Short communicationToll-like receptor 4 and tumor necrosis factor-alpha as diagnostic biomarkers for diabetic peripheral neuropathy

•Higher BMI, HbA1c, TLR4, TNF-α, and IL-6 were related with diabetic neuropathy.•TLR4 and TNF-α had great potential advantages to predict neuropathic progression.•The OR of DPN were 5.27 (95% CI: 1.02-26.40) in T2DM patients with high TLR4.•The OR of DPN were 12.67 (95% CI: 2.35-68.22) in T2DM patients with high TNF-α.

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes, but currently no protein biomarkers have been introduced into clinical diagnosis, especially among early-stage diabetic patients. Our previous study in animal model showed Toll-like receptor (TLR) 4 and its downstream signaling molecules were associated with DPN. To assess the diagnostic values of TLR4, TNF-α, and IL-6 as biomarkers, here we detected their expressions in peripheral blood from normal controls, type 2 diabetic and DPN subjects. Both TLR4 mRNA and protein expressions increased significantly in DPN compare with both diabetic and control subjects. The protein levels of TNF-α and IL-6 were also raised significantly and correlated with TLR4 expression. Receiver operating characteristics (ROC) analysis suggested TLR4 and TNF-α had great potential advantages to predict the progression of neuropathy, the risks of DPN were increased in subjects with higher TLR4 (odds ratio: 5.27; 95% CI: 1.02-26.40) and TNF-α (odds ratio: 12.67; 95% CI: 2.35-68.22). These findings demonstrated TLR4 and TNF-α could be potential sensitive diagnostic biomarkers for DPN in both general population and type 2 diabetic subjects.