Severe Vitamin D Deficiency Is Associated With Increased Expression of Inflammatory Cytokines in Painful Diabetic Peripheral Neuropathy

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. A total of 483 patients were divided into three groups, i.e., diabetes without DPN (no-DPN, = 86), diabetes with painless DPN (painless DPN, = 176) and diabetes with painful DPN (painful DPN, = 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-α (TNF-α), and interferon-γ (IFN-γ) were also measured. 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, < 0.01). Cases in the painful DPN group had significantly higher concentrations of IL-6 ( < 0.01) and TNF-α ( < 0.01) than those in the two other groups. The multivariate logistic analysis showed that severe vitamin D deficiency, IL-6, and TNF-α were independent risks for painful DPN after adjusting for confounding factors. Furthermore, the vitamin D status had significantly negative correlations with IL-6 ( = -0.56, < 0.01) and TNF-α ( = -0.47, < 0.01) levels. 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-α levels.