Plasma neurofilament light chain in type 2 diabetes: Associations with diabetic peripheral neuropathy, age, and renal function in a pilot cross-sectional study

Abstract

Background Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM). Neurofilament light chain (NfL) is a circulating marker of neuroaxonal injury, but its interpretation may be influenced by age and renal function. Objective To evaluate the association between plasma NfL concentrations and DPN in T2DM while accounting for age and renal function. Methods This pilot cross-sectional study included 41 patients with T2DM, of whom 20 had DPN diagnosed by a neurologist based on clinical and electrophysiological assessment and 21 had no DPN. Plasma NfL concentrations were measured using single-molecule array technology. Group differences and associations with clinical variables were assessed using non-parametric methods. Sequential linear regression models using natural log-transformed NfL evaluated the association of DPN status with NfL before and after adjustment for age and estimated glomerular filtration rate (eGFR). Results Plasma NfL concentrations were higher in patients with DPN than in those without DPN (median 12.96 vs 8.29 pg/mL, p = 0.035). In sequential regression analysis, DPN status was associated with higher ln-transformed NfL in the unadjusted model (B = 0.499, 95% CI 0.108–0.890; p = 0.014), but the association was attenuated after adjustment for age and eGFR (B = 0.241, 95% CI −0.040–0.522; p = 0.091). In the fully adjusted model, age and eGFR remained associated with ln(NfL), and the model explained 62.0% of its variance. Conclusions Plasma NfL concentrations were higher in patients with DPN in unadjusted analyses, but the association was attenuated after accounting for age and renal function. These exploratory findings highlight the importance of considering age and renal function when interpreting circulating NfL concentrations in T2DM and require confirmation in larger prospective cohorts.