title: Aspirin in type 2 diabetes, a randomised controlled study: effect of different doses on inflammation, oxidative stress, insulin resistance and endothelial function.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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. (
  
  
  BACKGROUND
  NCT00898950, EUDRACT:2004-001418-14).
authors.affiliation: Wolverhampton Diabetes Centre, New Cross Hospital, Wolverhampton, UK; School of Pharmacy and Biomedical Sciences, University Of Portsmouth, Portsmouth, UK; Academic Department of Diabetes and Endocrinology, Diabetes Centre, Queen Alexandra Hospital, Portsmouth, UK.
authors.forename: R P
authors.initials: RP
authors.lastname: Raghavan
authors.forename: D W
authors.initials: DW
authors.lastname: Laight
authors.forename: M H
authors.initials: MH
authors.lastname: Cummings
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D014657:Vasculitis / Q000517:prevention & control
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D005978:Glutathione; D001241:Aspirin