Serum Neurofilament Light Chain in Diabetic Polyneuropathy: Associations with Neuropathy Burden, Balance Impairment, and Fear of Falling

Objective: To compare serum neurofilament light chain (NfL) concentrations between individuals with type 2 diabetes mellitus (T2DM) with and without diabetic polyneuropathy (DPN), and to examine associations with neuropathy burden, balance impairment, fear of falling, and fall history. Methods: This analytical cross-sectional study included 88 participants with T2DM (44 with DPN and 44 without DPN). Serum NfL was measured by enzyme-linked immunosorbent assay (ELISA); neuropathy burden was assessed with the Michigan Neuropathy Screening Instrument (MNSI), balance with the Berg Balance Scale (BBS), and fear of falling with the Falls Efficacy Scale-International (FES-I). Results: Serum NfL was higher in DPN than non-DPN participants [3.47 (2.68-4.77) vs. 2.47 (1.48-3.07) pg/mL; p < 0.001]. NfL correlated with MNSI-A (ρ = 0.562), MNSI-B (ρ = 0.550), FES-I (ρ = 0.431), falls (ρ = 0.344), and BBS (ρ = -0.450) (all p ≤ 0.001). In the comprehensively adjusted model, the NfL association was attenuated (adjusted odds ratio [aOR] = 1.352; 95% confidence interval [CI], 0.991-1.844; p = 0.057). NfL showed moderate discrimination (area under the receiver operating characteristic curve [AUC] = 0.716; 95% CI, 0.607-0.825); the internally derived Youden threshold was ≥2.823 pg/mL (sensitivity 72.7%, specificity 65.9%). Conclusions: NfL may be a complementary marker of DPN-related neuropathy and functional burden, but the adjusted association was attenuated and the study-specific threshold requires external validation. Study Registration: ClinicalTrials.gov identifier NCT07480330. The study was prospectively registered; the initial registry release occurred on 14 March 2026, before study initiation on 25 March 2026.