title: N-Acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial.
abstract: OBJECTIVE
  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
  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.
  
  
  BACKGROUND
  Chief Scientist Office (CZB/4/622), Scottish Funding Council, Highlands & Islands Enterprise and European Regional Development Fund.
  
  
  BACKGROUND
  isrctn.org ISRCTN89304265.
authors.affiliation: Free Radical Research Facility, Department of Diabetes & Cardiovascular Science, University of the Highlands & Islands, Centre for Health Science, Inverness IV2 3JH, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Treweeke
authors.forename: T J
authors.initials: TJ
authors.lastname: Winterburn
authors.forename: I
authors.initials: I
authors.lastname: Mackenzie
authors.forename: F
authors.initials: F
authors.lastname: Barrett
authors.forename: C
authors.initials: C
authors.lastname: Barr
authors.forename: G F
authors.initials: GF
authors.lastname: Rushworth
authors.forename: I
authors.initials: I
authors.lastname: Dransfield
authors.forename: S M
authors.initials: SM
authors.lastname: MacRury
authors.forename: I L
authors.initials: IL
authors.lastname: Megson
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage* / Q000097:blood; D000284:Administration, Oral; D000368:Aged; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002450:Cell Communication / Q000187:drug effects*; D055252:Cell-Derived Microparticles / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000097:blood; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010919:Placebos
chemical_list: D016166:Free Radical Scavengers; D007004:Hypoglycemic Agents; D010919:Placebos; D005978:Glutathione; D000111:Acetylcysteine