Plasma Neurofilament Light Chain Concentrations are Elevated in Youth-onset Type 2 Diabetes and Associate with Neuropathy

Document Type

Journal Article

Publication Date



Journal of the peripheral nervous system : JPNS




biomarkers; cardiac autonomic neuropathy; diabetic neuropathy; type 2 diabetes; youth-onset diabetes


Background and Aims The lack of easily measurable biomarkers remains a challenge in executing clinical trials for diabetic neuropathy (DN). Plasma Neurofilament light chain (NFL) concentration is a promising biomarker in immune-mediated neuropathies. Longitudinal studies evaluating NFL in DN have not been performed. METHODS: A nested case-control study was performed in participants with youth-onset type 2 diabetes enrolled in the prospective Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Plasma NFL concentrations were measured at 4-year intervals from 2008-2020 in 50 participants who developed DN and 50 participants with type 2 diabetes who did not develop DN. RESULTS: NFL concentrations were similar in the DN and no DN groups at first assessment. Concentrations were higher in DN participants at all subsequent assessment periods (all p<0.01). NFL concentrations increased over time in both groups, with higher degrees of change in DN participants (interaction p=0.045). A doubling of the NFL value at Assessment 2 in those without DN increased the odds of ultimate DN outcome by an estimated ratio of 2.86 (95% CI: (1.30, 6.33), p=0.0046). At the final study visit, positive Spearman correlations (controlled for age, sex, diabetes duration, and BMI) were observed between NFL and HbA1c (0.48, p<0.0001), total cholesterol (0.25, p=0.018), and LDL (0.30, p=0.0037). Negative correlations were observed with measures of heart rate variability (-0.42 to -0.46, p=<0.0001). Interpretation The findings NFL concentrations are elevated in individuals with youth-onset type 2 diabetes, and increase more rapidly in those who develop DN, suggest NFL could be a valuable biomarker for DN. This article is protected by copyright. All rights reserved.


Biostatistics and Bioinformatics