Objective To investigate the expression and clinical significance of serum C-C motif chemokine ligand 11 (CCL11) and phosphorylated neurofilament heavy chain (pNF-H) in diabetic peripheral neuropathy (DPN).
Methods A total of 174 patients with type 2 diabetes mellitus (T2DM) were enrolled as T2DM group, and 87 healthy volunteers who underwent physical examinations during the same period were selected as control group. The T2DM patients were divided into DPN group and non-DPN group based on the occurrence of DPN. According to the disease severityassessed by the Toronto Clinical Scoring System (TCSS), DPN patients were further classified into mild DPN group, moderate DPN group and severe DPN group. Enzyme-linked immunosorbent assay was used to measure the levels of CCL11 and pNF-H. Pearson correlation analysis was employed to examine the correlations of serum CCL11 and pNF-H levels with TCSS scores in DPN patients. Multivariate unconditional logistic regression analysis was conducted to screen for influencing factors of DPN in T2DM patients. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of serum CCL11 and pNF-H levels for the development of DPN in T2DM patients.
Results The serum levels of CCL11 and pNF-H in the T2DM group were significantly higher than those in the control group (P < 0.05). The incidence of DPN in the T2DM group was 47.13% (82/174). The age of the DPN group was significantly older, the disease course was significantly longer, and the levels of fasting blood glucose, HbA1c, CCL11 and pNF-H were significantly higher than those of the non-DPN group (P < 0.05). The serum levels of CCL11 and pNF-H increased sequentially from the mild DPN group to the moderate DPN group and then to the severe DPN group, with statistically significant differences (P < 0.05). Serum CCL11 and pNF-H levels in DPN patients were positively correlated with TCSS scores (r=0.661 and 0.619; P < 0.001). A prolonged disease duration, high glycated hemoglobin levels, high CCL11 levels and high pNF-H levels were independent risk factors for DPN in T2DM patients (P < 0.05). Thearea under the ROC curve for the combined prediction of DPN in T2DM patients by serum CCL11 and pNF-H levels was 0.861, which was greater than those for the individual indicators by serum CCL11 (0.751) and pNF-H (0.765) levels (P < 0.05). After 1, 000-time bootstrap internal validation through self-sampling, the C-index for the combined prediction was 0.861.
Conclusion Elevated serum levels of CCL11 and pNF-H are independently associated with the development of DPN in T2DM patients and increase with the worsening of DPN. The combination of these two markers has a high predictive value for DPN in T2DM patients.
DownLoad: