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

Gong Xiaohua; Luo Dongdong; Niu Xiaoting; Chen Shuoping; Shen Feixia; Yang Huajun; Zhou Qi; Chen Zimiao

doi:10.3389/fnut.2021.612068

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

Front Nutr. 2021 Mar 10:8:612068. doi: 10.3389/fnut.2021.612068. eCollection 2021.

Authors

Gong Xiaohua¹, Luo Dongdong², Niu Xiaoting³, Chen Shuoping¹, Shen Feixia¹, Yang Huajun⁴, Zhou Qi¹, Chen Zimiao¹

Affiliations

¹ Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China.
³ Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Songqiao Hospital of Wanquan Town, Wenzhou, China.

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.

Keywords: IL-6; TNF–α; inflammatory cytokine; painful diabetic peripheral neuropathy; severe vitamin D deficiency; type 2 diabetes mellitus.