In this thesis, microvascular and neuronal function in the foot skin of subjects with Type 2 diabetes was investigated to determine whether abnormalities exist, if and so to determine the role of such abnormalities in the pathogenesis of ulceration and its healing. The principle findings of the thesis are: - In the absence of macrovascular disease, impaired nerve function, (large and small nerve fibre) is associated with foot ulceration in Type 2 diabetic subjects; however, there appears to be no additional predictive value in measuring small fibre function using sophisticated methods over large fibre function assessed by measuring vibration sensation. Neither Tcp02 nor the more complicated measurements of microvascular hyperaemic responses were able to discriminate between those with and without ulceration. This would suggest that such tests may not be of benefit in identifying those at greater risk of foot ulceration. The 'LDIflare' a novel, simple, non-invasive and objective method to assess small fibre function is described. This demonstrates that C-fibre dysfunction occurs relatively early in Type 2 diabetes before it is detected by the currently available methods. Thus, the LDlflare may be of value in screening for early diabetic neuropathy. The LDlflare correlates well with skin nerve fibre density and in addition demonstrates functional changes in subjects with painful neuropathy when structural nerve fibre changes are less well marked. This suggests the LDlflare may have an advantage over skin biopsies and quantitative sensory testing in diagnosing painful diabetic neuropathy. The rate of wound closure was identical between control subjects and diabetic patients despite a significant reduction in microvascular blood flow, epidermal and dermal VEGF-A and blood vessel VEGFR-2 expression, the LDlflare response and dermal nerve fibre density. These studies are important in directing further research into these devastating and expensive complications of diabetes.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:445539 |
| Date | January 2007 |
| Creators | MuraliKrishnan, Singhan Thulasiraman |
| Publisher | University of East Anglia |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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