Abstract 2773: Long-Term Administration of Thiazolidinedione Reverses Ultrasonic Manifested Atherosclerotic Processes Independent of Diabetic Improvement for Type-2 Diabetics
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 only partially clarified. We assessed hypothesis that long-term use of thiazolidinedione, an insulin sensitizer, pleiotropically inhibits atherosclerotic progression.
Methods: Forty 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 no less than 2 years. We noninvasively quantified flow-mediated dilation of brachial artery after forearm occlusion for 5 minutes(FMD), dilation of brachial artery after sublingual administration of 300 microgram 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=20) 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 decreased in group-C (p=0.03). TNG (%) also increased after medication in group-T (p=0.03) but decreased in group-C (p=0.04). IMT (mm) decreased in group-T (p=0.03) but increased in group-C (p<0.01). Changes of FMD, TNG, or IMT did not correlate to those of HbA1c (FMD: r=0.17, p=0.81, TNG: r=0.11, p=0.88, IMT: r=0.25, p=0.49).
Conclusion: These results from the ultrasonic vascular investigation indicate long-term therapy with thiazolidinedione over years improves function of arterial endothelium and smooth muscle cells, and reduces arterial wall thickness independent of reversal for clinical glucose metabolic status, which may have potential benefits for reversal of progressive atherosclerosis in type-2 diabetics.