Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment

Abstract

Aims/Introduction Xanthine oxidoreductase (XOR) is an enzyme that catalyzes hypoxanthine and xanthine to xanthine and uric acid, respectively. Plasma XOR activity has recently been measured in humans. However, limited information is known about plasma XOR activity in patients with type 2 diabetes mellitus, and its changes after short‐term glycemic control treatment. Materials and Methods We enrolled 28 Japanese patients (10 men/18 women) with type 2 diabetes mellitus who were hospitalized to undergo medical treatment for diabetes. Plasma XOR activity, quantified using triple quadrupole mass spectrometry and liquid chromatography, and other clinical parameters were examined at admission and 2 weeks after treatment during hospitalization. Changes in plasma XOR activity after treatment during hospitalization and associated clinical parameters were assessed. Results At the time of admission, the median plasma XOR activity was 83.1 pmol/h/mL, with a wide range of 14.4–1150 pmol/h/mL. Multiple regression analysis identified serum aspartate transaminase and alanine transaminase levels as significant and independent factors correlating with the baseline plasma XOR. Two weeks of treatment during hospitalization was associated with a significant decrease in plasma XOR activity. Changes in serum aspartate transaminase were also the only significant and independent factor correlating with changes in plasma XOR activity. Conclusions A close relationship was observed between plasma XOR activity and liver transaminases in patients with type 2 diabetes mellitus, cross‐sectionally, and also across treatment during hospitalization.

Association between Plasma Xanthine Oxidoreductase Activity and the Renal Function in a General Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study

“…It has been reported that XOR activity was positively correlated with HbA1c in patients with diabetes. Shortterm carbohydrate-restricted treatment (2 weeks of inpatient treatment) reduced plasma XOR activity, suggesting that diabetes may play an important role in regulating XOR activity [32]. Indeed, the present study showed that the HbA1c levels were highest in patients with the highest XOR quartile, which is in line with the report's findings mentioned above (Table 2) [32].…”

Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease

“…In addition, elevated plasma XOR activity has been reported to be associated with increased CVD events in heart failure patients with preserved ejection function [42] and higher mortality in cardiovascular intensive care patients [43], as well as an independent predictor of CVD events in CKD and hemodialysis patients [10]. Interestingly, Kawachi et al [44] demonstrated that short-term glycemic control treatment (2 weeks hospitalization) decreased plasma XOR activity in patients with type 2 DM. Together, findings showing an association between glycemic control and plasma XOR activity in patients with type 1 diabetes [36], patients under hemodialysis in our previous study [18], and pre-dialysis CKD patients in the present study suggest the importance of glycemic control in regard to decreased XOR, possibly leading to a decrease in CVD events.…”

Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes

“…Recently, relationships between various clinical features and the level of plasma XOR activity measured by the procedure used in our present study have been reported. For example, plasma XOR activity is related to obesity and habitual smoking in the general population [35], vascular endothelial dysfunction assessed by flow-mediated dilation in patients with type 1 diabetes [36], liver dysfunction in T2DM patients [37], the prevalence rate of coronary artery spasm [38], and adverse clinical outcomes in patients with heart failure but with a preserved ejection fraction [39], as well as the requirement for cardiovascular intensive care [40]. Previous studies demonstrated that XOR activity is upregulated in patients with diabetic vascular complications [41][42][43][44].…”