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N-Acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial

AIMS/HYPOTHESIS: The aim of this study was to determine whether oral dosing with N-acetylcysteine (NAC) increases intraplatelet levels of the antioxidant, glutathione (GSH), and reduces platelet–monocyte conjugation in blood from patients with type 2 diabetes. METHODS: In this placebo-controlled ran...

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Autores principales: Treweeke, A. T., Winterburn, T. J., Mackenzie, I., Barrett, F., Barr, C., Rushworth, G. F., Dransfield, I., MacRury, S. M., Megson, I. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464379/
https://www.ncbi.nlm.nih.gov/pubmed/22935960
http://dx.doi.org/10.1007/s00125-012-2685-z
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author Treweeke, A. T.
Winterburn, T. J.
Mackenzie, I.
Barrett, F.
Barr, C.
Rushworth, G. F.
Dransfield, I.
MacRury, S. M.
Megson, I. L.
author_facet Treweeke, A. T.
Winterburn, T. J.
Mackenzie, I.
Barrett, F.
Barr, C.
Rushworth, G. F.
Dransfield, I.
MacRury, S. M.
Megson, I. L.
author_sort Treweeke, A. T.
collection PubMed
description AIMS/HYPOTHESIS: The aim of this study was to determine whether oral dosing with N-acetylcysteine (NAC) increases intraplatelet levels of the antioxidant, glutathione (GSH), and reduces platelet–monocyte conjugation in blood from patients with type 2 diabetes. METHODS: In this placebo-controlled randomised crossover study, the effect of oral NAC dosing on platelet–monocyte conjugation and intraplatelet GSH was investigated in patients with type 2 diabetes (eligibility criteria: men or post-menopausal women with well-controlled diabetes (HbA(1c) < 10%), not on aspirin or statins). Patients (n = 14; age range 43–79 years, HbA(1c) = 6.9 ± 0.9% [52.3 ± 10.3 mmol/mol]) visited the Highland Clinical Research Facility, Inverness, UK on day 0 and day 7 for each arm of the study. Blood was sampled before and 2 h after oral administration of placebo or NAC (1,200 mg) on day 0 and day 7. Patients received placebo or NAC capsules for once-daily dosing on the intervening days. The order of administration of NAC and placebo was allocated by a central office and all patients and research staff involved in the study were blinded to the allocation until after the study was complete and the data fully analysed. The primary outcome for the study was platelet–monocyte conjugation. RESULTS: Oral NAC reduced platelet–monocyte conjugation (from 53.1 ± 4.5% to 42.5 ± 3.9%) at 2 h after administration and the effect was maintained after 7 days of dosing. Intraplatelet GSH was raised in individuals with depleted GSH and there was a negative correlation between baseline intraplatelet GSH and platelet–monocyte conjugation. There were no adverse events. CONCLUSIONS/INTERPRETATION: The NAC-induced normalisation of intraplatelet GSH, coupled with a reduction in platelet–monocyte conjugation, suggests that NAC might help to reduce atherothrombotic risk in type 2 diabetes. FUNDING: Chief Scientist Office (CZB/4/622), Scottish Funding Council, Highlands & Islands Enterprise and European Regional Development Fund. TRIAL REGISTRATION: isrctn.org ISRCTN89304265 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-012-2685-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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spelling pubmed-34643792012-10-05 N-Acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial Treweeke, A. T. Winterburn, T. J. Mackenzie, I. Barrett, F. Barr, C. Rushworth, G. F. Dransfield, I. MacRury, S. M. Megson, I. L. Diabetologia Article AIMS/HYPOTHESIS: The aim of this study was to determine whether oral dosing with N-acetylcysteine (NAC) increases intraplatelet levels of the antioxidant, glutathione (GSH), and reduces platelet–monocyte conjugation in blood from patients with type 2 diabetes. METHODS: In this placebo-controlled randomised crossover study, the effect of oral NAC dosing on platelet–monocyte conjugation and intraplatelet GSH was investigated in patients with type 2 diabetes (eligibility criteria: men or post-menopausal women with well-controlled diabetes (HbA(1c) < 10%), not on aspirin or statins). Patients (n = 14; age range 43–79 years, HbA(1c) = 6.9 ± 0.9% [52.3 ± 10.3 mmol/mol]) visited the Highland Clinical Research Facility, Inverness, UK on day 0 and day 7 for each arm of the study. Blood was sampled before and 2 h after oral administration of placebo or NAC (1,200 mg) on day 0 and day 7. Patients received placebo or NAC capsules for once-daily dosing on the intervening days. The order of administration of NAC and placebo was allocated by a central office and all patients and research staff involved in the study were blinded to the allocation until after the study was complete and the data fully analysed. The primary outcome for the study was platelet–monocyte conjugation. RESULTS: Oral NAC reduced platelet–monocyte conjugation (from 53.1 ± 4.5% to 42.5 ± 3.9%) at 2 h after administration and the effect was maintained after 7 days of dosing. Intraplatelet GSH was raised in individuals with depleted GSH and there was a negative correlation between baseline intraplatelet GSH and platelet–monocyte conjugation. There were no adverse events. CONCLUSIONS/INTERPRETATION: The NAC-induced normalisation of intraplatelet GSH, coupled with a reduction in platelet–monocyte conjugation, suggests that NAC might help to reduce atherothrombotic risk in type 2 diabetes. FUNDING: Chief Scientist Office (CZB/4/622), Scottish Funding Council, Highlands & Islands Enterprise and European Regional Development Fund. TRIAL REGISTRATION: isrctn.org ISRCTN89304265 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-012-2685-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Springer-Verlag 2012-08-31 2012 /pmc/articles/PMC3464379/ /pubmed/22935960 http://dx.doi.org/10.1007/s00125-012-2685-z Text en © The Author(s) 2012 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Article
Treweeke, A. T.
Winterburn, T. J.
Mackenzie, I.
Barrett, F.
Barr, C.
Rushworth, G. F.
Dransfield, I.
MacRury, S. M.
Megson, I. L.
N-Acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial
title N-Acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial
title_full N-Acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial
title_fullStr N-Acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial
title_full_unstemmed N-Acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial
title_short N-Acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial
title_sort n-acetylcysteine inhibits platelet–monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464379/
https://www.ncbi.nlm.nih.gov/pubmed/22935960
http://dx.doi.org/10.1007/s00125-012-2685-z
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