关键词: 糖尿病足, 溃疡, 血管生成, 脂肪组织, 脂肪因子, 胰岛素抵抗, 脂肪源性干细胞, 外泌体, 治疗策略

Abstract: Diabetic foot ulcer (DFU) represents one of the most severe and devastating chronic complications of diabetes mellitus, imposing a substantial burden on health care systems worldwide. The refractory nature of DFU stems from its characterization not merely as a localized lesion, but as a local manifestation of systemic metabolic dysregulation. This review systematically examines the pivotal roles of impaired angiogenesis and adipose tissue metabolic remodeling—two interrelated core pathologic processes—in the nonhealing phenotype of DFU and explores their intricate interdependence.In the diabetic state, hyperglycemia-induced toxicity, accumulation of advanced glycation end products, and dysregulation of growth factor signaling cascades collectively impair local neovascularization. These abnormalities manifest as endothelial progenitor cell dysfunction, an imbalance between proangiogenic and antiangiogenic factors, and extracellular matrix remodeling dyshomeostasis. Concurrently, adipose tissue undergoes pathologic remodeling characterized by adipocyte hypertrophy, chronic low-grade inflammation, and an altered adipokine secretory profile, thereby establishing a systemic proinflammatory milieu through the release of inflammatory mediators and free fatty acids.These two pathogenic mechanisms do not operate independently but are intimately linked through an "adipose-vascular axis." Adipose tissue inflammation exacerbates endothelial dysfunction and impairs angiogenesis, while compromised local perfusion further aggravates adipose tissue hypoxia and functional derangement, thereby perpetuating a vicious cycle. This interconnected pathology ultimately culminates in persistent wound inflammation, impaired cellular energy metabolism in reparative cells, and arrested healing progression.Based on these mechanistic insights, this review evaluates multimodal therapeutic strategies targeting this pathogenic cycle, including systemic interventions that ameliorate adipose tissue dysfunction at its source and localized approaches that promote vascular regeneration. Future directions should focus on integrating systemic metabolic modulation with regional regenerative medicine through multi-targeted, personalized combination regimens, potentially overcoming current therapeutic limitations and offering novel pathways for DFU healing.

Key words: Diabetic foot, Ulcer, Angiogenesis, Adipose tissue, Adipokines, Insulin resistance, Adipose-derived stem cells, Exosomes, Therapeutic strategies