Neurofilament light chain and nerve growth factor as biomarkers of axonal injury and neurotrophic dysfunction in diabetic neuropathy

Introduction and aim. Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and is often diagnosed at an advanced stage when nerve damage becomes irreversible. Neurofilament light chain (NfL), a neuroaxonal injury marker, and nerve growth factor (NGF), a neurotrophin, are potential biomarkers for evaluating axonal damage and neurotrophic support in DPN. This study aimed to evaluate the efficacy of serum NfL and NGF as concurrent biomarkers of axonal injury and impaired neurotrophic support in a single cohort of patients with DPN, exploring their relationship with clinical and electrophysiological parameters. Material and methods. A case-control study was conducted, including 30 patients with type 2 diabetes mellitus (T2DM) and DPN, 30 patients with T2DM without neuropathy (diabetic controls), and 60 healthy control subjects. Serum NfL and NGF concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The primary outcome was the receiver operating characteristic (ROC) performance of serum NfL for discriminating patients with DPN from healthy controls. Results. Serum NfL levels were significantly elevated in patients with DPN (13.9±1.20 ng/mL) compared with diabetic controls (9.83±2.08 ng/mL) and healthy controls (5.60±2.53 ng/mL) (p<0.0001). Conversely, NGF levels were significantly lower in both diabetic groups than in healthy controls (p<0.0001). In this case-control sample, ROC analysis showed that serum NfL discriminated against DPN from healthy controls with an area under the curve (AUC) of 0.994 (sensitivity 96.6%, specificity 100.0%), though this exceptionally high performance reflects discrimination against healthy individuals rather than diabetic controls. Conclusion. Serum NfL and NGF represent promising candidate biomarkers of axonal injury and impaired neurotrophic support in DPN, respectively, and were correlated with glycemic control and disease duration in this cohort. However, given the small, single-center, case-control design, further validation in larger, longitudinal, and duration-matched cohorts is required before clinical implementation can be considered.