Oxidative stress and cardiovascular ageing in diabetes
Oxidative stress is thought to be elevated in diabetes as a consequence of hyperglycaemia. This thesis investigates oxidative DNA damage in diabetes, which may contribute to accelerated vascular ageing. Telomeric and mitochondrial DNA are two areas of the genome that may be more susceptible to oxidative stress and were therefore investigated.;51 patients with diabetes (aged 31-78 years) and 101 healthy controls (aged 19-75 years) were recruited. 51 of the controls were age- and sex-matched to be patient group. For both populations physiological profiles were obtained and pulse wave velocity (PWV), an index of vascular stiffness, was measured. Oxidative DNA damage was also investigated in peripheral blood using the comet assay, and in more depth by measuring terminal restriction fragment (TRF) lengths and quantifying mitochondrial DNA (mtDNA) content. PWV increased with age in both study groups (p<0.001) and was significantly higher in the patient group (8.00 +/- 2.89 versus 7.29 +/- 1.64 m/s; p=0.006), suggesting accelerated vascular ageing in diabetes. This was accompanied by elevated levels of oxidative DNA damage; 25.81 +/- 1.18 versus 21.40 +/- 0.81% Tail DNA (p=0.003) in patients and controls respectively. TRF length inversely correlated with age in both groups (p<0.05), with similar rates of attrition, and although they were shorter in the patients with diabetes, this was not significant (p=0.10). Quantification of mtDNA revealed significantly lower levels in the patients with diabetes compared to the controls (0.014 versus 0.016; p=0.020). There is accelerated vascular ageing in diabetes, which is accompanied by elevated oxidative DNA damage, and a decrease in mtDNA, but no alteration in TRF length compared to a healthy control population. The mechanisms underlying these alterations are unknown with the lack of correlations with glycaemic control suggesting it is not the sole cause but it may still contribute.