title: Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis.
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.
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Ze-Peng
authors.initials: ZP
authors.lastname: Mu
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China. mzpmzpp@hotmail.com.
authors.forename: Yan-Gang
authors.initials: YG
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Cheng-Qian
authors.initials: CQ
authors.lastname: Li
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Lv
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Zhao-Hai
authors.initials: ZH
authors.lastname: Jing
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Xue-Jia
authors.initials: XJ
authors.lastname: Song
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lun
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Ming-Yue
authors.initials: MY
authors.lastname: Qiu
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Ma
mesh_terms: D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D003929:Diabetic Neuropathies / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha
keywords: Diabetic peripheral neuropathy; Meta-analysis; Tumor necrosis factor-α