Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes: a cross-sectional study in a hospital setting

Abstract

Background Xanthine oxidoreductase (XOR) is a rate-limiting enzyme that catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species (ROS) and causes endothelial dysfunction. To explore the association of XOR and its substrate with the vascular complications in patients with type 2 diabetes mellitus (hereafter simply, diabetes), we measured the plasma XOR activity and plasma levels of xanthine and hypoxanthine in patients with type 2 diabetes. Materials and Methods Plasma XOR activity and the plasma levels of xanthine and hypoxanthine were measured, and their associations with the clinical parameters and vascular complications were investigated in 94 Japanese inpatients with type 2 diabetes. Results Both the plasma XOR activity and plasma xanthine levels were correlated with the serum uric acid level. The plasma XOR activity was correlated with the plasma xanthine level, but not the plasma hypoxanthine level. The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index (BMI), serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the serum high density lipoprotein cholesterol levels (HDL-C). The plasma XOR activity also showed a positive correlation with the serum triglyceride (TG) levels. Plasma xanthine was positively correlated with the Fib4-index. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. In addition, a negative correlation was observed between the plasma XOR activity and the duration of diabetes, and positive correlations were observed between the plasma XOR activity and the coefficient of variation of the R-R interval (CVR-R) and sensory nerve conduction velocity (SCV). Furthermore, the plasma XOR activity was found to be significantly decreased in patients with coronary artery disease. Conclusions The plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in patients with type 2 diabetes