Serum Neurofilament Light Chain and Structural and Functional Nerve Fiber Loss in Painful and Painless Diabetic Polyneuropathy

Aims: To explore associations between the axonal protein neurofilament light chain (NfL) and severity of diabetic polyneuropathy (DPN) and pain. Methods: We performed cross-sectional analysis of a subset of the PiNS/DOLORisk cohort of people with DPN with and without neuropathic pain. Biobank samples were analyzed for serum NfL (s-NfL) using single molecule array. DPN was defined by Toronto criteria for probable or confirmed DPN. Painful DPN (PDPN) was evaluated according to IASP criteria. Measures of DPN severity included clinical DPN scales, quantitative sensory testing (QST) and intraepidermal nerve fiber density (IENFD). Results: Participants with confirmed (N = 172) or probable DPN (N = 29) were included. There was no s-NfL difference between participants with DPN (N = 79, 22.8 ng/L [IQR 17.4; 31.3]) and PDPN (N = 122, 22.2 ng/L [16.0; 34.4]). S-NfL was not associated with pain severity or DPN severity evaluated by clinical DPN scales. Higher s-NfL was associated with lower IENFD (13.6 % [95 % CI 3.1; 22.9], unit = 1 fiber/mm, N = 24) and more pronounced loss of nerve fiber function measured by QST (p-trend = 0.02). Conclusions: Higher s-NfL was associated with nerve fiber dysfunction and loss quantified by QST and IENFD, but not with pain or clinical DPN scales. S-NfL may reflect the severity of nerve fiber damage underlying DPN.