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

Authors

Vera Fridman, University of Colorado Denver School of Medicine.
Stefan Sillau, University of Colorado Denver School of Medicine.
Alanna Ritchie, University of Colorado Denver School of Medicine.
Jacob Bockhorst, University of Colorado Denver School of Medicine.
Christina Coughlan, University of Colorado Denver School of Medicine.
Paula Araya, University of Colorado Denver School of Medicine.
Joaquin M. Espinosa, University of Colorado Denver School of Medicine.
Keith Smith, University of Colorado Denver School of Medicine.
Ethan M. Lange, University of Colorado Denver School of Medicine.
Leslie A. Lange, University of Colorado Denver School of Medicine.
Laure El Ghormli, The George Washington University Biostatistics Center.
Kimberly L. Drews, The George Washington University Biostatistics Center.
Philip Zeitler, University of Colorado Denver School of Medicine.
Jane E. Reusch, University of Colorado Denver School of Medicine.

Document Type

Journal Article

Publication Date

6-21-2023

Journal

Journal of the peripheral nervous system : JPNS

DOI

10.1111/jns.12575

Keywords

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

Abstract

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.

APA Citation

Fridman, Vera; Sillau, Stefan; Ritchie, Alanna; Bockhorst, Jacob; Coughlan, Christina; Araya, Paula; Espinosa, Joaquin M.; Smith, Keith; Lange, Ethan M.; Lange, Leslie A.; El Ghormli, Laure; Drews, Kimberly L.; Zeitler, Philip; and Reusch, Jane E., "Plasma Neurofilament Light Chain Concentrations are Elevated in Youth-onset Type 2 Diabetes and Associate with Neuropathy" (2023). GW Authored Works. Paper 2699.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2699

Department

Biostatistics and Bioinformatics