Objective: Vitamin D deficiency is associated with patients with diabetic peripheral neuropathy (DPN), and low levels of vitamin D are common in patients with depression. Depression is common in DPN patients and the definite pathogenesis remains unclear. This study aimed to determine vitamin D deficiency in the onset of depression in DPN and evaluate the effect of vitamin D supplementation on depression.
Methods: A total of 192 patients with DPN were enrolled in this study. Clinical and laboratory information was collected. Chemiluminescent immunoassay was used to measure the level of 25(OH)D. Enzyme-linked immunosorbent assay was employed to measure the concentrations of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-17A. Subjects with low 25(OH)D received 5000IU vitamin D daily for 12 weeks. Depression scores and levels of 25(OH)D, IL-1β, TNF-α, and IL-17A were re-evaluated after supplementation.
Results: The incidence of vitamin D deficiency and depression was high in DPN patients. Compared with vitamin D sufficient participants, Hamilton Depression Rating Scale (HAMD) scores and the levels of inflammatory markers IL-1β, TNF-α, and IL-17A were significantly higher in insufficient group (all p< 0.05). HAMD score, IL-1β, TNF-α, and IL-17A were negatively correlated with 25(OH)D (all p< 0.05). A linear relationship existed among IL-1β, TNF-α, IL-17A, and 25(OH)D (p< 0.05). HAMD scores, IL-1β, TNF-α, and IL-17A were all reduced significantly after supplementation of vitamin D (p< 0.05). Binary logistic analysis revealed that vitamin D insufficiency was an independent risk factor for depression in patients with DPN. Receiver operating characteristic (ROC) curve analysis showed a high sensitivity (87.20%) of 25(OH)D in discriminating DPN patients with depression.
Conclusion: Vitamin D deficiency participated in occurrence of depression in DPN patients and could be mediated, at least in part, by upregulation of pro-inflammatory cytokines. Vitamin D supplementation may be effective in improving depressive symptoms in DPN patients.

Keywords: vitamin D, depression, diabetic peripheral neuropathy, interleukin-1 beta, tumor necrosis factor-alpha, interleukin-17A