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Glyoxal in hyperglycaemic ischemic stroke – a cohort study

BACKGROUND: Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hype...

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Autores principales: Rhein, Sina, Inderhees, Julica, Herrmann, Oliver, Othman, Alaa, Begemann, Kimberly, Fleming, Thomas, Nawroth, Peter P., Klika, Karel D., Isa, Rakad, König, Inke R., Royl, Georg, Schwaninger, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10339542/
https://www.ncbi.nlm.nih.gov/pubmed/37438755
http://dx.doi.org/10.1186/s12933-023-01892-7
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author Rhein, Sina
Inderhees, Julica
Herrmann, Oliver
Othman, Alaa
Begemann, Kimberly
Fleming, Thomas
Nawroth, Peter P.
Klika, Karel D.
Isa, Rakad
König, Inke R.
Royl, Georg
Schwaninger, Markus
author_facet Rhein, Sina
Inderhees, Julica
Herrmann, Oliver
Othman, Alaa
Begemann, Kimberly
Fleming, Thomas
Nawroth, Peter P.
Klika, Karel D.
Isa, Rakad
König, Inke R.
Royl, Georg
Schwaninger, Markus
author_sort Rhein, Sina
collection PubMed
description BACKGROUND: Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke. METHODS: In 135 patients with acute stroke, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure glyoxal, methylglyoxal and several of their glycated amino acid derivatives in serum. Results were verified in a second cohort of 61 stroke patients. The association of serum concentrations with standard stroke outcome scales (NIHSS, mRS) was tested. RESULTS: Glucose, glyoxal, methylglyoxal, and the glyoxal-derived glycated amino acid N(δ)-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) were positively correlated with a bad stroke outcome at 3 months as measured by mRS90, at least in one of the two cohorts. However, the glycated amino acids N(ε)-carboxyethyllysine (CEL) and in one cohort pyrraline showed an inverse correlation with stroke outcome probably reflecting lower food intake in severe stroke. Patients with a poor outcome had higher serum concentrations of glyoxal and methylglyoxal. CONCLUSIONS: The glucose-derived α-dicarbonyl glyoxal and glycated amino acids arising from a reaction with glyoxal are associated with a poor outcome in ischemic stroke. Thus, lowering α-dicarbonyls or counteracting their action could be a therapeutic strategy for hyperglycaemic stroke. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-023-01892-7.
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spelling pubmed-103395422023-07-14 Glyoxal in hyperglycaemic ischemic stroke – a cohort study Rhein, Sina Inderhees, Julica Herrmann, Oliver Othman, Alaa Begemann, Kimberly Fleming, Thomas Nawroth, Peter P. Klika, Karel D. Isa, Rakad König, Inke R. Royl, Georg Schwaninger, Markus Cardiovasc Diabetol Research BACKGROUND: Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke. METHODS: In 135 patients with acute stroke, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure glyoxal, methylglyoxal and several of their glycated amino acid derivatives in serum. Results were verified in a second cohort of 61 stroke patients. The association of serum concentrations with standard stroke outcome scales (NIHSS, mRS) was tested. RESULTS: Glucose, glyoxal, methylglyoxal, and the glyoxal-derived glycated amino acid N(δ)-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) were positively correlated with a bad stroke outcome at 3 months as measured by mRS90, at least in one of the two cohorts. However, the glycated amino acids N(ε)-carboxyethyllysine (CEL) and in one cohort pyrraline showed an inverse correlation with stroke outcome probably reflecting lower food intake in severe stroke. Patients with a poor outcome had higher serum concentrations of glyoxal and methylglyoxal. CONCLUSIONS: The glucose-derived α-dicarbonyl glyoxal and glycated amino acids arising from a reaction with glyoxal are associated with a poor outcome in ischemic stroke. Thus, lowering α-dicarbonyls or counteracting their action could be a therapeutic strategy for hyperglycaemic stroke. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-023-01892-7. BioMed Central 2023-07-12 /pmc/articles/PMC10339542/ /pubmed/37438755 http://dx.doi.org/10.1186/s12933-023-01892-7 Text en © The Author(s) 2023 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Rhein, Sina
Inderhees, Julica
Herrmann, Oliver
Othman, Alaa
Begemann, Kimberly
Fleming, Thomas
Nawroth, Peter P.
Klika, Karel D.
Isa, Rakad
König, Inke R.
Royl, Georg
Schwaninger, Markus
Glyoxal in hyperglycaemic ischemic stroke – a cohort study
title Glyoxal in hyperglycaemic ischemic stroke – a cohort study
title_full Glyoxal in hyperglycaemic ischemic stroke – a cohort study
title_fullStr Glyoxal in hyperglycaemic ischemic stroke – a cohort study
title_full_unstemmed Glyoxal in hyperglycaemic ischemic stroke – a cohort study
title_short Glyoxal in hyperglycaemic ischemic stroke – a cohort study
title_sort glyoxal in hyperglycaemic ischemic stroke – a cohort study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10339542/
https://www.ncbi.nlm.nih.gov/pubmed/37438755
http://dx.doi.org/10.1186/s12933-023-01892-7
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