title: Toll-like receptor 4 and tumor necrosis factor-alpha as diagnostic biomarkers for diabetic peripheral neuropathy.
abstract: 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.
authors.affiliation: Department of Anesthesia, Songjiang Branch, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China. Electronic address: doctor.zhutao@gmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Nanjing Medical University.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Anesthesia, Songjiang Branch, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
authors.affiliation: Central Laboratory, Songjiang Branch, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Lou
authors.affiliation: Department of Endocrinology, Songjiang Branch, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003929:Diabetic Neuropathies / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D051197:Toll-Like Receptor 4 / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: Interleukin-6; Peripheral neuropathy; Toll-like receptor 4; Tumor necrosis factor-alpha; Type 2 diabetes mellitus