Peripheral neuropathy and its effects on the diabetic foot

Abstract

This thesis describes a number of studies which explore the hypothesis that endoneurial hypoxia is a major component of the pathogenetic mechanisms of diabetic peripheral neuropathy, and that peripheral neuropathy leads to structural changes in the diabetic foot. Microvascular blood flow and rheology were studied in three age and sex matched groups; diabetic patients with and without neuropathy, and non-diabetic control subjects. Peroneal nerve motor conduction velocity was significantly associated with transcutaneous oxygen tension, r=0.6.p<0.001. No significant differences in rheological parameters were found between non-neuropathic diabetic patients and controls, but significant adverse changes were found in rheological parameters, prostacyclin levels and fibrinolysis, in diabetic patients with neuropathy, in the absence of other complications. Peroneal nerve motor conduction velocity was measured in 10 non-diabetic and 6 diabetic patients before and after unilateral femoro-popliteal bypass surgery to assess the effect of improving tissue blood flow on nerve function. The contralateral leg served as a control. Restoring tissue oxygenation was associated with significant improvements in peroneal conduction velocity in both non-diabetic and diabetic patients, which may suggest new therapeutic strategies for peripheral neuropathy in man. The effects of diabetic neuropathy on the foot were examined by a radiographic survey of the prevalence of bone and soft tissue changes in the feet of diabetic patients and normal controls. This demonstrated that medial arterial calcification is significantly associated with peripheral neuropathy, making the use of ankle pressure indices unreliable in neuropathic patients. It also found an higher than previously recognised prevalence of traumatic and Charcot fractures amongst neuropathic diabetic patients. Further work demonstrated that Charcot patients have a global neurological impairment when compared to matched neuropathic patients without Charcot changes, and significantly reduced bone mineralisation, a possible predisposing factor for the fractures which often initiate the destructive phase of a Charcot joint. Finally, a new treatment for acute Charcot neuroarthropathy, intravenous Pamidronate, was evaluated, and proved effective in reducing the increased bone turnover, swelling and discomfort associated with the Charcot process.