{"doi":"10.1111/jns.12575","title":"Plasma neurofilament light chain concentrations are elevated in youth‐onset type 2 diabetes and associated with neuropathy","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 on 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 to 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 the first assessment. Concentrations were higher in DN participants at all subsequent assessment periods (all p < .01). NFL concentrations increased over time in both groups, with higher degrees of change in DN participants (interaction p = .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 = .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 < .0001), total cholesterol (0.25, p = .018), and low-density lipoprotein (LDL (0.30, p = .0037)). Negative correlations were observed with measures of heart rate variability (-0.42 to -0.46, p = <.0001). INTERPRETATION: The findings that NFL concentrations are elevated in individuals with youth-onset type 2 diabetes, and increase more rapidly in those who develop DN, suggest that NFL could be a valuable biomarker for DN.","journal":"Journal of the Peripheral Nervous System","year":2023,"id":357884,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8376,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":350081,"name":"Stefan Sillau","orcid":"0000-0002-8691-3139","position":1,"is_corresponding":false},{"id":482329,"name":"Alanna Ritchie","orcid":"0009-0007-6970-7687","position":2,"is_corresponding":false},{"id":1108019,"name":"Jacob Bockhorst","orcid":null,"position":3,"is_corresponding":false},{"id":417379,"name":"Christina Coughlan","orcid":"0000-0002-7229-7056","position":4,"is_corresponding":false},{"id":313593,"name":"Paula Araya","orcid":"0000-0002-0340-5359","position":5,"is_corresponding":false},{"id":313603,"name":"Joaquı́n M. Espinosa","orcid":"0000-0001-9048-1941","position":6,"is_corresponding":false},{"id":313600,"name":"Keith P. Smith","orcid":"0000-0003-2672-6339","position":7,"is_corresponding":false},{"id":11309,"name":"Ethan M. Lange","orcid":"0000-0001-7075-4287","position":8,"is_corresponding":false},{"id":24984,"name":"Leslie A. Lange","orcid":"0000-0002-4220-6766","position":9,"is_corresponding":false},{"id":524295,"name":"Laure El ghormli","orcid":"0000-0003-4223-8407","position":10,"is_corresponding":false},{"id":381343,"name":"Kimberly L. Drews","orcid":"0000-0001-9287-2540","position":11,"is_corresponding":false},{"id":334625,"name":"Philip Zeitler","orcid":"0000-0001-5756-7858","position":12,"is_corresponding":false},{"id":276837,"name":"Jane E.B. Reusch","orcid":"0000-0001-8620-1003","position":13,"is_corresponding":false},{"id":255268,"name":"Vera Fridman","orcid":"0000-0003-0068-8549","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:13:39.186262Z","pmid":"37341347","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}