Longitudinal Change in Serum Neurofilament Light Chain in Type 2 Diabetes and Early Diabetic Polyneuropathy: ADDITION-Denmark

Objective To investigate the longitudinal development of neurofilament light chain (NfL) levels in type 2 diabetes with and without diabetic polyneuropathy (+/-DPN) and to explore the predictive potential of NfL as a biomarker for DPN. Research Design and Methods We performed retrospective longitudinal case-control analysis of data from 178 participants of the ADDITION-Denmark cohort of people with screen-detected type 2 diabetes. Biobank samples acquired at the ADDITION-Denmark 5- and 10-year follow-up were analyzed for serum NfL (s-NfL) using single-molecule array and the results were compared to established reference material to obtain NfL z-scores. DPN was diagnosed according to Toronto criteria for confirmed DPN at the 10-year follow-up. Results S-NfL increased over time in +DPN (N=39) and -DPN participants (N=139) at levels above normal age-induced s-NfL increase. Longitudinal s-NfL change was greater in +DPN than in -DPN participants (17.4% [95% CI 4.3; 32.2] or 0.31 SD [95% CI 0.03; 0.60] higher s-NfL or NfL z-score increase in +DPN compared to -DPN). S-NfL at 5-year follow-up was positively associated to nerve conduction studies at 10-year follow-up (p=0.02 to <0.001), but not to DPN risk. AUC’s for s-NfL were not inferior to AUC’s for the Michigan Neuropathy Screening Instrument questionnaire score or vibration detection thresholds. Higher yearly s-NfL increase was associated to higher DPN risk (OR 1.36 [95% CI 1.08; 1.71] per 1 ng/L/year). Conclusions Our findings suggest that preceding s-NfL trajectories differ slightly between those with and without DPN and imply a possible biomarker value of s-NfL trajectories in DPN.