https://doi.org/10.1177/1534734620944514 The International Journal of Lower Extremity Wounds 1–9 © The Author(s) 2020 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1534734620944514 journals.sagepub.com/home/ijl Original Article Understanding Diabetic Foot Ulcers: Past and Present Diabetic foot ulcers (DFU) represent a major public health concern. In the United Kingdom, the incidence of foot ulcers among patients with diabetes was found to be 2.2%, 1 while in the global population the incidence may be as high as 6.3%. 2-4 DFU carry significant morbidity and mortality risk as the risk of death at 5 years is 2.5 times higher in diabetic patients with DFU than in diabetic patients with- out DFU. 5 Furthermore, diabetes increases the incidence of foot ulcer admissions by 11-fold, accounting for more than 80% of all amputations and 10-fold increased hospital costs estimated over 5 years. 6 Thus, the pathogenesis of DFU requires elucidation in order to address this signifi- cant public health issue. The earliest descriptions of DFU date back to the 19th century when gangrene of the foot was first associ- ated with diabetes. At that time, these ulcers were described as “gangrene in the diabetic foot” or “diabetic gangrene” and treatment consisted of prolonged bed rest. For many years, this terminology, which emphasized ischemia and infection, hindered the correct management of DFU as it ignored an important contributor to dis- ease—neuropathy. It was not until the 1950s that neu- ropathy was incorporated into the classification of DFU and the more encompassing terms “diabetic foot” and “diabetic ulcers” became popular, allowing for a better understanding of these wounds. 7 Since then, several terms have been used to describe the unique foot ulcers that occur in diabetes. They include “neuropathic foot ulcer” and most recently “diabetic foot ulcer,” which may be most appropriate since it suggests various patho- logical mechanisms, instead of a single disease process. This review aims to summarize the various mechanisms that contribute to DFU in order to reappraise clinicians’ understanding of these wounds. Pathways leading to DFU are many and include neuropathy, vascular disease, and 944514IJL XX X 10.1177/1534734620944514The International Journal of Lower Extremity WoundsAldana et al research-article 2020 1 University of Maryland, Baltimore, MD, USA 2 Veterans Affairs Medical Center, Brooklyn, NY, USA 3 SUNY Downstate, Brooklyn, NY, USA Corresponding Author: Amor Khachemoune, Veterans Affairs Hospital Dermatology Service, 800 Poly Place, Brooklyn, NY 11209, USA. Email: amorkh@gmail.com Reappraising Diabetic Foot Ulcers: A Focus on Mechanisms of Ulceration and Clinical Evaluation Paola C. Aldana, MD 1 , Alexander M. Cartron, BS 1 , and Amor Khachemoune, MD, FAAD, FACMS 2,3 Abstract 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. Keywords diabetic foot ulcers, peripheral neuropathy, vascular, wound infection