The University of ManchesterAbstract of thesis submitted by Hassan Fadavi for the degree of Doctor of Philosophy and titled:The mechanistic basis of vascular and neural dysfunction in patients with diabetes: The role of ethnic differencesMay 2014AbstractNeuropathy is one of the main long term complications of diabetes affecting 30-50% of patients. It is the major contributing factor for foot ulceration with a life time risk which may be as high as 25%. Hence neuropathy leads to reduced pain and pressure perception, anatomic deformities and an impaired microcirculation. More specifically, unperceived minor trauma results in cutaneous injury which when combined with an inadequate pressure induced vasodilator response leads to tissue breakdown and ulceration. Once ulcers form, healing may be delayed or difficult to achieve, particularly if infection occurs in the deeper tissues and bone which can then lead to amputation. In the UK, South Asians (people originating from India, Pakistan and Bangladesh) have an excess mortality for coronary artery disease (CAD), stroke and end-stage renal disease when compared to white Europeans. However, it has been shown that South Asian people with type 2 diabetes in the UK are only one third as likely to have a foot ulcer compared with White European diabetic patients. This has been attributed to lower levels of peripheral neuropathy in Asians, but has not been systematically explored in detail. In the present study, both neurological and vascular deficits in a group of South Asian and European patients with type II diabetes have been assessed. The results demonstrate that: • South Asian diabetic patients have poorer glycaemic control, but paradoxically lower triglycerides. This finding may be relevant to the finding that they have a lower incidence of neuropathy, as triglycerides have been related to neuropathy and foot ulceration. • South Asians compared to Europeans have better small fibre function and a trend for better structure (Intra epidermal nerve fibre density and corneal nerve morphology) and large fibre function assessed with nerve conduction studies. • South Asians have higher foot skin oxygenation and hyperaemic blood flow response to heating. • South Asians have a thicker epidermis and a trend for a better capillary density. Therefore these alterations may protect South Asians from the development of foot ulceration.