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Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway

AIMS/HYPOTHESIS: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological...

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Autores principales: Tigchelaar, Celien, van Zuylen, Mark L., Hulst, Abraham H., Preckel, Benedikt, van Beek, André P., Kema, Ido P., Hermanides, Jeroen, Absalom, Anthony R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174140/
https://www.ncbi.nlm.nih.gov/pubmed/35380232
http://dx.doi.org/10.1007/s00125-022-05693-7
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author Tigchelaar, Celien
van Zuylen, Mark L.
Hulst, Abraham H.
Preckel, Benedikt
van Beek, André P.
Kema, Ido P.
Hermanides, Jeroen
Absalom, Anthony R.
author_facet Tigchelaar, Celien
van Zuylen, Mark L.
Hulst, Abraham H.
Preckel, Benedikt
van Beek, André P.
Kema, Ido P.
Hermanides, Jeroen
Absalom, Anthony R.
author_sort Tigchelaar, Celien
collection PubMed
description AIMS/HYPOTHESIS: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations. METHODS: This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels. RESULTS: Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. CONCLUSIONS/INTERPRETATION: Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities. GRAPHICAL ABSTRACT: [Image: see text]
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spelling pubmed-91741402022-06-09 Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway Tigchelaar, Celien van Zuylen, Mark L. Hulst, Abraham H. Preckel, Benedikt van Beek, André P. Kema, Ido P. Hermanides, Jeroen Absalom, Anthony R. Diabetologia Article AIMS/HYPOTHESIS: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations. METHODS: This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels. RESULTS: Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. CONCLUSIONS/INTERPRETATION: Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities. GRAPHICAL ABSTRACT: [Image: see text] Springer Berlin Heidelberg 2022-04-05 2022 /pmc/articles/PMC9174140/ /pubmed/35380232 http://dx.doi.org/10.1007/s00125-022-05693-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tigchelaar, Celien
van Zuylen, Mark L.
Hulst, Abraham H.
Preckel, Benedikt
van Beek, André P.
Kema, Ido P.
Hermanides, Jeroen
Absalom, Anthony R.
Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway
title Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway
title_full Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway
title_fullStr Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway
title_full_unstemmed Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway
title_short Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway
title_sort elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174140/
https://www.ncbi.nlm.nih.gov/pubmed/35380232
http://dx.doi.org/10.1007/s00125-022-05693-7
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