Association between Serum Uric Acid and Large-Nerve Fiber Dysfunction in Type 2 Diabetes: A Cross-Sectional Study
Introduction Large-nerve fiber dysfunction, as assessed by vibration perception threshold (VPT), is a significant predictor of risks such as ulceration, amputation, and mortality in diabetes. Serum uric acid (UA), a byproduct of purine synthesis, has been closely linked with various metabolic disorders, particularly diabetes. This study aimed to explore the clinical relevance of UA to large-nerve fiber dysfunction among patients with type 2 diabetes (T2D).
Methods The study utilized medical records of consecutive T2D patients admitted to Beijing Friendship Hospital Pinggu Campus between May 2014 and December 2016. Data from 824 eligible patients were extracted using a structured form. An abnormal VPT was defined as a value ≥15 in either foot. Clinical characteristics were compared between patients with abnormal VPT and those with normal VPT (VPT value <15 in both feet) in the overall population and gender subgroups. Logistic regression analysis was used to explore the association of abnormal VPT with UA level, and one-way analysis of variance was employed to compare VPT values across four UA quartiles.
Results UA levels were significantly lower in T2D patients with abnormal VPT than in those with normal VPT (294.5 ± 84.0 vs. 314.9 ± 92.8 mmol/L, P < 0.01), particularly among male patients (311.7 ± 85.2 vs. 336.9 ± 89.6 mmol/L, P 420 mmol/L; females >360 mmol/L) was associated with a reduced risk of abnormal VPT (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.39–0.91; P < 0.05). This association was robust in male patients (OR, 0.43; 95% CI, 0.24–0.76; P < 0.01) but not in female patients (OR, 0.92; 95% CI, 0.47–1.82; P = 0.816), even after adjustment for confounding factors. In the younger male subgroup (age <65 years), VPT values decreased as the UA level increased (P for trend = 0.002), but this trend was not significant in the older male subgroup (age ≥65 years; P for trend = 0.400).
Discussion The study found that lower serum UA levels were significantly associated with an increased risk of large-nerve fiber dysfunction in male patients with T2D, but not in female patients. Additionally, in the younger subgroup of male patients (<65 years), lower levels of UA correlated with higher VPT values. These findings suggest that UA may play a protective role against large-nerve fiber dysfunction in male T2D patients, particularly in younger individuals.
The protective role of UA has been demonstrated in various studies. UA is known for its antioxidant and anti-inflammatory properties, which may contribute to its protective effects. The reduction in UA levels reduces oxidant and peroxynitrite scavenging capacity, potentially leading to increased oxidative stress and nerve damage. This study supports the hypothesis that UA could be a significant factor in mitigating the progression of diabetic peripheral neuropathy (DPN), especially in male patients.
Traditional risk factors for abnormal VPT, such as age, diabetes duration, and hypertension, were also observed in this study. Patients with abnormal VPT tended to be older and had a longer duration of diabetes, which aligns with previous findings. The presence of comorbidities like hypertension further corroborates the relationship between these risk factors and the occurrence of large-nerve fiber dysfunction.
Limitations The study has several limitations. First, the lack of information on nerve conduction and/or tissue biopsies means that formal measurements of neural dysfunction were not available. Although VPT is a non-invasive test for detecting loss of protective sensation, it is not as comprehensive as other diagnostic methods. Second, UA levels were tested within the nearest 3 days before or after hospitalization rather than at a fixed time with a restricted low-purine diet, which might have influenced the results. Third, the study relied on electronic medical records, so information on lifestyle factors like smoking, drinking, diet, and exercise was not available. However, the study attempted to adjust for all collected confounders. Fourth, being a single-centered study, the results may not be generalizable to other populations. Despite these limitations, the study involved a large pool of T2D patients, providing valuable insights into the association between UA levels and large-nerve fiber dysfunction.
Conclusion In conclusion, lower serum levels of UA were significantly associated with an increased risk of large-nerve fiber dysfunction in male patients with T2D, but not in female patients. Additionally, in the younger subgroup of male patients (<65 years), lower levels of UA correlated with higher VPT values. These findings suggest that UA may play a protective role against large-nerve fiber dysfunction in male T2D patients, particularly in younger individuals. Further research is warranted to confirm these findings and explore the underlying mechanisms.
doi.org/10.1097/CM9.0000000000000223
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