The aim of this study was to examine the association between glycemia and markers of early atherosclerosis in healthy nondiabetic individuals. In 309 individuals without diabetes or symptomatic cardiovascular disease, we assessed long-term glycemia by glycosylated hemoglobin (HbA1c) and endothelial function by flow-mediated dilatation (FMD) in the brachial artery. HbA1c was negatively associated with FMD (r = -0.162, P = 0.004). Multivariate linear regression analysis after adjusting for common risk factors of cardiovascular disease showed that BMI was an effect modifier of the association between HbA1c and FMD (P = 0.034 for the HbA1c x BMI interaction). We stratified the FMD outcome data into two groups separated by the median BMI (group 1: BMI < or = 26.1 kg/m(2) and group 2: BMI > 26.1 kg/m(2)). In the lower BMI group, HbA1c was an independent predictor of FMD even when adjusted for confounding factors associated with impaired glucose metabolism (r = -0.215, P = 0.009), but in the higher BMI group HbA1c was not associated with FMD (r = -0.051, P = 0.5). In a nondiabetic population, long-term glycemia was associated with endothelial dysfunction only in lean individuals. In the overweight individuals, this association was not apparent, possibly because some of the mechanisms that mediate the effect of glycemia on vascular function are shared by obesity.