OBJECTIVE: The current study was designed to test the acute effects of dietary advanced glycation end products (AGEs) on endothelial function of diabetic and nondiabetic subjects. RESEARCH DESIGN AND METHODS: Flow-mediated dilation (FMD) of the brachial artery and serum levels of AGEs, plasminogen activator inhibitor 1 (PAI-1), vascular cell adhesion molecule 1 (VCAM-1), and glucose were assessed before and after a single oral AGE challenge (approximately 1.8 x 10(6) AGE units) in 44 diabetic and 10 nondiabetic subjects. RESULTS: The diabetic patients had higher baseline levels of serum AGEs (P = 0.020), PAI-1 (NS), and VCAM-1 (P = 0.033) and lower baseline values of FMD compared with nondiabetic subjects (P = 0.032). Ninety minutes after a single oral AGE challenge, serum AGEs and PAI-1 levels increased and FMD decreased significantly in both healthy subjects (AGEs: 7.2 +/- 0.5 to 9.3 +/- 1 units/ml, P = 0.014; PAI-1: 5.4 +/- 0.4 to 6.8 +/- 0.4 ng/ml, P = 0.007; and FMD: 9.9 +/- 0.7 to 7.4 +/- 0.9%, P = 0.019) and diabetic subjects (AGEs: 10.5 +/- 0.7 to 14.2 +/- 1 units/ml, P = 0.020; PAI-1: 6.5 +/- 1 to 10 +/- 2 ng/ml, P = 0.030; and FMD: 5.4 +/- 0.4 to 4.0 +/- 0.3%, P = 0.032). Serum glucose and VCAM-1 levels remained unchanged. CONCLUSIONS: Significant increases in serum AGEs can occur together with altered clinical measures of endothelial function in diabetic and nondiabetic subjects after a single modest AGE-rich beverage. Thus, repeated or chronic exposure to high AGE diets could over time lead to and/or accelerate vascular disease.