Diabetic foot syndrome (DFS) is one of the most severe and disabling complications of diabetes mellitus (DM), representing a clinical manifestation of systemic involvement rather than merely a localized foot defect. This literature review highlights global and Russian epidemiology of DFS, emphasizing its central role in the prevalence of non-traumatic amputations and mortality. The key pathogenetic links of DFS include diabetic peripheral neuropathy, chronic hyperglycemia, immune dysfunction, and local biomechanical factors that contribute to the formation of chronic non-healing ulcers. The review also describes the roles of diabetic neuro-osteoarthropathy, musculoskeletal foot alterations, and elevated plantar pressure, alongside skin barrier impairment and disrupted wound healing phases, which account for high rates of infection and amputation.

   Special attention is paid to the impact of comorbidities on the clinical course of DFS; these conditions aggravate the syndrome through mechanisms of systemic inflammation and a prothrombotic state, thereby increasing the risk of major adverse limb events (MALE) and overall mortality.

   Furthermore, genetic and epigenetic factors determining individual predisposition to DFS and variability in ulcer healing are discussed. The therapeutic section presents modern approaches to DFS risk stratification and management principles for diabetic foot ulcers, including the necessity of glucose-lowering therapy and timely revascularization in cases of critical limb ischemia.

   The review emphasizes the need for a multidisciplinary approach and regular foot screening in patients with significant comorbidity to reduce amputation rates and improve quality of life.