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

Abstract

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-α (TNF-α), and interferon-γ (IFN-γ) 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-α (P < 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 (r = −0.56, P < 0.01) and TNF-α (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-α levels.

Title: Understanding a Low Vitamin D State in the Context of COVID-19

“…Severe Covid is associated with angiotensin-converting enzyme 2 (ACE2) suppression and increased coagulability (Ragab et al, 2016;Rhodes et al, 2021); immunological and biochemical signatures which can be attenuated by vitamin D. Furthermore, there is a profound dysregulation of both the innate and adaptive immune systems with advancing age, with some functions down-regulated, and others up-regulated or even enhanced which contribute to the severity of responses to SARS-CoV-2 in older adults. (Manion et al, 2017;Kadijani et al, 2021;Rasmussen et al, 2021;Rezaei et al, 2021;Xiaohua et al, 2021).…”

Investigating the Association between Diabetic Neuropathy and Vitamin D in Emirati Patients with Type 2 Diabetes Mellitus

“…It was concluded that severe vitamin D deficiency was an independent risk factor for painful DPN. They also concluded that severe vitamin D deficiency may play a role in the painful DPN pathogenesis through elevated IL-6 and TNF-α level [29].…”

Effect of obesity on the associations of 25-hydroxyvitamin D with prevalent and incident distal sensorimotor polyneuropathy: population-based KORA F4/FF4 study

“…Second, vitamin D has anti-inflammatory and immunomodulatory actions, which might be reduced in low 25(OH)D status contributing to the pathogenesis of DSPN. Notably, a severe vitamin D deficiency has been found associated with increased expression of inflammatory cytokines [ 52 ], particularly interleukin-6 and tumor necrosis factor-α, both previously reported to increase the risk of DSPN [ 53 ].…”