Atherothrombosis and oxidative stress: The connection and correlation in diabetes

Background: Hyperglycaemia-induced depletion of reduced glutathione (GSH) causes erythrocyte oxidative stress (EOS), which leads to vascular events including exacerbation of thrombotic events evidenced by changes in D-dimer level. It would, therefore, appear that there is a complex link between GSH and D-dimer, which are part of an emerging array of biomarkers associated with diabetes. The objective of this study was to investigate evidence of correlation between levels of plasma D-dimer and erythrocyte GSH in diabetes disease progression. Subjects and methods: A cohort of 69 subjects were selected based on medical history plus clinical findings and equally divided into control, prediabetes and diabetes groups, matched for age and sex. Plasma D-dimer and erythrocyte reduced glutathione (GSH) were determined and separated into quartiles as a means of indicating disease severity. Statistical analysis was by Pearson's correlation coefficient. Results: Of the three groups, only the diabetes group showed any correlation between GSH and D-dimer. Of importance is that for increasing GSH, the second quartile range of GSH (x̄ ± SD = 45 ± 22 mg/100ml) showed a statistically significant negative correlation for ranked D-dimer (x̄ ± SD = 1055 ± 828 μg/l; r = -0.88; P < 0.02). The fourth quartile GSH range (x̄ ± SD = 79 ± 40 mg/100 ml) showed a statistically significant positive correlation with D-dimer (x̄ ± SD = 1055 ± 828 μg/l; r = 0.91; P < 0.02). Thus, within the diabetes group only, the increasing level of oxidative stress as measured by GSH first indicates a reduction in D-dimer followed by a rise in D-dimer, which led to the proposal of a two-part process of atherosclerosis that reconciles previous contradictory findings. Conclusions: This study provides not only evidence of a correlation between oxidative stress level and fibrinolysis in diabetes, but also an explanation of why previous studies have found both hypo- or hyperfibrinolysis associated with diabetes.