Lower serum 25-hydroxyvitamin D levels predict higher risk of DSPN in type 2 diabetes, and exhibit a non-linear association with the severity of DSPN

Background: Prior investigations have suggested a relationship in which vitamin D may be linked to distal symmetric polyneuropathy (DSPN), but these results are inconsistent. Moreover, few studies have examined the linear relationship between vitamin D levels and the severity of DSPN and no definitive clinical threshold has been identified. This study therefore investigated the connection between the level of serum 25-hydroxyvitamin D [25(OH)D] and the risk and severity of DSPN with special regard to the establishment of a clinically significant cutoff point to classify the risks. Methods: , and total 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). DSPN and its severity were assessed by using a standardized five-item neurological examination and the Michigan Neuropathy Screening Instrument (MNSI). Multivariable logistic regression was applied to examine the relationship between 25(OH)D and DSPN. Propensity score matching (PSM) was performed to minimize baseline imbalances and validate the robustness of the findings. Restricted cubic splines (RCS) were employed to construct a dose-response curve and identify a possible threshold. Results: concentrations presented no evident intergroup difference (P = 0.645). Quartile analysis demonstrated a significant downward trend in the risk of DSPN with increasing 25(OH)D levels (P for trend < 0.001). After controlling for potential confounders, 25(OH)D continued to exert an independent protective effect, and this conclusion remained valid even after propensity score matching. RCS analysis revealed that 25(OH)D and DSPN risk had a linear negative relationship, and a nonlinear relationship was observed with the severity of neuropathy with an turning point at about 26.1 ng/mL. Additional examination revealed that the severity of DSPN increased significantly as the level of 25(OH)D dropped below this point. Conclusion: 25(OH)D was inversely associated with the risk of DSPN, and exhibited a nonlinear relationship with neuropathy severity. Notably, when 25(OH)D levels dropped below 26.1 ng/mL, the severity of DSPN appeared to accelerate markedly. Therefore, 25(OH)D levels have the potential to be a readily accessible and clinically useful indicator to screen and categorize DSPN risk in the early stages.