Severe Vitamin D Deficiency Is Associated With Increased Expression Of Inflammatory Cytokines In Painful Diabetic Peripheral Neuropathy

Background: The exact pathogenic mechanism of the painful diabetic peripheral neuropathy (DPN) is poorly understood. Our study aimed to evaluate the association amongst vitamin D status, inflammatory cytokines, and painful DPN.Methods: A total of 483 patients were divided into three groups, i.e., diabetes without DPN (no-DPN, n = 86), diabetes with painless DPN (painless DPN, n = 176) and diabetes with painful DPN (painful DPN, n = 221) groups. Basic information and laboratory results were collected. The concentrations of vitamin D (25-hydroxyvitamin D), high-sensitivity C-reactive protein, interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were also measured.Results: The prevalence of severe vitamin D deficiency (<10 ng/mL) was more common in the painful DPN group than in the painless DPN and no-DPN groups (25.8,12.5, and 8.1%, respectively, P < 0.01). Cases in the painful DPN group had significantly higher concentrations of IL-6 (P < 0.01) and TNF-alpha (P < 0.01) than those in the two other groups. The multivariate logistic analysis showed that severe vitamin D deficiency, IL-6, and TNF-alpha were independent risks for painful DPN after adjusting for confounding factors. Furthermore, the vitamin D status had significantly negative correlations with IL-6 (r = -0.56, P < 0.01) and TNF-alpha (r = -0.47, P < 0.01) levels.Conclusion: Severe vitamin D deficiency was an independent risk factor for the painful DPN. Severe vitamin D deficiency status may play a role in the painful DPN pathogenesis through elevated IL-6 and TNF-alpha levels.