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.

Chronic Nerve Compression Accelerates the Progression of Diabetic Peripheral Neuropathy in a Rat Model: A Study of Gene Expression Profiling

“…several studies have suggested the strong association between TNF and DPN progression. 19,20 Our findings on the one hand reconfirmed those metabolic abnormalities in the diabetic nerve, and on the other hand found that those metabolic abnormalities were further enhanced by chronic mechanical compression during the progression of DPN.…”

Amyloid Proteins and Peripheral Neuropathy

“…In addition, accumulation of hIAPP in the brains of transgenic rats and injection of aggregated hIAPP in mice are linked to neuroinflammation and neurologic deficits [ 159 ]. Finally, serum TNF levels are higher in T2DM patients with peripheral neuropathy as compared to T2DM patients without peripheral neuropathy, providing further support for an inflammatory component in development of peripheral neuropathy in T2DM [ 253 ].…”

Involvement of microRNA-146a in diabetic peripheral neuropathy through the regulation of inflammation

“…Molecular studies have revealed that abnormal expression of inflammatory cytokines in the microvasculature around peripheral nerves is found in DPN patients and relevant animal models. 7 , 8 The precise process by which inflammatory damage to peripheral nerves occurs requires further clarification.…”