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

posted on 2024-03-19, 19:30 authored by Laura L. Määttä, Signe T. Andersen, Tina Parkner, Claus V.B. Hviid, Lasse Bjerg, Mustafa A. Kural, Morten Charles, Esben Søndergaard, Jens Kuhle, Hatice Tankisi, Daniel R. Witte, Troels S. Jensen

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.


This work was supported by research grants from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation (grant number NNF17SA0031406); and from Steno Diabetes Center Aarhus, Aarhus University Hospital. The work is also part of the International Diabetic Neuropathy Consortium research program, which is supported by a Novo Nordisk Foundation Challenge Program grant (grant number NNF14OC0011633). Additional support was received by the A.P. Møller Foundation, the Riisfort Foundation and the Department of Clinical Biochemistry, Aarhus University Hospital. ADDITION-Denmark was funded by the National Health Services in the former counties of Copenhagen, Aarhus, Ringkøbing, Ribe and the county of Southern Jutland in Denmark; the Danish Council for Strategic Research; the Danish Research Foundation for General Practice; the Novo Nordisk Foundation; the Danish Center for Evaluation and Health Technology Assessment; the Danish Foundation of the National Board of Health; the Danish Medical Research Council; the Aarhus University Research Foundation; Novo Nordisk Scandinavia AB; Novo Nordisk UK; ASTRA Denmark; Pfizer Denmark; GlaxoSmithKline Pharma Denmark; Servier Denmark A/S; and HemoCue Denmark A/S.


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