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Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis

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Abstract

Tumor necrosis factor-α (TNF-α) is a cell signaling protein involved in systemic inflammation, and is also an important cytokine in the acute phase reaction. Several studies suggested a possible association between TNF-α and diabetic peripheral neuropathy (DPN) in type 2 diabetic patients, but no accurate conclusion was available. A systematic review and meta-analysis of observational studies was performed to comprehensively assess the association between serum TNF-α levels and DPN in type 2 diabetic patients. We searched Pubmed, Web of Science, Embase, and China Biology Medicine (CMB) databases for eligible studies. Study-specific data were combined using meta-analysis. Fourteen studies were finally included into the meta-analysis, which involved a total of 2650 participants. Meta-analysis showed that there were obviously increased serum TNF-α levels in DPN patients compared with type 2 diabetic patients without DPN (standard mean difference [SMD] = 1.203, 95 % CI 0.795–1.611, P < 0.001). There were also obviously increased levels of serum TNF-α in diabetic patients with DPN when compared with healthy controls (SMD = 2.364, 95 % CI 1.333–3.394, P < 0.001). In addition, there were increased serum TNF-α levels in painful DPN patients compared with painless DPN patients (SMD = 0.964, 95 % CI 0.237–1.690, P = 0.009). High level of serum TNF-α was significantly associated with increased risk of DPN in patients with type 2 diabetes (odds ratio [OR] = 2.594, 95 % CI 1.182–5.500, P = 0.017). Increased serum levels of TNF-α was not associated with increased risk of painful DPN in patients with type 2 diabetes (OR = 2.486, 95 % CI 0.672–9.193, P = 0.172). Sensitivity analysis showed that there was no obvious change in the pooled estimates when omitting single study by turns. Type 2 diabetic patients with peripheral neuropathy have obviously increased serum TNF-α levels than type 2 diabetic patients without peripheral neuropathy and healthy controls, and high level of serum TNF-α may be associated with increased risk of peripheral neuropathy independently. Further prospective cohort studies are needed to assess the association between TNF-α and DPN.

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Acknowledgments

We thank all the data provided by the authors of included studies.

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  1. Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China

    Ze-Peng Mu, Yan-Gang Wang, Cheng-Qian Li, Wen-Shan Lv, Bin Wang, Zhao-Hai Jing, Xue-Jia Song, Yu Lun, Ming-Yue Qiu & Xiao-Long Ma

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Mu, ZP., Wang, YG., Li, CQ. et al. Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis. Mol Neurobiol 54, 983–996 (2017). https://doi.org/10.1007/s12035-016-9702-z

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