Abstract:Diabetic foot ulcer（DFU）has traditionally been regarded as a localized wound problem, but emerging evidence indicates that it is essentially a focal manifestation of systemic metabolic-inflammatory-immune decompensation. Building upon the “cardio-renal-metabolic-foot” connection, this review further integrates the muscle-nutrition dimension and the psychological-cognitive dimension to systematically elaborate the multisystem hazards of DFU. Patients with DFU have a more than twofold increased risk of cardiovascular death；40%-60% of them have comorbid chronic kidney disease, and declining renal function significantly elevates the risk of amputation. Sarcopenia and malnutrition constitute a double barrier to wound healing, forming a vicious cycle. The incidence of depression in patients with DFU is as high as 47%, and cognitive dysfunction is prevalent, yet these conditions have long been clinically overlooked. These dimensions mutually reinforce each other through mechanisms such as systemic inflammation, oxidative stress, endothelial dysfunction, and reduced behavioral adherence. Clinical management should shift from isolated wound care to multidisciplinary collaboration, with routine integration of sarcopenia assessment, nutritional screening, and psychological-cognitive support. Incorporating the muscle, nutritional, psychological, and cognitive dimensions into the systemic framework of DFU helps to more comprehensively understand the disease burden and optimize individualized treatment strategies.