Beneficial effect of troglitazone, an insulin-sensitizing antidiabetic agent, on coronary circulation in patients with non-insulin-dependent diabetesmellitus

Evidence is increasing for small vessel remodeling and disturbance of endot helium-dependent vasodilation in diabetic patients. Insulin increases vascu lar wall thickening and produces endothelial dysfunction. Troglitazone, a n ew insulin-sensitizer antidiabetic agent, is considered to reduce plasma in sulin level and the present study assessed its effect on the coronary circu lation of the patients with non-insulin-dependent diabetes mellitus (NIDDM) . Analysis of the myocardial washout rate with adenosine triphosphate-stres s thallum-201 scintigraphy was used to estimate coronary circulation, and f or estimation of insulin sensitivity, the homeostasis model insulin resista nce index (HOMA-R) was calculated. Patients were treated with monotherapy o f either troglitazone (200 mg bid, n = 12) or glibenclamide (2.5 mg daily, n = 12) for 3 months. Age-, sex- and risk factors-matched subjects without NIDDM were employed as a control. Easting plasma glucose and hemoglobin Ale were similarly decreased by troglitazone or glibenclamide. Plasma insulin level (pmol/L) decreased from 66.6 +/- 10.8 to 39.0 +/- 7.2 with troglitazo ne, but was unchanged by glibenclamide (58.8 +/- 7.2 to 66.0 +/- 10.8). The diabetic groups had a significantly lower washout rate than controls, whic h was improved by troglitazone, but not by glibenclamide. In addition, the increase in washout rate correlated significantly with the decrease in HOMA -R in the troglitazone group. In conclusion, troglitazone can restore coron ary circulation by improving insulin resistance in patients with NIDDM.