Corneal subepithelial nerve fibers in type 2 diabetes: potential biomarker of diabetic neuropathy.

Aim: To observe the changes in corneal subepithelial nerve fibers (CNFs) and Langerhans cells (LCs) in patients with type 2 diabetes using corneal laser confocal microscopy (CLCM).

Methods: A total of 60 patients (64 eyes), including 40 patients with type 2 diabetes (DM group) and 20 subjects without diabetes (control group) were included with CLCM. Neuron J plugin of Image J software were used for quantitative analysis of CNF length (CNFL), CNF density (CNFD), corneal nerve branch fiber density (CNBD), main branch length density, branch length density, corneal nerve fiber tortuosity (NT) score, and LCs density. An independent samples t-test to analyze the variability between the two groups was performed, and Pearson correlation analysis was used to analyze the relationships between CNF and multiple biochemical indicators in the DM group. The predictive power of CNF for type 2 diabetes was assessed using the receiver operating characteristic (ROC) curve.

Results: There were significant differences in the CNFL, CNFD, and main branch length density between two groups. The results of Pearson correlation analysis showed a significant negative correlation between CNFD and the duration of diabetes as well as triglyceride levels and total cholesterol, and a significant positive correlation between CNFD and serum albumin. In addition, the NT score showed a positive correlation and urea nitrogen, similar to the positive correlation observed between LC density and glycosylated hemoglobin (HbA1c) levels. CNFD showed the highest area under the curve (AUC of ROC) value, followed by main branch length density and CNFL. The AUC of the ROC curve under the logistic regression model also demonstrated good predictive values. The cut-off values of CNFD, CNFL, and main branch length density for diabetes showed 31.25, 18.85, and 12.56, respectively.

Conclusion: In patients with type 2 diabetes, there is a notable reduction in both CNFL and CNFD. These measurements can be influenced by various blood biochemical factors. However, the compromised nerve fibers can serve as valuable indicators for predicting the onset of type 2 diabetes and also as biomarkers for detecting diabetic neuropathy and its related complications.