Positive association of serum levels of advanced glycation end products with thrombogenic markers in humans.

Advanced glycation end products (AGEs) are elevated in diabetes. We have demonstrated that AGEs trigger thrombogenic responses in cultured cells. We investigated here whether serum AGE levels were positively correlated with thrombogenic markers in humans. Data for fasting serum AGE levels of 186 nondiabetic subjects were obtained from a general population in Japan. We measured body mass index, blood pressure, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, glycosylated hemoglobin A(1c), insulin, creatinine, uric acid, high-sensitive C-reactive protein, plasminogen activator inhibitor 1 (PAI-1), and fibrinogen. Uni- and multivariate analyses were applied for the determinants of serum AGE levels. The average AGE levels were 4.11 +/- 0.74 U/mL in males and 4.10 +/- 0.93 U/mL in females. In the univariate analysis, PAI-1 (P < .05) and fibrinogen (P < .05) were significantly associated with AGE levels. After performing multivariate analyses, PAI-1 (P < .05) and fibrinogen (P < .05) still remained significant independently. In conclusion, the present study is the first demonstration that PAI-1 and fibrinogen levels were positively associated with serum AGE levels. Advanced glycation end products may be associated with thrombogenesis in humans.