Premature vascular disease is an important cause of morbidity and mortality in Western countries and two groups particularly at risk from premature and extensive vascular disease are diabetic and hyperlipidaemic patients. In addition diabetics develop a specific microvascular disease affecting the capillaries resulting in retinopathy, nephropathy and contributing to neuropathy. Many factors may be involved in the pathogenesis of vascular disease in these two patient groups. In this thesis particular attention has been given to the detection of enhanced platelet function as platelets are important in thrombosis which is often the final event leading to the occlusion of an atheromatous artery and platelets may contribute to the development of vascular disease. The results reported in this thesis suggest that in diabetic and hyperlipidaemic patients there is evidence of increased in vivo platelet release reaction as evidenced by the finding of elevated levels of the platelet-specific proteins, thromboglobulin and platelet factor 4 in platelet-poor plasma from these patients. There is evidence also of enhanced activity of the platelet prostaglandin pathway in response to stimulation with arachidonic acid in these patients. These abnormalities did not appear to be related to pre-existing vascular disease in the patients studied. Furthermore platelets from diabetic subjects show diminished sensitivity to the anti-aggregatory effects of prostacyclin and enhanced platelet aggregation to the aggregatory agonists collagen and arachidonic acid when studied in whole blood. In addition the experimental diabetic rat produces less aortic prostacyclin than control rats. These results provide evidence of enhanced platelet function in patients with diabetes and hyperlipidaemia which may contribute to their increased vascular risk. However these conclusions can only remain tentative until it is possible to perform long-term prospective studies in these patients.
|Date of Award||1985|