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Title: Some abnormalities of platelet and leucocyte function, and changes in free radical activity : their possible roles in the development of diabetic microvascular complications
Author: Collier, A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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Microangiopathy is a major cause of morbidity and mortality in diabetes mellitus, and its pathogenesis remains poorly understood. Abnormalities of both the in vivo and in vitro haemostasis have been extensively reported. Particularly changes in platelet function have been described in cross-sectional studies, and cause-end-effect relationships have been postulated. It is also suggested that neutrophil accumulation at sites of inflammation, including vascular endothelium, can induce tissue damage. Three classes of mediators are particularly likely to participate in the pathogenesis of neutrophil-mediated vascular injury: granule enzymes, reactive oxygen metabolites, and products of membrane phospholipids. The aims of this thesis were to investigate changes in platelet function in insulin-dependent diabetic patients in relation to glycaemic control, and microvascular disease in the form of retinopathy. In addition, the changes in platelet function in non-insulin-dependent diabetic patients at diagnosis, and the effect of glycaemic control and oral hypoglycaemic therapy were assessed. As a measure of neutrophil activity, neutrophil elastase was measured in insulin-dependent diabetic patients with retinopathy. The changes in elastase levels in response to acute insulin-induced hypoglycaemia in non-diabetic subjects were also evaluated. A further aim was to measure a marker for free radical activity in insulin-dependent diabetes. The changes in platelet density, thromboxane production and receptor sensitivity demonstrated are consistent with platelets from diabetic patients being hyperaggregable and contributing towards microvascular disease. The increase in neutrophil elastase levels in insulin-dependent diabetic patients, and the rise in normals in response to hypoglycaemia are consistent with leucocyte-endothelial interaction contributing towards diabetic microvascular disease. Although the marker for free radical activity was not increased in the retinopathic insulin-dependent diabetic patients studied, it is probable that abnormalities of lipid metabolism related to free radical activity may still contribute to diabetic microvascular disease. Although good glycaemic control can delay the onset and slow the progress of diabetic complications, specific therapeutic agents that interfere with haemostasis, leucocyte function and free radical activity may also have a protective role in the development of diabetic complications. In addition, use of these agents may also give greater understanding of the aetiopathogenesis of diabetic microangiopathy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available