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Patients with diabetes mellitus are known to be at increased risk for acute cardiovascular events. We used intravascular ultrasound virtual histology (IVUS-VH) to examine whether nonobstructive coronary artery lesions of diabetic patients have distinct plaque composition and morphology compared with nondiabetic patients.A total of 41 patients (13 diabetic and 28 nondiabetic) with proximally located angiographically nonobstructive coronary lesions were prospectively enrolled. In addition to plaque geometry, IVUS-VH lesion evaluation of the fibrous, fibro-fatty, necrotic core and calcified plaque components was performed. An IVUS-derived thin-cap fibroatheroma (IDTCFA) was defined as a lesion with a confluent necrotic core of at least 10% lumen cross-sectional area without evident overlying fibrous tissue and a plaque atheroma volume of at least 40% in at least three consecutive frames.Coronary artery lesions of diabetic and nondiabetic patients had similar plaque geometry. Lesions of diabetic patients were more likely to be positively remodeled than those of nondiabetic patients (67 vs. 27%, respectively, P = 0.02). Plaques of diabetic patients had significantly higher necrotic core percentages (23.3 ± 6.1 vs. 17.1 ± 8.7%, P = 0.03) and lower fibro-fatty tissue percentages (8 ± 5 vs. 14.2 ± 7.5%, P = 0.01) than those of nondiabetic patients. In addition, IDTCFAs were significantly more prevalent at the minimal lumen area site of diabetic patients compared to nondiabetic patients (92 vs. 54%, respectively, P = 0.02). After adjustment for various confounders, diabetes mellitus remained as the only independent clinical predictor of IDTCFAs at the minimal lumen area site [odds ratio (OR) 9.43, 95% confidence interval (CI) 1.06–84.04, P = 0.04].Nonobstructive coronary artery lesions of diabetic patients have distinct compositional and morphological features, suggesting that these differences may explain the increased likelihood of coronary events in diabetic patients.