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

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.