media thickness of common carotid artery (IMT) using high-resolution ultrasonography. Changes in FMD, TNG, and IMT were compared between the 2 groups.
Results: All the patients in group-T (n=15) manifested good compliance to the treatment and improvements in diabetic variables represented by HbA1c while group-C showed no improvement. FMD (%) increased after medication in group-T (p<0.01) but remained unchanged in group-C (p=0.84). TNG (%) remained unchanged in group-T (p=0.13) and in group-C (p=0.76). IMT (mm) decreased in group-T (p=0.04) but remained unchanged in group-C (p=0.21). Changes of FMD or IMT did not correlate to those of HbA1c (FMD: r=0.20, p=0.74, IMT: r=0.25, p=0.49).
Conclusion: These results indicate long-term therapy with thiazolidinedione in diabetic patients receiving statin additionally improves endothelial function and reduces arterial wall thickness independent of reversal for clinical glucose metabolic status, which may have novel potential benefit for management of atherosclerosis in type-2 diabetics.