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

Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha 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-alpha 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-alpha 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-alpha 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-alpha 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-alpha 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-alpha levels than type 2 diabetic patients without peripheral neuropathy and healthy controls, and high level of serum TNF-alpha may be associated with increased risk of peripheral neuropathy independently. Further prospective cohort studies are needed to assess the association between TNF-alpha and DPN.