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Title: Peripheral nerve pathology in diabetic neuropathy : human and animal studies
Author: Walker, David
Awarding Body: University of Manchester : University of Manchester
Current Institution: University of Manchester
Date of Award: 2001
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This thesis presents data from detailed light and electronmicroscopic studies in nerve from subjects with impaired glucose tolerance and diabetic patients with varying degrees of diabetic neuropathy. In addition, nerve pathology is characterised in patients with diabetic amyotrophy and two animal models; the streptozotocin-diabetic rat and the streptozotocinlalloxan-diabetic dog. Impaired glucose tolerance subjects demonstrate no abnormalities of the myelinated fibres whereas patients without clinical or neurophysiological evidence of neuropathy demonstrate myelinated fibre demyelination without axonal degeneration which progresses to myelinated fibre loss in patients with mild and severe neuropathy. Unmyelinated fibres exhibit pathological changes in subjects with impaired glucose tolerance in the form of early degeneration which progresses to a degree of regeneration and degeneration in patients without clinical manifestations of neuropathy and continued regeneration despite a high degree of degeneration in patients with established neuropathy. Endoneurial capillary morphology has been quantified and demonstrates an initial decrease in luminal area in both subjects with impaired glucose tolerance and diabetic patients without neuropathy followed by an increase in luminal area in patients with mild and severe forms of neuropathy. Endothelial cell hyperplasia and capillary basement membrane thickening are present prior to the development of diabetes in impaired glucose tolerance subjects and demonstrate an increase in diabetic patients progressing with the severity of neuropathy. Young Type 1 diabetic patients demonstrate myelinated fibre demyelination without axonal degeneration. Neither unmyelinated fibre degeneration or regeneration is demonstrated in these patients but a degree of unmyelinated fibre axonal atrophy is present. Endoneurial capillary morphology has been assessed in young Type 1 diabetic patients and a decrease in luminal area along with endothelial cell hyperplasia and basement membrane thickening have been characterised. Patients with painful diabetic amyotrophy are characterised by a reduction in proximal nerve conduction velocity. The underlying pathology consists of myelinated fibre degeneration and a reduction in axon calibre, which may constitute a preferential reduction in larger fibres, and unmyelinated fibre degeneration and regeneration. These changes may form a pathological basis for the painful symptoms experienced by these patients. Morphometric studies on peripheral nerve from animal models have demonstrated limited abnormalities in nerve fibres and endoneurial capillaries In the streptozotocin-diabetic rat. The streptozotocinialloxan diabetic dog demonstrates few abnormalities in peripheral nerve consisting mainly of an increase in basement membrane thickening of the endoneurial capillaries. In summary, this thesis has provided detailed morphometric quantification of both myelinated and unmyelinated fibre pathology in impaired glucose tolerance subjects, diabetic patients and animal models of diabetic neuropathy, demonstrating important abnormalities that occur prior to diabetes and in early diabetic neuropathy. In addition, proximal nerve pathology has been characterised in patients with diabetic amyotrophy. Endoneurial capillary pathology has been quantified and provides further evidence of the role of microangiopathy in the pathogenesis of diabetic neuropathy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available