Bhamidipati Theja, Hajj John P, Ghoneim Nehal I, Pradhan Arhat M, Mishra Sanjay, Gummalla Bharat, Abouhashem Ahmed Safwat, Parmar Avanish Singh, Khanna Savita, Roy Sashwati, Sen Chandan K, Singh Kanhaiya
Division of Vascular Surgery, Jefferson Einstein Health, East Norriton, Pennsylvania, USA.
Indiana University School of Medicine, Indianapolis, Indiana, USA.
Adv Wound Care (New Rochelle). 2025 Aug 13. doi: 10.1177/21621918251366681.
Skin lipids are essential for various skin functions including maintaining barrier integrity, regulating hydration, and providing protection against microbes and inflammatory irritants. Along with skin health, the role of lipids in the etiology of macroangiopathic diseases, such as atherosclerosis of arteries, is well recognized. In diabetes, lipid dysregulation is evident and may contribute to the diverse complications of the disease. Diabetic vasculopathy primarily reflects the dysfunction and deterioration of existing blood vessels, as their preservation is key in preventing the progression of vascular disease and reducing the need for compensatory angiogenesis. In the peripheral diabetic skin of the limbs, diabetic vasculopathy runs alongside peripheral neuropathy. Although a causative link between the two is plausible, direct evidence in support of such claim is scanty. Diabetic skin is known to be compromised in many ways, including weakened barrier functionality and diabetes-induced alterations in the extracellular matrix, likely stemming from chronic inflammation, which may directly affect vascular integrity and nerve health. Both, in the compromised skin and within wounds, microbial pathogens and their enzymes may metabolize host lipids, driving inflammatory reactions and exacerbating the pathogenesis of diabetic vasculopathy and related neuropathy. This review focuses on lipid mediators such as sphingolipids, resolvins, oxidized low-density lipoproteins and their specific downstream signaling pathways to obtain a comprehensive understanding of diabetic complications relevant to wound healing. Through lipid-based strategies, this review hopes to inspire the development and utilization of individualized, precision-based approaches to manage diabetic vasculopathy and neuropathy.
皮肤脂质对多种皮肤功能至关重要，包括维持屏障完整性、调节水合作用以及抵御微生物和炎性刺激物。除了对皮肤健康的作用外，脂质在大血管病变疾病（如动脉粥样硬化）的病因学中的作用也已得到充分认识。在糖尿病中，脂质失调很明显，可能导致该疾病的各种并发症。糖尿病血管病变主要反映现有血管的功能障碍和恶化，因为保持血管功能对于预防血管疾病进展和减少代偿性血管生成的需求至关重要。在糖尿病患者四肢的外周皮肤中，糖尿病血管病变与外周神经病变同时存在。尽管两者之间存在因果关系看似合理，但支持这一说法的直接证据却很少。已知糖尿病皮肤在许多方面受到损害，包括屏障功能减弱以及糖尿病引起的细胞外基质改变，这可能源于慢性炎症，而慢性炎症可能直接影响血管完整性和神经健康。在受损皮肤和伤口内，微生物病原体及其酶可能代谢宿主脂质，引发炎症反应，加剧糖尿病血管病变和相关神经病变的发病机制。本综述重点关注鞘脂、消退素、氧化型低密度脂蛋白等脂质介质及其特定的下游信号通路，以全面了解与伤口愈合相关的糖尿病并发症。通过基于脂质的策略，本综述希望激发个性化、精准化方法的开发和应用，以管理糖尿病血管病变和神经病变。
