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.


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 (xbar +/- SD = 45 +/- 22 mg/100ml) showed a statistically significant negative correlation for ranked D-dimer (xbar +/- SD = 1055 +/- 828 microg/l; r = -0.88; P < 0.02). The fourth quartile GSH range (xbar +/- SD = 79 +/- 40 mg/100 ml) showed a statistically significant positive correlation with D-dimer (xbar +/- SD = 1055 +/- 828 microg/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.
Nwose
Ezekiel U
EU
School of Community Health, Charles Sturt University, Albury, New South Wales, Australia.
Jelinek
Herbert F
HF
Richards
Ross S
RS
Tinley
Paul
P
Kerr
Philip G
PG
D000933:Antifibrinolytic Agents / Q000097:blood; D050197:Atherosclerosis / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis; D005978:Glutathione / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D013223:Statistics as Topic; D013927:Thrombosis / Q000097:blood*
D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005978:Glutathione