Reappraising Diabetic Foot Ulcers: A Focus on Mechanisms of Ulceration and Clinical Evaluation.

Diabetic foot ulcers (DFU) are one of the most devastating complications of diabetes as they have significant effects on patient morbidity and mortality. Since their first description in the 19th century, our understanding of DFU has evolved as we uncover the mechanisms that mediate ulceration. In this review, we aim to summarize the various pathways that lead to the development of DFU in order to reappraise physicians' understanding of these complex wounds. Relevant pathways include the following: (1) neuropathy (motor neuropathy, loss of protective sensation, and autonomic sympathetic dysfunction), (2) vascular disease (arterial ischemia, venous insufficiency, and microvascular changes), and (3) metabolism (signaling and immunological effects of hyperglycemia). We also discuss the clinical presentation of DFU and an evidence-based evaluation to assist clinicians in early identification and classification of these wounds to inform management of DFU. Finally, we summarize complications of DFU caused by the various pathways mediating ulceration and briefly overview DFU management in order to educate physicians about the potential risks if left untreated. A better understanding of the synergistic pathways leading to DFU is essential for clinicians to improve DFU diagnosis, tailor intervention, and mitigate significant patient morbidity and mortality.