Diabetologia. 2012 Nov;55(11):2920-8.

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

Treweeke AT, Winterburn TJ, Mackenzie I, Barrett F, Barr C, Rushworth GF, Dransfield I, MacRury SM, Megson IL.

Free Radical Research Facility, Department of Diabetes & Cardiovascular Science, University of the Highlands & Islands, Centre for Health Science, Inverness IV2 3JH, UK.


Abstract

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.

PMID: 22935960

 

Supplement:

This important work shows that supplementation of the crucial antioxidant, glutathione (GSH), in platelets of patients with type 2 diabetes can reduce platelet conjugation to monocytes – a marker of cardiovascular risk. Importantly, the effect showed close inverse correlation with pre-existing glutathione levels in platelets, suggesting a stratified approach to utilisation of this as a prophylactic therapy in patients with type 2 diabetes. The issue is particularly important because the mainstay of anti-thrombotic therapy, aspirin, is no longer recommended in patients with type 2 diabetes who have not yet experienced a thrombotic event.

 

Ian Megson-1

Reduction in CD14+/CD41a+ (platelet-monocyte conjugate) events from a patient before (baseline) and after (2 h) oral NAC dosing.

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