**1. Introduction**

Diabetic foot ulceration (DFU) is a serious complication of diabetes mellitus worldwide, and the most common cause of in-patient admissions among the diabetic population [1, 2]. It reduces mobility and quality of life of patients. Left untreated or poorly managed, DFU can lead to amputation, and death in extreme cases [3]. The etiology of DFU is quite complex due to the involvement of a number of pathophysiological mechanisms, with polyneuropathy being the most crucial of them all [4, 5]. Proper adherence to standard treatment strategies (both pharmacological and nonpharmacological) and interdisciplinary cooperation between healthcare practitioners (doctors, nurses, pharmacists, etc.) and the patient can reduce the relatively high rates of major amputations and mortality in diabetic patients due to DFU [6–8].

Diabetes-related foot complications have been identified as the most common cause of morbidity among diabetic patients [1]. Peripheral vascular disease is a major underlying risk factor for the development of DFU due to reduced oxygenation of the foot. It renders the diabetic foot asymptomatic until latter evidence of non-healing ulcers become evident [9, 10]. Also, uremia due to diabetic kidney disease (DKD) reduces the body's immune capabilities and creates a suitable environment for bacterial growth in the foot ulcers [11]. Inadequate oxygenation or perfusion of the affected foot aids in the progression of DFU due to a reduced delivery of antibiotics to the affected foot. At this point, the patient needs to be monitored strictly to prevent the steady progression of DFU to diabetic gangrene, a condition where foot ulcerations become necrotic and unresponsive to antibiotic therapy and ultimately may require amputation of the affected foot [12, 13].

While about 6.3% of patients currently have foot ulcerations worldwide [14], it is estimated that about 25% of diabetic patients may develop DFU in their lifetime [5]. Of all amputations in diabetic patients, 85% are preceded by DFU, which subsequently worsens to a gangrene or infection [3, 15]. DFU is more prevalent in type 2 diabetic patients, with these patients suffering recurring hospital admissions which increases their financial burden on the healthcare system and the patient [16]. Everett and Mathioudakis [17] recently reported that diabetic patients with DFU have 2.5 times increase of dying while experiencing an 11-fold increase in hospital costs compared to patients hospitalized for nondiabetic foot ulcer. A patient's likelihood of developing DFU increases as his or her disease duration increases [18], while complications such as DKD further increases the patient's risk of getting foot ulcers [19]. Furthermore, the severity of DFU delays wound healing time [18, 20], which consequently increases the cost of its clinical management. This chapter discusses the causal pathways in DFU development and progression, the relationship between DKD and DFU as well as treatment options and measures to achieve both primary and secondary prevention.
