Advanced Glycation End Products in Nondiabetic Patients With Coronary Artery Disease

Advanced Glycation End Products in Nondiabetic Patients With Coronary Artery Disease Masao Kanauchi , MD , Nobuhiro Tsujimoto , MD and Toshio Hashimoto , MD First Department of Internal Medicine, Nara Medical University, Nara, Japan Abstract OBJECTIVE —To investigate whether advanced glycation end products (AGEs) participate in the development of coronary artery disease (CAD) in nondiabetic and diabetic subjects. RESEARCH DESIGN AND METHODS —Serum concentrations of AGEs were measured using a newly established enzyme-linked immunosorbent assay in 48 nondiabetic patients (normal glucose tolerance, n = 20; impaired glucose tolerance, n = 28) who received coronary angiography for the study of chest pain or suspected CAD. Insulin sensitivity was examined by the euglycemic-hyperinsulinemic glucose clamp technique and was estimated as the mean glucose infusion rate during the last 30 min of clamp time ( M value). RESULTS —Patients were classified into four groups based on the number of significantly stenosed vessels, defined as 0-, 1-, 2-, or 3-vessel disease. Serum concentrations of AGEs were significantly higher in nondiabetic subjects with CAD than in control subjects (2.42 ± 0.65 vs. 1.96 ± 0.40 mU/ml, P < 0.01) and significantly correlated with the number of significantly stenosed vessels ( r = 0.678, P < 0.001). M values significantly inversely correlated with serum concentrations of AGEs ( r = −0.490, P < 0.05). In multiple regression analysis, with the number of significantly stenosed vessels as the dependent variable, serum concentrations of AGEs, 2-h plasma glucose, and areas under the plasma glucose response curve were independently associated. CONCLUSIONS —This pilot study indicates the relation between AGEs and the severity of CAD in nondiabetic patients. The measurement of serum AGE concentrations may be predictive of vascular damage. AGE, advanced glycation end product AUCglu, area under the plasma glucose response curve CAD, coronary artery disease CML, carboxymethyllysine ECG, electrocardiogram IGT, impaired glucose tolerance NGT, normal glucose tolerance Footnotes Address correspondence and reprint requests to Dr. Masao Kanauchi, First Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan. Received for publication 22 January 2001 and accepted in revised form 16 May 2001. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.