An aging population and changes in dietary habits have increased the incidence of diabetes, resulting in complications such as diabetic foot ulcers (DFUs). DFUs can lead to serious disabilities, substantial reductions in patient quality of life, and high financial costs for society. By understanding the etiology and pathophysiology of DFUs, their occurrence can be prevented and managed more effectively. The pathophysiology of DFUs involves metabolic dysfunction, diabetic immunopathy, diabetic neuropathy, and angiopathy. The processes by which hyperglycemia causes peripheral nerve damage are related to adenosine triphosphate deficiency, the polyol pathway, oxidative stress, protein kinase C activity, and proinflammatory processes. In the context of hyperglycemia, the suppression of endothelial nitric oxide production leads to microcirculation atherosclerosis, heightened inflammation, and abnormal intimal growth. Diabetic neuropathy involves sensory, motor, and autonomic neuropathies. The interaction between these neuropathies forms a callus that leads to subcutaneous hemorrhage and skin ulcers. Hyperglycemia causes peripheral vascular changes that result in endothelial cell dysfunction and decreased vasodilator secretion, leading to ischemia. The interplay among these four preceding pathophysiological factors fosters the development and progression of infections in individuals with diabetes. Charcot neuroarthropathy is a chronic and progressive degenerative arthropathy characterized by heightened blood flow, increased calcium dissolution, and repeated minor trauma to insensate joints. Directly and comprehensively addressing the pathogenesis of DFUs could pave the way for the development of innovative treatment approaches with the potential to avoid the most serious complications, including major amputations.
Citations
Citations to this article as recorded by
Exploration of recent advancements of nanoparticle-based therapeutics emphasis on diabetic-related chronic wound management: a comprehensive review Esraa M. Elshazly, Mona G. Arafa, Samia A. Nour Archives of Pharmacal Research.2026; 49(1): 101. CrossRef
Wireless, Battery‐Free, Optoelectronic, Multi‐Modal Sensor Integrated With Colorimetric Dressing for Diabetic Ulcer Management Seokjoo Cho, Ji‐Hwan Ha, Jiwon Moon, Jihyeon Ahn, Gwangmook Kim, Xiaotian Ma, Kexin Fan, Ruihao Song, Donho Lee, Hyeonseok Han, Junseong Ahn, Youngwoo Oh, Wooyeol Choi, Yong Suk Oh, Soonhyoung Hwang, Sohee Jeon, Yongrok Jeong, Dahong Kim, Su A. Park, Jun‐ Advanced Functional Materials.2026;[Epub] CrossRef
A Dual-Network Injectable Hydrogel Scaffold Integrating Glycyrrhizic Acid and Acellular Fat Extracts for Synergistic Enhancement of Diabetic Wound Healing Qiang Jin, Miao-Yun Jiang, Li-Li Wang, Shi-Qi Lin, Ting Li, Ze-Xin Fu, Lei Zhang, Su-Fan Wu, Yi Sun ACS Polymers Au.2026; 6(1): 164. CrossRef
Circular RNAs in Diabetic Foot Ulcers: A Scoping Review of Clinical, Preclinical, and In Silico Evidence on Diagnostic and Therapeutic Potentials Amir Reza Ghafourian, Masoomeh Hamdi, Atefeh Soltan Mohseni, Maryam Davoudi, Hamid Choobineh, Fariba Nabatchian, Reza Afrisham Endocrinology, Diabetes & Metabolism.2026;[Epub] CrossRef
Global prevalence of diabetes-related neuropathy and vascular complications: A systematic review and meta-analysis Asmat Burhan, Ramida Subpaiboonkit, Hui-Chuan Huang Diabetes Research and Clinical Practice.2026; 232: 113103. CrossRef
The Interplay Between Nurr1 and Mitochondrial Biogenesis: Implications for Neurodegenerative Therapy Simranjeet Kaur, Ashi Mannan, Thakur Gurjeet Singh Molecular Neurobiology.2026;[Epub] CrossRef
Evaluation of Tibial Nerve Microcirculation in Diabetes Mellitus at Superresolution US Fang Liu, ShuJun Xia, Qing Hua, CongCong Yuan, YuHang Zheng, RuoLin Tao, JiaLe Xu, YuLu Zhang, FangGang Wu, Wei Guo, Yuan Tian, YiJie Dong, JianQiao Zhou Radiology.2026;[Epub] CrossRef
An off-the-shelf bioactive EV delivering cryogel orchestrating immunomodulatory reprogramming and angiogenesis for diabetic ulcer healing Parvaiz Ahmad Shiekh, Ubaid Tariq, Durga Nandini Athmuri, Prerna Singh, Jayanta Bhattacharyya, Ashok Kumar, Naresh Bhatnagar Biomaterials.2026; 330: 124053. CrossRef
Responsive to adaptive supramolecular hydrogels for diabetic wound treatment Shalini Balakrishnan, Revathy Remesh, Krishnan Kartha Kalathil, Anie Y Supramolecular Materials.2025; 4: 100081. CrossRef
Nanotechnology-enabled approaches for combating diabetic foot ulcer Padakanti Sandeep Chary, Anuradha Urati, Samia Shaikh, Rati Yadav, Valmala Bhavana, Naveen Rajana, Neelesh Kumar Mehra Journal of Drug Delivery Science and Technology.2025; 105: 106593. CrossRef
Natural products in the treatment of diabetic foot infection Mohsen Nazari, Leili Shokoohizadeh, Mohammad Taheri European Journal of Medical Research.2025;[Epub] CrossRef
Comprehensive review on diabetic foot ulcers and neuropathy: Treatment, prevention and management Kehkashan Parveen, Malik Asif Hussain, Sadaf Anwar, Halima Mustafa Elagib, Mohd Adnan Kausar World Journal of Diabetes.2025;[Epub] CrossRef
Enhanced therapy for diabetic neuropathy utilizing venlafaxine hydrochloride-loaded transferosome-based transdermal gel Kajol Patil, Pramod S. Salve, Ujban Md Hussain Hussain, Amol Tatode, Mohammad Qutub Nano Trends.2025; 9: 100085. CrossRef
Antioxidants improve the viability of diabetic bone marrow MSCs without rescuing their pro-regenerative secretome function Michelle Maartens, Mare Vlok, Mari van de Vyver Molecular and Cellular Endocrinology.2025; 601: 112519. CrossRef
Risk Factors Associated with Diabetic Foot Ulcers: A Multivariate Analysis Ajeet Saoji, Nitesh Upadhyay, Prachi Saoji, Kartik Khurana Biomedical and Biotechnology Research Journal.2025; 9(1): 67. CrossRef
Bacteriological profile of diabetic foot ulcers and analysis of serum meteorin levels Esra Erdogan, Azize Yetisgen, Lezzan Keskin, Elif Seren Tanriverdi, Isilay Gokce Benk Ugur Molecular Biology Reports.2025;[Epub] CrossRef
DFU-FuzzyLiteUNet: A lightweight u-net with Fuzzy sigmoid and lite transformer for diabetic foot ulcer segmentation Purwono Purwono, Yessica Nataliani, Hindriyanto Dwi Purnomo, Ivanna K. Timotius Biomedical Signal Processing and Control.2025; 108: 107902. CrossRef
Outcome of diabetic foot ulcers at a Tertiary Care Foot Centre in Pakistan Zahid Miyan, Arwa Hatim, Saniya Khakwani, Khalid Abdul Basit International Wound Journal.2025;[Epub] CrossRef
Diabetic Foot Ulcers: Pathophysiology, Immune Dysregulation, and Emerging Therapeutic Strategies John Dawi, Kevin Tumanyan, Kirakos Tomas, Yura Misakyan, Areg Gargaloyan, Edgar Gonzalez, Mary Hammi, Serly Tomas, Vishwanath Venketaraman Biomedicines.2025; 13(5): 1076. CrossRef
Adipose-derived Stem Cells for Treatment of Diabetic Foot Ulcers: A Review Prithiviraj Nagarajan, Rajalaksmi Prithiviraj, Sharangouda J. Patil, Suresh Babu Naidu Krishna, Vasanthrie Naidoo Current Stem Cell Research & Therapy.2025; 20(5): 509. CrossRef
The gel effect: Enhancing diabetic foot ulcer healing through hydrogel innovations Ghadeer Almarzooq, Ahmed Alaysereen, Zain Salman, Zahra Abdulrasool, Noor Jaragh, Sara Hasan, Omer Tarig, G. Roshan Deen BME Horizon.2025;[Epub] CrossRef
The combined impact of thymosin beta 4 and selenium on diabetic ulcers: a comprehensive review Karthikeyen Srinivasan, Rohith Sureshkumar, Jayshree Nellore, Bavanilatha Muthaiah, Johnson Retnara Samuel Selvan Christyraj, Valli Nachiyar Chandrasekaran Discover Biotechnology.2025;[Epub] CrossRef
Epigenetics and diabetic wound healing: Wilms tumor 1-associated protein as a therapeutic target Ashraf Al Madhoun World Journal of Diabetes.2025;[Epub] CrossRef
Synergistic Effect of Prolonged Oxygenation and Reactive Oxygen Species Scavenging on Diabetic Wound Healing Using an Injectable Thermoresponsive Hydrogel Jiyeon Lee, Jun Kim, Jisun kim, Soo‐Chang Song Small.2025;[Epub] CrossRef
Dysfunction of Microcirculation in Atherosclerosis: Implications of Nitric Oxide, Oxidative Stress, and Inflammation Marta Aleksandrowicz, Marek Konop, Mateusz Rybka, Łukasz Mazurek, Monika Stradczuk-Mazurek, Mateusz Kciuk, Bożena Bądzyńska, Leszek Dobrowolski, Marta Kuczeriszka International Journal of Molecular Sciences.2025; 26(13): 6467. CrossRef
Role of PPARγ, IL-1β Blockers, and TGF-β1 in Diabetic Wound Healing: Mechanisms and Therapeutic Potential Riani Erna, Arief S. Kartasasmita, Shanti F. Boesoirie, Wijana Hasansulama, Ramzi Amin Journal of Wound Management and Research.2025; 21(2): 58. CrossRef
From Control to Cure: Insights into the Synergy of Glycemic and Antibiotic Management in Modulating the Severity and Outcomes of Diabetic Foot Ulcers Idris Ajibola Omotosho, Noorasyikin Shamsuddin, Hasniza Zaman Huri, Wei Lim Chong, Inayat Ur Rehman International Journal of Molecular Sciences.2025; 26(14): 6909. CrossRef
In silico based Diabetic Wound Healer from Nature: An Update Amit Lather, Pratibha Rathee, Manish Kumar Gautam, Kalicharan Sharma, Tanuj Hooda Current Drug Discovery Technologies.2025;[Epub] CrossRef
After the Foot has Healed Mark Mendeszoon, Ewald Mendeszoon, Hayley Iosue Clinics in Podiatric Medicine and Surgery.2025; 42(4): 767. CrossRef
Clinical Evaluation of Diabetic Foot Ulcers Using the SINBAD (Site, Ischemia, Neuropathy, Bacterial Infection, Area, and Depth) Scoring System: A Prospective Study Hrudaya Charan Kunda, Madhu A Yadav, Tanissha Sanjay Raj Kalpana, Dhrushti Premal Patel, Sivanandhini Sivanoli, Naman Dimpal Shah, Shahista Shahista, Jitenkumar Panchal Cureus.2025;[Epub] CrossRef
Microvascular, Biochemical, and Clinical Impact of Hyperbaric Oxygen Therapy in Recalcitrant Diabetic Foot Ulcers Daniela Martins-Mendes, Raquel Costa, Ilda Rodrigues, Óscar Camacho, Pedro Barata Coelho, Vítor Paixão-Dias, Carla Luís, Ana Cláudia Pereira, Rúben Fernandes, Jorge Lima, Raquel Soares Cells.2025; 14(15): 1196. CrossRef
Battery-free, sprayable, wireless photothermal micro/nanofibre dressing with thermal-induced crosslinked polypyrrole for accelerated diabetic wound healing Chun-Chi Chang, Ting-Chiau Huang, Jia-Wei Liang, Sih-Chi Chuang, Ching-Cheng Huang, Hieu Trung Nguyen, Hsien-Tsung Lu, Ke-Hung Tsui, Andrew E.-Y. Chuang Journal of Drug Delivery Science and Technology.2025; 114: 107392. CrossRef
Progressive Hydrogel Applications in Diabetic Foot Ulcer Management: Phase-Dependent Healing Strategies Priyanka Mallanagoudra, Sai Samanvitha M Ramakrishna, Sowmya Jaiswal, Dhruthi Keshava Prasanna, Rithika Seetharaman, Arunkumar Palaniappan, Sudarshan Kini Polymers.2025; 17(17): 2303. CrossRef
Exploring the Role of GLP‐1 Agents in Managing Diabetic Foot Ulcers: A Narrative and Systematic Review Fiona S. Gruzmark, Gabriela E. Beraja, Ivan Jozic, Hadar A. Lev‐Tov Wound Repair and Regeneration.2025;[Epub] CrossRef
An Assessment of Diabetes-Dependent Quality of Life in Polish Patients Ewelina Bąk, Grzegorz Zawiła, Robert Skalik, Sylwia Krzemińska, Bogusława Kupczak-Wiśniowska, Lukas Kober, Elena Gurková Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 3387. CrossRef
A review of the basic science of the diabetic foot and its complications Catherine Flood, David Okata, Valliammai Muthuganesan, Chi Fung Antony Yiu, Stephen Bendall Orthopaedics and Trauma.2025; 39(5): 276. CrossRef
Challenges and Solutions in Advanced Management of Diabetic Foot Infections: A Review of Recent Studies Somaye Rashki, Mohammad Hossein Haddadi, Zeynab Marzhoseyni, Mansoor Khaledi, Mina Yekani, Mahdi Shooraj, Foroogh Neamati, Richard Bright Journal of Diabetes Research.2025;[Epub] CrossRef
Screening and monitoring of diabetic polyneuropathy in clinical practice: present and future with connected devices Jean-Pascal Lefaucheur Frontiers in Neurology.2025;[Epub] CrossRef
Hinged total knee arthroplasty in two female patients with type 1 diabetes-associated charcot neuroarthropathy: case reports and a review of the literature series Chao Lei, Wen-zhou Huang, Lin Mei, Kuo Sun, Xin-zhan Mao BMC Musculoskeletal Disorders.2025;[Epub] CrossRef
Modeling heterogeneity of diabetic foot self-care behaviors in Al Qassim Region in Saudi Arabia Reem Alsalamah Journal of Medicine and Life.2025; 18(9): 893. CrossRef
Genetic polymorphisms and diabetic foot ulcer susceptibility: a systematic review and meta-analysis of Indian populations Y. Santhosh Kumar, A. Saroja Megha, M. Ramula, Murugesan Ramachandran Journal of Diabetes & Metabolic Disorders.2025;[Epub] CrossRef
Advances in diabetic wound healing: from pathophysiology to emerging therapies Swati Swagatika Swain, Veera Venkata Satyanarayana Reddy Karri, Md Ekhtiar Uddin, Kuppuswamy Gowthamarajan, Manimaran Bhaskaran, Vetriselvan Subramaniyan Acta Diabetologica.2025;[Epub] CrossRef
Monitoring of IL-1β and MCP-1 Levels in Diabetic Patients with Foot Ulcer Infections Mays Ibrahim Al-Wakeel Academia Open.2025;[Epub] CrossRef
A personalized approach to the treatment and prevention of diabetic foot: molecular mechanisms and the role of taxifolin P.V. Seliverstov, V.V. Zakrevsky, A.S. Ivaniuk, А.М. Kerimova, S.E. Maltsev, K.M. Tokarev Molekulyarnaya Meditsina (Molecular medicine).2025; : 30. CrossRef
Diabetic foot – prevention and control challenges Vitorino Modesto dos Santos, Taciana Arruda Modesto Sugai, Lister Arruda Modesto dos Santos Belize Journal of Medicine.2024;[Epub] CrossRef
Treatment of Morganella morganii-Associated Non-healing Diabetic Foot Ulcer With Vaporous Hyperoxia Therapy: A Case Report Afrah S Abedi, Jacob L McElroy, Vladimir Valencia, Rachel M Worcester, Zhi J Yu Cureus.2024;[Epub] CrossRef
Integrated genetic analysis of diabetic complications: Bioinformatics insights into foot ulcers, neuropathy and peripheral artery disease Jiaru Liang, Xiaoyang Gong, Xuyang Hu, Chong You, Jiaqi Zhou, Yuling Gao, Junwei Zong, Yong Liu International Wound Journal.2024;[Epub] CrossRef
Systematic review of translational insights: Neuromodulation in animal models for Diabetic Peripheral Neuropathy Rahul Mittal, Keelin McKenna, Grant Keith, Evan McKenna, Rahul Sinha, Joana R. N. Lemos, Khemraj Hirani, Mohammad Sarif Mohiuddin PLOS ONE.2024; 19(8): e0308556. CrossRef
Effect of Treatment of Neuropathic and Ischemic Diabetic Foot Ulcers with the Use of Local Ozone Therapy Procedures—An Observational Single Center Study Jarosław Pasek, Sebastian Szajkowski, Grzegorz Cieślar Clinics and Practice.2024; 14(5): 2139. CrossRef
High glucose combined with lipopolysaccharide stimulation inhibits cell proliferation and migration of human HaCaT keratinocytes by impacting redox homeostasis and activating the polyol pathway Zhenhui Xie, Shufan Zhou, Songtao Tang, Qiu Zhang, Lei Liu Molecular Biology Reports.2024;[Epub] CrossRef
Unveiling the challenges of diabetic foot infections: diagnosis, pathogenesis, treatment, and rehabilitation Chul Hyun Park Journal of Yeungnam Medical Science.2023; 40(4): 319. CrossRef