Serum neurofilament light chain in diabetic patients with and without polyneuropathy: a systematic review and meta-analysis

Background Diabetes mellitus is a prevalent global health issue, affecting approximately 14% of individuals as latest reported. Among its complications, diabetic peripheral polyneuropathy (DPN) is a major cause of morbidity, impacting up to half of patients with long-standing diabetes. Given the limitations of current diagnostic methods, there is an urgent need for reliable biomarkers for early detection and management of DPN. Neurofilament light chain (NFL), a structural neuronal protein, has been proposed as a potential biomarker due to its release into the blood and cerebrospinal fluid following axonal damage. This systematic review and meta-analysis aim to evaluate serum NFL levels in diabetic patients with and without polyneuropathy compared to healthy controls. Methods A systematic search was conducted in four databases: Web of Science, PubMed, Scopus, and Embase. Studies were included if they measured serum NFL levels in diabetic patients, with or without polyneuropathy, and compared these levels to healthy controls. The Newcastle-Ottawa Scale (NOS) and JBI Critical Appraisal tools were used for quality assessment. We performed a meta-analysis using Review Manager 5.4 version, and assessed heterogeneity through chi-square tests and I² statistics. Results Eight studies (n = 2980 participants, including 950 diabetic patients and 2030 healthy controls) met the inclusion criteria. Three studies specifically evaluated serum NFL levels in diabetic patients with polyneuropathy. Meta-analysis revealed significantly elevated serum NFL levels in diabetic patients compared to healthy controls. Similarly, diabetic patients with polyneuropathy exhibited higher NFL levels than healthy controls. However, due to the limited number of studies comparing diabetic patients with and without neuropathy, a definitive conclusion on NFL's specificity to DPN remains uncertain. Heterogeneity analysis showed a moderate to high variation among studies, with a slight reduction after sensitivity analysis. Conclusion This study highlights elevated serum NFL levels in diabetic patients, irrespective of polyneuropathy status, suggesting that diabetes itself may contribute to increased NFL release. However, due to limited studies assessing NFL in DPN, further research is required to clarify its role as a specific biomarker for DPN.