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

Author:

Määttä Laura L.12ORCID,Andersen Signe T.12,Parkner Tina3,Hviid Claus V.B.34,Bjerg Lasse25ORCID,Kural Mustafa A.6,Charles Morten25,Søndergaard Esben2,Kuhle Jens78,Tankisi Hatice6,Witte Daniel R.25ORCID,Jensen Troels S.1

Affiliation:

1. 1Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

2. 2Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

3. 3Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

4. 4Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

5. 5Department of Public Health, Aarhus University, Aarhus, Denmark

6. 6Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark

7. 7Department of Neurology, University of Basel, Basel, Switzerland

8. 8Multiple Sclerosis Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel, Basel, Switzerland

Abstract

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 Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care-Denmark (ADDITION-Denmark) cohort of people with screen-detected type 2 diabetes. Biobank samples acquired at the ADDITION-Denmark 5- and 10-year follow-ups were analyzed for serum NfL (s-NfL) using single-molecule array, and the results were compared with 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 with −DPN). s-NfL at the 5-year follow-up was positively associated with nerve conduction studies at the 10-year follow-up (P = 0.02 to <0.001), but not with DPN risk. Areas under the curve (AUCs) for s-NfL were not inferior to AUCs for the Michigan Neuropathy Screening Instrument questionnaire score or vibration detection thresholds. Higher yearly s-NfL increase was associated with higher DPN risk (odds ratio 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.

Funder

Servier Denmark A/S

ASTRA Denmark

Danish Foundation of the National Board of Health

Danish Medical Research Council

Novo Nordisk Scandinavia AB

Danish Diabetes and Endocrine Academy

HemoCue Denmark A/S

Department of Clinical Biochemistry, Aarhus University Hospital

Novo Nordisk Fonden

Danish Council for Strategic Research

Danish Center for Evaluation and Health Technology Assessment

Novo Nordisk UK

Aarhus University Research Foundation

National Health Services in the former counties of Copenhagen, Aarhus, Ringkøbing, Ribe and the county of Southern Jutland in Denmark

Steno Diabetes Center Aarhus

Pfizer Denmark

GlaxoSmithKline Pharma Denmark

Danish Research Foundation for General Practice

A.P. Møller Foundation

Riisfort Foundation

Publisher

American Diabetes Association

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