Associations between multiple neurological biomarkers and distal sensorimotor polyneuropathy: KORA F4/FF4 study

Author:

Herder Christian123ORCID,Thorand Barbara456ORCID,Strom Alexander12ORCID,Rathmann Wolfgang12ORCID,Heier Margit47ORCID,Koenig Wolfgang8910ORCID,Morrison Helen1112,Ziegler Dan1ORCID,Roden Michael123ORCID,Peters Annette456ORCID,Bönhof Gidon J.123ORCID,Maalmi Haifa12ORCID

Affiliation:

1. Institute for Clinical Diabetology German Diabetes Center Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf Düsseldorf Germany

2. German Center for Diabetes Research (DZD) Partner Düsseldorf Munich Germany

3. Department of Endocrinology and Diabetology Medical Faculty and University Hospital Düsseldorf Heinrich Heine University Düsseldorf Düsseldorf Germany

4. Institute of Epidemiology Helmholtz Zentrum München German Research Center for Environmental Health Munich Germany

5. German Center for Diabetes Research (DZD) Partner Neuherberg Partner Düsseldorf Munich Germany

6. Institute for Medical Information Processing Biometry and Epidemiology Ludwig‐Maximilians‐Universität Munich Germany

7. KORA Study Centre University Hospital of Augsburg Augsburg Germany

8. Institute of Epidemiology and Medical Biometry University of Ulm Ulm Germany

9. Deutsches Herzzentrum München Technische Universität München Munich Germany

10. German Centre for Cardiovascular Research (DZHK e.V.) Partner Site München Heart Alliance Munich Germany

11. Leibniz Institute on Aging – Fritz Lipmann Institute Jena Germany

12. Faculty of Biological Sciences Friedrich–Schiller University Jena Germany

Abstract

AbstractAimsThe aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN).Materials and MethodsCross‐sectional analyses were based on 1032 participants aged 61–82 years from the population‐based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1‐SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini–Hochberg procedure.ResultsHigher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), pB‐H = 0.044) and PDGFRα (platelet‐derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), pB‐H = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM‐B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all pB‐H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all pB‐H>0.05).ConclusionsThis study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.

Funder

Bundesministerium für Gesundheit

European Foundation for the Study of Diabetes

Bundesministerium für Bildung und Forschung

Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen

Publisher

Wiley

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