Pathophysiology of Microvascular Disease in Diabetes

Diabetes and its associated complications place an enormous economic burden on public health systems, globally, highlighting the need for early intervention and prevention. Diabetes affects the vascular system through many different pathological mechanisms, including endothelial dysfunction and abnormal neurovascular control. These functional changes in microvascular function have a compounding relationship with structural changes in the cutaneous microcirculation of the diabetic foot. Ultimately, such adverse adaptations in function and structure contribute to the formation of diabetic foot complications such as ulceration and in more severe circumstances, peripheral arterial disease and ischemic ulcers that increase the risk of amputation. In recent decades, several noninvasive imaging techniques and tests of microvascular reactivity have evolved that may have the potential to allow clinicians to predict the risk of foot ulceration more accurately and in those with diabetes, as well as provide the ability to monitor wound healing rates and determine the success of therapeutic interventions. This chapter will summarize these methods used to assess the cutaneous microcirculation while also describing the respective roles of hyperglycemia, insulin resistance, and inflammation in endothelial dysfunction and its complex relationship with neurovascular function.