Biomarkers of Healing in Chronic Diabetic Foot Ulcers

NewsBot · Sep 28, 2024

Biomarkers of local inflammation at the skin's surface may predict both pressure and diabetic foot ulcers
Pauline Wilson et al
J Wound Care. 2024 Sep 2;33(9):630-635

This commentary considers the similarities which exist between pressure ulcers (PUs) and diabetic foot ulcers (DFUs). It aims to describe what is known to be shared-both in theory and practice-by these wound types. It goes on to detail the literature surrounding the role of inflammation in both wound types. PUs occur following prolonged exposure to pressure or pressure in conjunction with shear, either due to impaired mobility or medical devices. As a result, inflammation occurs, causing cell damage. While DFUs are not associated with immobility, they are associated with altered mobility occurring as a result of complications of diabetes. The incidence and prevalence of both types of lesions are increased in the presence of multimorbidity. The prediction of either type of ulceration is challenging. Current risk assessment practices are reported to be ineffective at predicting when ulceration will occur. While systemic inflammation is easily measured, the presence of local or subclinical inflammation is harder to discern. In patients at risk of either DFUs or PUs, clinical signs and symptoms of inflammation may be masked, and systemic biomarkers of inflammation may not be elevated sufficiently to predict imminent damage until ulceration appears. The current literature suggests that the use of local biomarkers of inflammation at the skin's surface, namely oedema and temperature, may identify early tissue damage.
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NewsBot · Oct 7, 2024

Systematic review and meta-analysis of the diagnostic accuracy of inflammatory markers for infected diabetic foot ulcer
Hua Chen et al
J Tissue Viability. 2024 Sep 26

Background: The aim was to evaluate the diagnostic value of ESR, CPR, PCT, and WBC in patients with infected diabetic foot ulcer (DFU).

Methods: The MEDLINE, Embase, BIOSIS, Cochrane databases, and Web of Knowledge databases were searched, without language restriction, to July 2023. Original studies were selected that reported the performance of ESR, CPR, PCT, and WBC in diagnosing infected DFU. To assess the diagnostic value of biomarkers for infected DFU, pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (ROC-AUC) were calculated.

Results: Ten studies with 765 patients were identified in our meta-analysis. The pooled sensitivity and specificity of ESR was 0.82 (95 % CI: 0.68-0.91) and 0.83 (95 % CI: 0.69-0.91) respectively. The pooled sensitivity and specificity of CRP was 0.81 (95 % CI: 0.65-0.91) and 0.91 (95 % CI: 0.79-0.96) respectively. The pooled sensitivity and specificity of PCT was 0.76 (95 % CI: 0.65-0.85) and 0.89 (95 % CI: 0.78-0.95) respectively. The pooled sensitivity and specificity of WBC was 0.75 (95 % CI: 0.64-0.83) and 0.79 (95 % CI: 0.67-0.88) respectively. CRP showed the best diagnostic accuracy at distinguishing infected DFU from noninfected DFU with an AUC of 0.93, followed by PCT (AUC of 0.89), ESR (AUC of 0.89), and WBC (AUC of 0.84).

Conclusion: CPR levels had high efficiency in distinguishing infected DFU from noninfected DFU, followed by PCT, ESR and WBC. All of these biomarkers could be helpful for early diagnosis of infected DFU. New biomarkers for improving medical decision in diagnosis of infected DFU are highly desirable.
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NewsBot · Nov 1, 2024

Neutrophil Migration is a Crucial Factor in Wound Healing and the Pathogenesis of Diabetic Foot Ulcers: Insights into Pharmacological Interventions
Adhi Shree R et al
Curr Vasc Pharmacol. 2024 Oct 30.

Diabetic foot ulcers (DFUs) pose a significant clinical challenge, characterized by impaired wound healing, chronic inflammation, and increased risk of infection. Neutrophils, as critical components of the innate immune response, play a pivotal role in the initial stages of wound healing, particularly during the inflammatory phase. This review explores the intricate relationship between neutrophil migration, inflammation, and the pathogenesis of DFU and drugs that can impact neutrophil production and migration. Neutrophils contribute to infection control through phagocytosis and release pro-inflammatory cytokines and reactive oxygen species, which, when dysregulated, can impede the wound healing process. Furthermore, the chronic hyperglycemic state characteristic of diabetes mellitus has been implicated in impairing neutrophil functions, including chemotaxis and oxidative burst. This compromised neutrophil response prolongs the inflammatory phase and disrupts the delicate balance required for efficient wound healing. Neutrophil extracellular traps (NETs), a unique form of neutrophil defence, have also been implicated in DFU pathogenesis, potentially exacerbating inflammation and tissue damage. Understanding the intricate interplay between neutrophil migration, dysregulated inflammatory responses, and hyperglycemia-driven impairments is essential for developing targeted therapeutic strategies for DFUs. This review sheds light on the critical role of neutrophils in DFU pathogenesis, and innovative and advanced treatment strategies for DFU, highlighting the potential for novel interventions to restore the balance between pro-inflammatory and wound healing processes, ultimately improving clinical outcomes for individuals with DFU.
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NewsBot · May 28, 2025

A Metabolic Signature Specific to the Patients with Type 2 Diabetes and its Association with the Pathogenesis of Diabetic-Foot Syndrome
Tao Wang et al
J Cardiovasc Transl Res. 2025 Apr 16.

Oxidative stress and protein nonenzymatic glycation are key factors in diabetic-foot syndrome pathogenesis. Type 2 diabetes (T2DM) progression involves excessive gluconolactone (GDL) production, linked to endothelial injury and diabetic arteriosclerosis. This study explored GDL's role in diabetic-foot syndrome using high-performance liquid chromatography-tandem mass spectrometry to analyze sera from 75 T2DM patients (including 32 with diabetic-foot) and 36 healthy controls. GDL levels were significantly higher in T2DM patients and correlated with increased hemoglobin A1c glycation and reactive oxygen species production in endothelial cells, suggesting GDL's role in accelerating macrovascular arteriosclerosis and diabetic-foot syndrome. These findings highlight GDL's potential as a diagnostic biomarker and therapeutic target for diabetic macrovascular complications.
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NewsBot · May 31, 2025

Exploring The Role of Serum Netrin 1 Levels in Diabetic Foot Syndrome And Uncomplicated Type 2 Diabetes Mellitus: A Comparative Analysis
D Chaitra et al
Clin Ter. 2025 Mar-Apr;176(2):201-206.

Purpose: Serum netrin levels have been implicated in diabetes and its complications, including diabetic foot syndrome. Netrin 1, a protein encoded by the Netrin gene, has been recognized for its role in various physiological processes ranging from nervous system development to angiogenesis, inflammation, and wound healing. In the context of diabetes, there is growing interest in understanding the relationship between serum netrin levels and the disease. Studies have suggested that netrin-1 may have a role in angiogenesis and inflammatory responses, both of which are relevant to diabetes and its complications. Research has indicated that may be involved in the pathophysiology of diabetic foot syndrome, a serious complication of diabetes characterized by issues such as foot ulcers and impaired wound healing. Therefore, comparing serum netrin levels in individuals with diabetes, especially those with complications like diabetic foot syndrome, to those with uncomplicated diabetes, may provide insights into the potential association between netrin and the disease.
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NewsBot · Jun 5, 2025

Evaluation of c-Myc and Phosphorylated Glucocorticoid Receptor (p-GR) for Predicting Diabetic Foot Ulcer Healing-A Diabetic Foot Consortium Study
Robert S Kirsner et al
Wound Repair Regen. 2025 May-Jun;33(3):e70044.

Diabetic foot ulcers (DFUs) are a serious clinical problem, leading to high rates of morbidity, disability, amputations, and mortality. Many DFUs fail to heal completely and a major challenge includes identifying non-healers early in treatment. However, effective predictive biomarkers for DFUs have not yet been validated. The goal of this study was to validate if two previously identified, objective and quantitative tissue biomarkers, c-Myc and phosphorylated glucocorticoid receptor (p-GR), could predict complete healing at week 12 in a multicenter observational cohort study of individuals with open DFUs, conducted by the NIDDK Diabetic Foot Consortium (DFC). Wound tissue collected at the initial visit was analysed for c-Myc and p-GR biomarkers by immunohistochemistry, quantifying their nuclear presence in full thickness epidermis and correlating with week 12 clinical outcomes. The primary analyses included AUC comparisons to assess the biomarkers' predictive capability for wound healing. Other analyses included descriptive measures and t-tests to evaluate the difference between biomarker quantification among healers and non-healers. Of 140 DFUs enrolled, 107 participants completed biomarker and clinical outcome data for analysis. The distributions of baseline c-Myc and p-GR between healed and not-healed DFUs by week 12 were not significantly different (p > 0.05). Although the two biomarkers did not yield significant predictability (ΔAUC = -0.006, 95% CI (-0.02, 0.01) and ΔAUC = -0.0002, 95% CI (-0.01, 0.01), p > 0.025) for each of c-Myc and p-GR respectively, this first DFC clinical study using a national consortium of DFU centres successfully created a unique resource of wound-related biomaterials coupled with the clinical outcomes, providing a platform for further biomarker discovery and validation.
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NewsBot · Jun 16, 2025

Are metabolic abnormalities the missing link between complete blood count-derived inflammatory markers and diabetic foot? Evidence from a large population study
Yang Zhang ,Shumin Zhou ,Xianbin Wang,Haiyan Zhou
June 12, 2025

Background
Diabetic foot is a serious complication of diabetes, and inflammation plays a key role in its pathogenesis. This population-based study investigates associations between complete blood count (CBC)-derived inflammatory markers and diabetic foot, while evaluating metabolic mediators in these relationships.

Methods
Data from 1,246 participants across three National Health and Nutrition Examination Survey (NHANES) cycles (1999–2004) were analyzed. Calculated inflammatory markers included monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), neutrophil-monocyte-to-lymphocyte ratio (NMLR), and systemic inflammatory response index (SIRI). Weighted logistic regression models assessed marker-diabetic foot associations, supplemented by subgroup and restricted cubic spline (RCS) analyses for nonlinearity. Mediation analysis quantified metabolic contributions.

Results
CBC-derived inflammatory markers demonstrated significant positive correlations with diabetic foot risk. Risk increased as quartiles for these markers increased. RCS analysis further revealed a significant nonlinear relationship between them. Serum creatinine (12.46%) and albumin (11.33%) mediated significant proportions of these associations.

Conclusions
CBC-derived inflammatory markers serve as accessible predictors of diabetic foot risk, with nonlinear patterns. The partial mediation by metabolic indicators highlights dual inflammatory-metabolic pathways in diabetic foot pathogenesis. Routine CBC-derived inflammatory markers monitoring could enable early risk stratification, while targeting metabolic abnormalities may amplify preventive strategies.
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Biomarkers of Healing in Chronic Diabetic Foot Ulcers

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Biomarkers of Healing in Chronic Diabetic Foot Ulcers

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

Biomarkers for diabetic foot amputation prediction

Cellular Biomarkers for the Diagnosis and Treatment of Diabetic Foot Ulcer

Biomarkers for peripheral artery disease

Comprehensive Therapy vs. Standard Treatment in Diabetic Foot Ulcer Healing

Injury Afoot: 30 Things You Can Do to Relieve Heel Pain and Speed Healing of Plantar Fasciitis

Healing of diabetic neuropathic foot ulcers receiving standard treatment

Novel human keratin matrix improves healing rates

Share This Page

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