Deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathy

Introduction The determinants and mechanisms contributing to diabetic sensorimotor polyneuropathy (DSPN) remain unclear. Since neuroinflammation and altered nerve regeneration have been implicated in the pathogenesis of both DSPN and neuropathic pain, we hypothesized that the corresponding biomarker...

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Main Authors: Barbara Thorand, Annette Peters, Dan Ziegler, Alexander Strom, Gidon J Bönhof, Julia M Kannenberg, Margit Heier, Wolfgang Rathmann, Christina Meisinger, Michael Roden, Christian Herder
Format: Article
Language:English
Published: BMJ Publishing Group 2019-05-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/7/1/e000752.full
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author Barbara Thorand
Annette Peters
Dan Ziegler
Alexander Strom
Gidon J Bönhof
Julia M Kannenberg
Margit Heier
Wolfgang Rathmann
Christina Meisinger
Michael Roden
Christian Herder
author_facet Barbara Thorand
Annette Peters
Dan Ziegler
Alexander Strom
Gidon J Bönhof
Julia M Kannenberg
Margit Heier
Wolfgang Rathmann
Christina Meisinger
Michael Roden
Christian Herder
author_sort Barbara Thorand
collection DOAJ
description Introduction The determinants and mechanisms contributing to diabetic sensorimotor polyneuropathy (DSPN) remain unclear. Since neuroinflammation and altered nerve regeneration have been implicated in the pathogenesis of both DSPN and neuropathic pain, we hypothesized that the corresponding biomarkers could be associated with DSPN in general and could have the potential to discriminate between the painful and painless DSPN entities.Methods In a cross-sectional study using multimarker proximity extension assay technology we assessed 71 serum biomarkers including cytokines, chemokines, growth factors, receptors, and others in patients with type 2 diabetes with DSPN (DSPN+) (n=304) or without DSPN (DSPN−) (n=158) and persons with normal glucose tolerance (NGT) without polyneuropathy (n=354).Results After adjustment for multiple testing and sex, age, body mass index, HbA1c, and smoking, the serum levels of 17 biomarkers (four cytokines, five chemokines, four growth factors, two receptors, two miscellaneous) were lower in DSPN+ than in DSPN− and NGT. In DSPN+, six of these biomarkers were associated with peripheral nerve function. The concentrations of 15 other biomarkers differed between NGT and both DSPN+ and DSPN−, but not between DSPN+ and DSPN−. No differences in biomarker levels were found between patients with painful (n=164) and painless DSPN (n=140).Conclusions Deficits in systemic cytokines, chemokines, and growth factors promoting nerve regeneration in patients with type 2 diabetes are linked to polyneuropathy in general but not specifically to the painful or painless entity.Trial registration number NCT02243475.
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spelling doaj-art-e55e3963d5a54ce98e6c84f1efb770792024-12-15T20:45:09ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972019-05-017110.1136/bmjdrc-2019-000752Deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathyBarbara Thorand0Annette Peters1Dan Ziegler2Alexander Strom3Gidon J Bönhof4Julia M Kannenberg5Margit Heier6Wolfgang Rathmann7Christina Meisinger8Michael Roden9Christian Herder10Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany3 Institute of Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Health and Environment, Neuherberg, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, GermanyInstitute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, GermanyGerman Center for Diabetes Research, Partner Düsseldorf, Neuherberg, GermanyIndependent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany2German Diabetes Center, Düsseldorf, GermanyIntroduction The determinants and mechanisms contributing to diabetic sensorimotor polyneuropathy (DSPN) remain unclear. Since neuroinflammation and altered nerve regeneration have been implicated in the pathogenesis of both DSPN and neuropathic pain, we hypothesized that the corresponding biomarkers could be associated with DSPN in general and could have the potential to discriminate between the painful and painless DSPN entities.Methods In a cross-sectional study using multimarker proximity extension assay technology we assessed 71 serum biomarkers including cytokines, chemokines, growth factors, receptors, and others in patients with type 2 diabetes with DSPN (DSPN+) (n=304) or without DSPN (DSPN−) (n=158) and persons with normal glucose tolerance (NGT) without polyneuropathy (n=354).Results After adjustment for multiple testing and sex, age, body mass index, HbA1c, and smoking, the serum levels of 17 biomarkers (four cytokines, five chemokines, four growth factors, two receptors, two miscellaneous) were lower in DSPN+ than in DSPN− and NGT. In DSPN+, six of these biomarkers were associated with peripheral nerve function. The concentrations of 15 other biomarkers differed between NGT and both DSPN+ and DSPN−, but not between DSPN+ and DSPN−. No differences in biomarker levels were found between patients with painful (n=164) and painless DSPN (n=140).Conclusions Deficits in systemic cytokines, chemokines, and growth factors promoting nerve regeneration in patients with type 2 diabetes are linked to polyneuropathy in general but not specifically to the painful or painless entity.Trial registration number NCT02243475.https://drc.bmj.com/content/7/1/e000752.full
spellingShingle Barbara Thorand
Annette Peters
Dan Ziegler
Alexander Strom
Gidon J Bönhof
Julia M Kannenberg
Margit Heier
Wolfgang Rathmann
Christina Meisinger
Michael Roden
Christian Herder
Deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathy
BMJ Open Diabetes Research & Care
title Deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathy
title_full Deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathy
title_fullStr Deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathy
title_full_unstemmed Deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathy
title_short Deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathy
title_sort deficits in systemic biomarkers of neuroinflammation and growth factors promoting nerve regeneration in patients with type 2 diabetes and polyneuropathy
url https://drc.bmj.com/content/7/1/e000752.full
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