Abstract
To unravel associations between plasma xanthine oxidoreductase (XOR) and diabetic vascular complications, especially distal symmetric polyneuropathy (DSP), we investigated plasma XOR activities using a novel assay. Patients with type 2 diabetes mellitus (T2DM) with available nerve conduction study (NCS) data were analyzed. None were currently taking XOR inhibitors. XOR activity of fasting blood samples was assayed using a stable isotope-labeled substrate and LC-TQMS. JMP Clinical version 5.0. was used for analysis. We analyzed 54 patients. Mean age was 64.7 years, mean body mass index was 26.0 kg/m2, and mean glycated hemoglobin was 9.4%. The logarithmically transformed plasma XOR activity (ln-XOR) correlated positively with hypoxanthine, xanthine, visceral fatty area, and liver dysfunction but negatively with HDL cholesterol. ln-XOR correlated negatively with diabetes duration and maximum intima-media thickness. Stepwise multiple regression analysis revealed ln-XOR to be among selected explanatory factors for various NCS parameters. Receiver operating characteristic curves showed the discriminatory power of ln-XOR. Principal component analysis revealed a negative relationship of ln-XOR with F-waves as well as positive relationships of ln-XOR with hepatic steatosis and obesity-related disorders. Taken together, our results show plasma XOR activity to be among potential disease status predictors in T2DM patients. Plasma XOR activity measurements might reliably detect pre-symptomatic DSP.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disease that leads to various vascular complications involving multiple organs, reducing the lifespans of affected patients [1]
We investigated the associations of plasma xanthine oxidoreductase (XOR) activity in type 2 diabetes mellitus (T2DM) patients with individual parameters and diabetic vascular complications
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]
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disease that leads to various vascular complications involving multiple organs, reducing the lifespans of affected patients [1]. Diabetes prevalence rose in the second decade of the 21st century and continues to increase. In 2019, diabetes prevalence worldwide was estimated to be 463 million people [2], and 4.2 million people were estimated to have died from diabetes and its complications [3]. Prevention or early detection of T2DM and its complications is hugely important but occult and asymptomatic complications are difficult to detect. Distal symmetric polyneuropathy (DSP) especially often precedes other complications and can progress to become a life-threatening disorder [4]. The progression of DSP is very difficult to evaluate and employs routine outpatient examinations. Consensus definitions consistently recommend a combination of neuropathic symptoms and signs in addition to specific nerve conduction study (NCS) abnormalities as criteria for diagnosing
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