Insulin is known to stimulate proliferation and migration of vascular smooth muscle cells. As the predominant mechanism of restenosis after stent implantation is neointimal tissue proliferation, one can expect a relationship between hyperinsulinemia and restenosis in these patients. The aim of this study was to determine whether hyperinsulinemia during oral glucose tolerance test is a predictor of the development of restenosis after stent implantation in nondiabetic patients. We prospectively studied 52 nondiabetic patients with effort angina who underwent elective stent implantation for single-vessel coronary artery disease. In order to increase the statistical power of the study, numerous exclusion criteria were applied. All patients were subjected to a 75 g oral glucose tolerance test a day before the stent implantation and underwent follow-up angiography 6 months later. Plasma insulin levels in fasting (6.77 +/- 1.57 vs. 5.36 +/- 1.35 muU/ml; P = 0.005), at 30 min (102.48 +/- 10.6 vs. 47.74 +/- 12.75 muU/ml; P = 0.001), 1 hr after (120.23 +/- 14.1 vs. 63.08 +/- 12.62 mu/ml; P = 0.001), 2 hr after (63.58 +/- 8.64 vs. 34.88 +/- 6.82 mu/ml; P = 0.001), and 3 hr after (25.71 +/- 5.65 vs. 23.02 +/- 4.61 mu/ml; P = 0.04) loading were significantly higher in patients with stent restenosis than in patients without stent restenosis. Insulin area and insulin area/glucose area were also significantly higher in patients with stent restenosis than in patients without (219.5 +/- 23.8 vs. 118.9 +/- 21.8, P = 0.001, and 0.62 +/- 0.09 vs. 0.33 +/- 0.06, P = 0.001, respectively). By multiple logistic regression analysis, insulin area during oral glucose tolerance test was found to be an independent predictor of stent restenosis (OR = 1.12; 95% CI = 1.01-1.25; P = 0.031). In conclusion, nondiabetic patients with hyperinsulinemia during oral glucose tolerance test have a high risk for restenosis after stent implantation, and performing this simple test before intervention may be useful for the prediction of stent restenosis.