Abstract 2221: Long-Term Administration of Thiazolidinedione Provides Multiple Ultrasonic Manifested Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics Receiving Angiotensin-II Receptor Blocker

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 thiazolidinedione, an insulin sensitizer, pleiotropically inhibits atherosclerotic progression in patients treated with angiotensin-II receptor blocker, one of the best possible antiatherosclerotic therapies. Methods: Thirty-two type-2 diabetic patients treated with angiotensin-II receptor blocker 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 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: Group-T (n=16) manifested improvements in diabetic variables while group-C showed no improvement. FMD (%) increased after medication in group-T (p<0.01) but remained unchanged in group-C (p=0.86). TNG (%) remained unchanged in both groups. IMT (mm) decreased in group-T (p=0.03) but remained unchanged in group-C (p=0.12). Changes of FMD or IMT in group-T did not correlate to those of HbA1c (FMD: r=0.21, p=0.70, IMT: r=0.22, p=0.62). Conclusion: These results indicate long-term therapy with thiazolidinedione in diabetic patients receiving angiotensin-II receptor blocker additionally improves endothelial function, and reduces arterial wall thickness independent of reversal for diabetic status, which may have novel potential benefit for management of atherosclerosis in type-2 diabetics treated with standard antiatherosclerotic therapies.