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Single Oral Challenge by Advanced Glycation End Products Acutely Impairs Endothelial Function in Diabetic and Nondiabetic Subjects

¹ Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York
² Heart and Diabetes Center NRW, Ruhr-University of Bochum, Bad Oeynhausen, Germany
³ German Diabetes Center, Heinrich-Heine-University, Duesseldorf, Germany
⁴ Division of Diabetes and Aging Research, The Brookdale Department of Geriatrics, Mount Sinai School of Medicine, New York, New York

Address correspondence and reprint requests to Jaime Uribarri, MD, Mount Sinai School of Medicine, One Gustave Levy Pl., New York, NY 10029. E-mail: jaime.uribarri{at}mssm.edu

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 (1.8 x 10⁶ 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.

Abbreviations: AGE, advanced glycation end product • CML, N-(carboxymethyl)lysine • CVD, cardiovascular disease • FMD, flow-mediated dilation • PAI-1, plasminogen activator inhibitor 1 • sAGE, serum AGE • VCAM-1, vascular cell adhesion molecule 1

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