An Investigation into the Association Between Skin Microcirculation and Small Fibre Function in the Foot: Potential Implications in Assessing the Cutaneous Neurovascular Response in Diabetic Foot Disease

Diabetes is a global public health problem as it is associated with various complications. One of the major complications of diabetes is diabetic foot syndrome, which leads to catastrophic events such as ulceration and amputation. The triggers of ulcerations are multifactorial, including cutaneous microcirculatory changes in the foot of people with diabetes. The cutaneous microcirculation of the foot is strongly influenced by the small fibres that mediate the sensation of heat and pain, in addition to sympathetic activities such as thermoregulation and vasodilation. However, there is a lack of knowledge on the subject of microcirculation, small fibre nerves, their relationship, evaluation and possible role in ulceration in the context of diabetic foot. This research aimed to investigate the relationship between cutaneous microvascular and small fibre nerve functions in the foot. The review of the existing literature, which was undertaken as a part of this thesis, revealed that there is a relationship between microcirculation and the functions of the small nerve fibres. The first study of this thesis highlighted that the skin microcirculation in the foot can be systematically and reliably assessed with the Post-Occlusive Reactive Hyperaemia (PORH) test with an occlusion time of 30 seconds, which makes the test potentially viable in a clinical setting for diabetic foot assessment. The minimal time occlusion can be safe for people with underlying complications and be easily measured alongside ABI or TBI. This study also confirmed that small fibre nerves play an important role in regulating skin temperature, which affects cutaneous perfusion. It was concluded that there is a strong relationship between cutaneous microcirculation and foot skin temperature. In addition, it was found that the skin temperature is an independent predictor of microcirculation, meaning it can be a surrogate method of assessing microcirculation. In summary, this research has contributed to a thorough understanding of the relationship between microcirculatory and both sensory and autonomic functions of the small fibre nerves and their interdependence. Risk assessment of diabetic foot requires comprehensive assessment as one parameter alone cannot help to understand the foot microclimate and identify a foot at risk. The results of the current thesis contribute to the understanding of soft tissue biomechanics and to help develop strategies for a comprehensive assessment of the diabetic foot using time-efficient methods such as PORH and foot temperature measurement. The findings have clinical implications as simple, non-invasive techniques can be instrumental in determining a foot at risk of ulceration, as temperature changes have been associated with foot complications. Such simple assessment techniques can be used in both high and low resource settings for mass screening or even self-screening of the foot. This, in turn, can aid in the prevention and early detection of ulcers, thereby reducing amputations.