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Nutr."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> 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.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A total of 483 patients were divided into three groups, i.e., diabetes without DPN (no-DPN, <jats:italic>n<\/jats:italic> = 86), diabetes with painless DPN (painless DPN, <jats:italic>n<\/jats:italic> = 176) and diabetes with painful DPN (painful DPN, <jats:italic>n<\/jats:italic> = 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-\u03b1 (TNF-\u03b1), and interferon-\u03b3 (IFN-\u03b3) were also measured.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The prevalence of severe vitamin D deficiency (&amp;lt;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, <jats:italic>P<\/jats:italic> &amp;lt; 0.01). Cases in the painful DPN group had significantly higher concentrations of IL-6 (<jats:italic>P<\/jats:italic> &amp;lt; 0.01) and TNF-\u03b1 (<jats:italic>P<\/jats:italic> &amp;lt; 0.01) than those in the two other groups. The multivariate logistic analysis showed that severe vitamin D deficiency, IL-6, and TNF-\u03b1 were independent risks for painful DPN after adjusting for confounding factors. Furthermore, the vitamin D status had significantly negative correlations with IL-6 (<jats:italic>r<\/jats:italic> = \u22120.56, <jats:italic>P<\/jats:italic> &amp;lt; 0.01) and TNF-\u03b1 (<jats:italic>r<\/jats:italic> = \u22120.47, <jats:italic>P<\/jats:italic> &amp;lt; 0.01) levels.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> 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-\u03b1 levels.<\/jats:p>","DOI":"10.3389\/fnut.2021.612068","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T05:02:41Z","timestamp":1615352561000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Severe Vitamin D Deficiency Is Associated With Increased Expression of Inflammatory Cytokines in Painful Diabetic Peripheral 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