Tang Weiwei, Chen Shengqiu, Zhang Shuxia, Ran Xingwu
Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China.
Innovation Research Center for Diabetic Foot, Diabetic Foot Care Center, West China Hospital of Sichuan University, Chengdu 610041, China.
Int J Mol Sci. 2025 Jun 14;26(12):5719. doi: 10.3390/ijms26125719.
Diabetic foot ulcers (DFUs) constitute a severe and debilitating complication of diabetes, imposing a substantial global health burden due to their intricate pathophysiology and impaired wound healing processes. Vitamin D deficiency is highly prevalent among diabetic populations, and accumulating evidence indicates its potential involvement in the pathogenesis and prognosis of DFUs. This review comprehensively explores the diverse roles of vitamin D in DFUs, encompassing its molecular mechanisms such as immunomodulation, promotion of angiogenesis, neuroprotection, and induction of antimicrobial peptides, as well as the metabolic characteristics associated with various vitamin D forms and compromised vitamin D receptor (VDR) signaling pathways. Although robust observational studies have established an association between vitamin D deficiency and adverse outcomes in DFUs, the clinical validation of supplementation efficacy through randomized controlled trials (RCTs) remains constrained by limitations such as small sample sizes, heterogeneity in study protocols, and insufficient long-term follow-up. This highlights the critical need for large-scale, high-quality studies to ascertain optimal treatment regimens and to cater to individualized patient requirements, particularly for individuals with obesity or those with renal impairments. Innovative strategies, such as the topical administration of vitamin D through intelligent delivery systems leveraging advanced biomaterials like nanofibers and hydrogels, exhibit substantial preclinical potential in enhancing stability, achieving targeted controlled release, and augmenting local biological effects, including the induction of antimicrobial peptides. Nevertheless, significant challenges persist in conclusively establishing clinical efficacy, comprehensively elucidating the underlying mechanisms, ensuring the safe translation of novel delivery systems, and developing personalized therapeutic strategies. The future success of these interventions hinges on meticulous research and interdisciplinary collaboration to seamlessly integrate validated vitamin D-based interventions into a comprehensive multidisciplinary management framework for DFUs, thereby holding promise for improving the clinical outcomes of this debilitating condition.
糖尿病足溃疡（DFUs）是糖尿病一种严重且使人衰弱的并发症，因其复杂的病理生理学和受损的伤口愈合过程，给全球健康带来了沉重负担。维生素D缺乏在糖尿病患者中极为普遍，越来越多的证据表明其可能参与DFUs的发病机制和预后。本综述全面探讨了维生素D在DFUs中的多种作用，包括其免疫调节、促进血管生成、神经保护和诱导抗菌肽等分子机制，以及与各种维生素D形式和受损维生素D受体（VDR）信号通路相关的代谢特征。尽管强有力的观察性研究已证实维生素D缺乏与DFUs不良结局之间存在关联，但通过随机对照试验（RCTs）对补充疗效进行临床验证仍受到样本量小、研究方案异质性和长期随访不足等限制。这凸显了开展大规模、高质量研究以确定最佳治疗方案并满足个体化患者需求的迫切需要，特别是对于肥胖患者或肾功能受损患者。创新策略，如通过利用纳米纤维和水凝胶等先进生物材料的智能递送系统局部应用维生素D，在提高稳定性、实现靶向控释和增强局部生物学效应（包括诱导抗菌肽）方面展现出巨大的临床前潜力。然而，在最终确定临床疗效、全面阐明潜在机制、确保新型递送系统的安全转化以及制定个性化治疗策略方面仍存在重大挑战。这些干预措施未来的成功取决于细致的研究和跨学科合作，以便将经过验证的基于维生素D的干预措施无缝整合到DFUs的综合多学科管理框架中，从而有望改善这种使人衰弱疾病的临床结局。
