Oxidative stress is present in atherosclerotic peripheral arterial disease and further increased by diabetes mellitus

OBJECTIVE: Atherosclerosis, which is associated with increased oxidative stress, may be widespread and more advanced in both complicated and uncomplicated diabetics than in healthy, age-matched non diabetic controls. The development of microangiopathy and the early development of microangiopathy and the early development of macroangiopathy which occurs in diabetes have unclear aetiology. We have previously shown an increase in the products of free radical activity in conventional atherosclerosis and this study has considered whether there us a further increase in this oxidative stress in diabetics.

EXPERIMENTAL DESIGN: We measured oxidation by free radicals as lipid peroxides (malondialdehyde) and plasma thiols in 19 insulin dependent diabetic patients with retinopathy or microproteinuria but no clinical evidence of large vessel disease, 19 non diabetic patients with obstructive peripheral arterial disease confirmed by angiography and 19 asymptomatic matched healthy control subjects.

PATIENTS: The patients were recruited from either the local diabetic or vascular surgery clinics.

RESULTS: There were significant increases in oxidative stress in diabetic patients compared to control subjects with increased malondialdehyde 9.2 mumol/l (7.1-11.2) versus 7.65 mumol/l (5.4-9.6, p < 0.01 Mann Whitney test) and reduced plasma thiols 458 mumol/l (294-595) versus 506 mumol/l (433-589, p < 0.05). Those non-diabetic patients with obstructive peripheral arterial disease also had significantly increased malondialdehyde levels at 8.4 mumol/l (6.5-10.1, p < 0.05) and reduced plasma thiols 435 mumol/l (361-462, p < 0.05) compared to controls. The difference between patients with conventional atherosclerotic peripheral arterial disease and those with additional diabetes was significant for malondialdehyde (p < 0.05).

CONCLUSIONS: These data confirm the oxidative stress that exists in atherosclerotic peripheral arterial disease and suggest that diabetic patients with microangiopathy have an increase in this oxidative stress which may contribute to their early development of atherosclerosis.