Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (597 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Common foot problems in persons with diabetes mellitus, caused by any combination of factors such as diabetic neuropathies; peripheral vascular diseases; and infection. With the loss of sensation and poor circulation, injuries and infections often lead to severe foot ulceration, gangrene and amputation, surgical.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Foot, Diabetic; Diabetic Feet; Feet, Diabetic; Foot Ulcer, Diabetic.
Where it fits in the MeSH classification
- Broader topics
- Diabetic Angiopathies; Foot Ulcer; Diabetic Neuropathies
Related concepts
- Diabetes Mellitus
- Diabetic Neuropathies
- Peripheral Vascular Diseases
- Infections
- Gangrene
- Amputation
- Surgical
Research landscape
PubMed indexes 14,545 records tagged with the MeSH heading “Diabetic Foot” (counts retrieved 2026-10-29). 5,701 of them (39.2%) were published from 2020 onward, and the busiest period so far is 2020 onward with 5,701 records.
Reviews account for 3,223 records (22.2%) and meta-analyses for 425. Randomized controlled trials number 792 (5.4%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 1,042 |
| 2000-2009 | 3,013 |
| 2010-2019 | 4,789 |
| 2020 onward | 5,701 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 3,223 | 22.2% |
| Meta-analyses | 425 | 2.9% |
| Randomized controlled trials | 792 | 5.4% |
Method: PubMed query "Diabetic Foot"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in cardiovascular medicine
Cardiovascular medicine has an unusually large body of randomized trials, so the type of outcome matters: hard clinical events such as death, heart attack and stroke carry more weight than changes in blood pressure, cholesterol or imaging markers that only predict risk. Observational studies can show associations but are confounded by age, lifestyle and other illness. Check whether a result is about prevention or treatment, the baseline risk of participants, and the absolute rather than only the relative size of any benefit.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Insights Into Macrophage Polarization and M1/M2 Balance in Diabetic Foot Ulcers | 2026 | Review article Design not recorded in structured metadata | 8 | cc by PMID 41813253 · DOI · PMC12978988 |
| Comprehensive Review of Hydrogel-Mediated Strategies for Diabetic Wound Healing | 2026 | Review article Design not recorded in structured metadata | 5 | cc by PMID 42123497 · DOI · PMC13163982 |
| Comprehensive transcriptomic profiling reveals tissue-specific molecular signatures and dysregulated pathways in human diabetic foot ulcers | 2025 | Research article Design not recorded in structured metadata | 4 | cc by PMID 41255536 · DOI · PMC12620202 |
Insights Into Macrophage Polarization and M1/M2 Balance in Diabetic Foot Ulcers [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Macrophage polarization, encompassing classically activated (M1) and alternatively activated (M2) states, is a critical determinant of immune response in wound healing.
- Closing excerpt
- By integrating mechanistic insights with therapeutic potential, this review provides an updated framework for developing targeted immunomodulatory therapies to break the cycle of non-healing in DFUs.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (144 words)
Macrophage polarization, encompassing classically activated (M1) and alternatively activated (M2) states, is a critical determinant of immune response in wound healing. In diabetic foot ulcers (DFUs), a persistent imbalance favoring pro-inflammatory M1 over anti-inflammatory M2 macrophages drives chronic inflammation and impedes tissue repair. This review delineates the central role of macrophage polarization in DFU pathogenesis and systematically summarizes the key signaling pathways that govern this process, including PI3K/AKT, PPARγ, Notch, and Toll-like receptors (TLRs). We further synthesize these cascades into a novel hierarchical network model, identifying NF-κB and JAK-STAT as the core regulatory hubs. Beyond mechanism, we discuss emerging therapeutic strategies-including pharmacological agents and biomaterial-based approaches-that target macrophage polarization, positioning them as promising adjuvants to standard wound care. By integrating mechanistic insights with therapeutic potential, this review provides an updated framework for developing targeted immunomodulatory therapies to break the cycle of non-healing in DFUs.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41813253 · DOI · PMC12978988
Comprehensive Review of Hydrogel-Mediated Strategies for Diabetic Wound Healing [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Diabetic chronic wounds (particularly diabetic foot ulcers) are difficult to heal due to factors such as high glucose levels, infection, and inflammatory imbalance.
- Closing excerpt
- They offer a multi-pronged approach to disrupt the vicious cycle of "infection-inflammation-tissue destruction" thereby achieving more efficient wound healing.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (257 words)
Diabetic chronic wounds (particularly diabetic foot ulcers) are difficult to heal due to factors such as high glucose levels, infection, and inflammatory imbalance. In severe cases, they can lead to tissue necrosis and amputation. Hydrogel materials, as moist wound dressings, possess high water content, biocompatibility, and tunability, making them an important platform for promoting diabetic wound healing. In recent years, novel smart hydrogels have been developed to integrate multiple functions. They respond to abnormal stimuli in the wound microenvironment-such as acidic pH, high glucose levels, or excessive reactive oxygen species-to trigger the release of drugs, delivering on-demand antimicrobial, antioxidant, and anti-inflammatory effects. Simultaneously, they modulate immune responses (promoting macrophage polarization toward the M2 type) and stimulate angiogenesis, creating a microenvironment conducive to tissue regeneration. Some hydrogels incorporate antimicrobial agents, anti-biofilm components, or photothermal/photodynamic agents to effectively eliminate drug-resistant pathogens and control infections. Others serve as carriers for delivering stem cells and their exosomes, enhancing cell survival rates and releasing growth factors to accelerate wound healing. This review systematically summarizes recent advances in hydrogel strategies for diabetic wound treatment, focusing on stimulus-responsive hydrogels, antimicrobial and immune modulation mechanisms, pro-angiogenic and oxygen-supplying therapies, smart dressings and monitoring technologies, integration of stem cells and exosomes, as well as hydrogel injection, self-healing, and adhesion properties. Based on this, we analyze challenges and prospects for clinical translation of these strategies. Collectively, functionalized hydrogels hold promise as multifunctional therapeutic platforms for diabetic non-healing wounds. They offer a multi-pronged approach to disrupt the vicious cycle of "infection-inflammation-tissue destruction" thereby achieving more efficient wound healing.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42123497 · DOI · PMC13163982
Comprehensive transcriptomic profiling reveals tissue-specific molecular signatures and dysregulated pathways in human diabetic foot ulcers [3]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundDiabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus characterized by impaired wound healing, chronic inflammation, and tissue degeneration.
- Closing excerpt
- Key targets such as chemokine signaling, PPAR-mediated metabolism, and senescence factors emerge as promising candidates for precision therapies aimed at restoring inflammatory-metabolic balance and enhancing wound healing.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (196 words)
BackgroundDiabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus characterized by impaired wound healing, chronic inflammation, and tissue degeneration. We sought to identify tissue specific molecular drivers of DFU pathogenesis across skin, adipose, and muscle compartments.MethodsHigh throughput RNA sequencing was performed on skin, adipose, and muscle tissues from DFU patients and non-ulcerated diabetic controls. Differential expression analyses and pathway enrichment were conducted to delineate common and compartment-specific transcriptional changes.ResultsAll DFU tissues exhibited a conserved upregulation of immune activation genes-including chemokines (CXCL1-8), cytokines (IL1B, IL6), and NF-κB pathway components-alongside downregulation of metabolic regulators (PPARG, ADIPOQ), oxidative phosphorylation genes (SDHA, NDUFS2), and insulin signaling factors (IRS1, AKT2). Skin showed increased keratinocyte proliferation and senescence markers (KRT16, FOXM1); adipose tissue revealed adipocyte dedifferentiation and elevated matrix protease activity (MMP9); and muscle displayed fibrotic remodeling and mitochondrial suppression (COL1A1, NDUFS7). Enrichment analyses implicated IL17 signaling, PPAR pathways, and cellular senescence as central disrupted processes.ConclusionDFUs are driven by a dual pathology of inflammatory amplification and metabolic shutdown, overlaid with distinct tissue-specific alterations. Key targets such as chemokine signaling, PPAR-mediated metabolism, and senescence factors emerge as promising candidates for precision therapies aimed at restoring inflammatory-metabolic balance and enhancing wound healing.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41255536 · DOI · PMC12620202
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis † [4]
- Research article Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis [5]
- Research article Global mortality of diabetic foot ulcer: A systematic review and meta-analysis of observational studies [6]
- Research article The microbiology of diabetic foot infections: a meta-analysis [7]
- Research article Autologous platelet-rich plasma for treating chronic wounds [8]
- Research article Risk factors for lower extremity amputation in patients with diabetic foot ulcers: A meta-analysis [9]
References
- Zhang J, Li H, Dong Y, Zhou Z, Wang Y, Chen X, et al.. Insights Into Macrophage Polarization and M1/M2 Balance in Diabetic Foot Ulcers. . 2026. PMID 41813253 · DOI · PMC12978988
- Fan Z, Li J, Zhong C, Liu D, Fan H, Jiang L, et al.. Comprehensive Review of Hydrogel-Mediated Strategies for Diabetic Wound Healing. . 2026. PMID 42123497 · DOI · PMC13163982
- Hu G, Nisar A, Khan S, Li W, Zhu E, Cui H, et al.. Comprehensive transcriptomic profiling reveals tissue-specific molecular signatures and dysregulated pathways in human diabetic foot ulcers. . 2025. PMID 41255536 · DOI · PMC12620202
- Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis †. Ann Med. 2017. PMID 27585063 · DOI
- Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis. Diabetes Care. 1999. PMID 10332667 · DOI
- Chen L, Sun S, Gao Y, Ran X. Global mortality of diabetic foot ulcer: A systematic review and meta-analysis of observational studies. Diabetes Obes Metab. 2023. PMID 36054820 · DOI
- Macdonald KE, Boeckh S, Stacey HJ, Jones JD. The microbiology of diabetic foot infections: a meta-analysis. BMC Infect Dis. 2021. PMID 34372789 · DOI · PMC8351150
- Martinez-Zapata MJ, Martí-Carvajal AJ, Solà I, Expósito JA, Bolíbar I, Rodríguez L, et al.. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev. 2016. PMID 27223580 · DOI · PMC9308064
- Lin C, Liu J, Sun H. Risk factors for lower extremity amputation in patients with diabetic foot ulcers: A meta-analysis. PLoS One. 2020. PMID 32936828 · DOI · PMC7494323
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.