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Aspirin in type 2 diabetes, a randomised controlled study: effect of different doses on inflammation, oxidative stress, insulin resistance and endothelial function

Authors

  • R. P. Raghavan,

    Corresponding author
    1. Wolverhampton Diabetes Centre, New Cross Hospital, Wolverhampton, UK
    2. School of Pharmacy and Biomedical Sciences, University Of Portsmouth, Portsmouth, UK
    3. Academic Department of Diabetes and Endocrinology, Diabetes Centre, Queen Alexandra Hospital, Portsmouth, UK
    • Correspondence to:

      Dr Rajeev P. Raghavan, MD, MRCP (UK) Wolverhampton Diabetes Centre, New Cross Hospital, Wednesfield Road, Wolverhampton WV10 0QP, UK

      Tel.: 01902 695314

      Fax: 01902 695325

      Email: rajeevraghavan@nhs.net

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  • D. W. Laight,

    1. School of Pharmacy and Biomedical Sciences, University Of Portsmouth, Portsmouth, UK
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  • M. H. Cummings

    1. Academic Department of Diabetes and Endocrinology, Diabetes Centre, Queen Alexandra Hospital, Portsmouth, UK
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  • Disclosure

    The authors declare no conflict of interest in relation to this study.

Summary

Objectives

The effect of aspirin upon platelet function is well documented although experimental studies suggest that aspirin may also affect oxidative stress, vascular inflammation, endothelial dysfunction and dysglycaemia. The optimal dose of aspirin for cardiovascular protection in type 2 diabetes is still debated. We examined the effects of different doses of aspirin upon these novel markers of cardiovascular risk and any association between aspirin-mediated changes in these markers.

Methodology

Subjects with type 2 diabetes attended for baseline evaluation including BMI, glycaemic and lipid markers, endothelial function (photoplethysmography), insulin resistance (HOMA), inflammation (sVCAM-1 and Hs-CRP) and markers of oxidative stress [total anti-oxidant status (TAOS and FRAP), whole blood total glutathione (GSH) assays]. Subjects then received in random, sequential, blinded fashion aspirin 75 mg day−1, aspirin 300 mg day−1, aspirin 3.6 g day−1 or placebo for 2 weeks with a 2-week washout. The above investigations were repeated after each intervention. Aspirin-related changes compared with placebo were analysed using repeated measures ANOVA.

Results

Subjects = 17 (M – 12; F – 5), mean age – 57.4 ± 9.1 years (mean ± 1 SD), HbA1c – 63 ± 13 mmol mol−1 (7.9 ± 1.2%), total cholesterol 4.57 ± 1.01 mmol l−1. At baseline TAOS value was 59.3 ± 9.7 μM AEAC (Ascorbate Equivalent Anti-oxidant Concentration), glutathione 302.2 ± 183.3 mmol l−1 and FRAP 0.86 ± 0.23 mM FeII. None of the aspirin doses had a significant impact upon BMI, blood pressure, lipid parameters, insulin sensitivity (HOMA), FRAP, TAOS, GSH, endothelial function, glycaemic control (fructosamine) or inflammation (sVCAM-1 and HsCRP).

Conclusions

Aspirin exhibited no significant dose-dependent effect on markers of vascular inflammation, oxidative stress, insulin resistance and endothelial function (photoplethysmography) when used in type 2 diabetes over a 2-week period. (Clinical trials registration: NCT00898950, EUDRACT:2004-001418-14)

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