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Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: 15 October 2025 | Viewed by 10048

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Prof. Dr. Luigi Uccioli

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Diabetic Foot Unit, Department Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Interests: diabetic foot; diabetic foot ulcers; diabetic foot infections; diabetic foot osteomyelitis; diabetic symmetric polyneuropathy; peripheral atherial disease; charcot foot
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Prof. Dr. José Luis Lázaro-Martínez

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Guest Editor

Diabetic Foot Unit, Universidad Complutense de Madrid, Madrid, Spain
Interests: diabetic foot; diabetic foot ulcers; diabetic foot infections; diabetic foot osteomyelitis; diabetic symmetric polyneuropathy; charcot foot
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This is the third edition of the Special Issue “Diabetic Foot Complications: Current Challenges and Future Prospects”.

The previous two editions were quite successful, with a large number of manuscripts about different topics in diabetic foot diseases, including meta-analyses, systematic revisions, and novel studies about promising techniques that could improve diabetic foot management and lower limb ailments (https://www.mdpi.com/journal/jcm/special_issues/Diabetic_Foot_Complications_2, https://www.mdpi.com/journal/jcm/special_issues/Diabetic_Foot).

Diabetic foot is a growing complication due to the global rise in Diabetes mellitus prevalence, affecting 9.1 to 26.1 million people annually worldwide and between approximately 19% and 34% of people with diabetes at least once in their life. Diabetic foot is sometimes associated with lower limb amputations and higher rates of mortality than some kinds of cancer, such as breast cancer or prostate cancer. In recent years, evidence has been focused on the management of the main complications that lead patients to limb loss, such as diabetic foot infections or peripheral vascular disease. The majority of studies investigate outcomes over the acute phase when a patient has a complicated diabetic foot ulcer. However, long-term studies, randomized control trials, and studies on prevention, both primary and secondary, are still few in the literature. On the other hand, the benefits of a multidisciplinary team on patient outcomes, health care system organization, and the competences of different specialties and health care professionals and what the impact is of different organizational and structural approaches are not yet very well studied in the literature. With this Special Issue, we hope to encourage submissions that discuss the current state of the art, address ongoing knowledge gaps, and focus on ongoing controversies related to diabetic foot complications.

Prof. Dr. Luigi Uccioli
Prof. Dr. José Luis Lázaro-Martínez
Guest Editors

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Keywords

diabetic foot ulcers
diabetic foot infections
charcot foot
peripheral vascular disease
prevention diabetic foot
lower limb amputation
diabetic foot mortality
biomechanics of diabetic foot

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Related Special Issue

Diabetic Foot Complications: Current Challenges and Future Prospects—Part II in Journal of Clinical Medicine (16 articles)

Published Papers (10 papers)

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10 pages, 1624 KiB

Open AccessArticle

No Routine Control Measurements of C-Reactive Protein in Uneventful Postoperative Evolution After Debridement for Infected (Diabetic) Foot Surgery

by Jonas Liebe, Laura Soldevila-Boixader, İnci Yιldιz, Pascal R. Furrer, Peter Jans, Arnd Viehöfer, Stephan Wirth and İlker Uckay

J. Clin. Med. 2025, 14(12), 4122; https://doi.org/10.3390/jcm14124122 - 11 Jun 2025

Viewed by 419

Abstract

Background/Objectives: In orthopedic (diabetic) foot surgery, the serum C-reactive protein (CRP) level is frequently measured not only as a diagnostic tool, but also as a control inflammatory marker in the follow-up of postoperative surgical-site infections (SSIs) Methods: We investigated the predictive value of the post-debridement routine (control) serum CRP level in adult (diabetic) patients with an SSI in the foot. We excluded community-acquired (diabetic foot) infections and focused on the predictive accuracy of routine (control) CRP measurements in terms of ultimate therapeutic failures. Results: The median pre- and postoperative CRP levels were 25 mg/L and 8.8 mg/L, respectively. In group comparisons and multivariate assessment, neither the immediate (relative and absolute) drop in the serum CRP level, nor its values between 5 and 8 weeks and between 11 and 14 weeks predicted the failure risk of 19%. In contrast, in cases of surprisingly elevated CRP levels, this finding leads to unnecessary radiological (median costs approximatively USD 200), clinical, microbiological urinary sample (median costs USD 50), and laboratory (one CRP sample USD 10) exams. These additional exams also likely prolong the duration of hospitalization by one to two days (e.g., whilst awaiting the microbiological results) and often generate unnecessary consultations among internist and/or infectious diseases experts (USD 50). Conclusions: Routine, postoperative CRP monitoring during the treatment of established orthopedic (diabetic) foot SSIs is unnecessarily costly, and should be avoided in favor of clinical surveillance of the postoperative evolution. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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19 pages, 1563 KiB

Open AccessArticle

Short-Term Efficacy of a Multi-Modal Intervention Program to Improve Custom-Made Footwear Use in People at High Risk of Diabetes-Related Foot Ulceration

by Jaap J. Van Netten, Lisa E. Vossen, Faye M. Driebergen, Danne Wolthuis, Maarten J. M. Merkx and Sicco A. Bus

J. Clin. Med. 2025, 14(11), 3635; https://doi.org/10.3390/jcm14113635 - 22 May 2025

Viewed by 592

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Background: Wearing custom-made footwear is key in diabetes-related foot ulcer prevention. However, adhering to wearing footwear is challenging, in particular at home. Evidence-based interventions with proven effect are needed, but scarce. We developed a multi-modal intervention to improve custom-made footwear use, and investigated short-term efficacy. Methods: We used a multidisciplinary multiphase approach to develop a three-modality intervention: structured education, motivational interviewing, and custom-made indoor footwear. To assess efficacy, we measured mean 2-week wearing time of custom-made footwear with a validated sensor, at baseline and after three months (primary outcome), and in the two weeks directly before and after each modality was administered (secondary outcomes). We assessed differences between timepoints using within-subjects paired t-tests. Results: 53 participants with high risk for ulceration were included: 30 with low [<8 h/day] baseline adherence), 17% females, mean age 66 (SD: 10) years, all with peripheral neuropathy and a recent foot ulcer (mean time since healing: 6 (SD: 9) months). Wearing time increased non-significantly from 4.0 (SD: 2.5) at baseline to 5.5 (SD: 4.3) after three months in the low adherence group (p = 0.068); this was 11.9 (SD: 2.3) to 12.0 (SD: 2.8) in the high adherence group (p = 0.898). Following provision of indoor footwear, wearing time increased significantly for low baseline adherence (∆2.7 h/day (95% CI: 1.0–4.4; p = 0.004) and high baseline adherence (∆2.0 h/day (95% CI: 0.5–3.4; p = 0.010). Following structured education, wearing time increased non-significantly in those with low baseline adherence (∆1.0 h/day (95% CI: −0.2–2.2; p = 0.098). Following motivational interviewing, wearing time remained similar in both groups. Conclusions: The multi-modal intervention program combining structured education, motivational interviewing and custom-made indoor footwear did not result in a statistically significant improvement in the wearing time of custom-made footwear after three months. However, significant improvements followed the provision of indoor footwear, and clinically relevant improvements followed structured education in people with low adherence, providing avenues for implementation and research. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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17 pages, 557 KiB

Open AccessArticle

Social Support and Disease Acceptance in Patients with Diabetic Foot Syndrome and Their Relationship with the Metabolic Control of the Disease

by Ewa Kobos, Olga Serafin, Ewa Kostrzewa-Zabłocka and Anna Stefanowicz-Bielska

J. Clin. Med. 2025, 14(10), 3412; https://doi.org/10.3390/jcm14103412 - 13 May 2025

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Background: Diabetic foot syndrome (DFS) constitutes a serious clinical challenge in the treatment of diabetes. The aim of this study was to assess social support and acceptance of the disease in patients with diabetic foot syndrome and their relationship with the metabolic control of diabetes. Methods: This was an observational, single-center study, conducted in 80 people hospitalized in the general and vascular surgery department. This study included adult patients with type 1 or type 2 diabetes, diagnosed with DFS. The mean age of the patients was 65.63 years, with the median age of 62 years. The youngest patient was 27, and the oldest was 94 years old. Men constituted 71.25% of the study group, women 28.75%. The following data were collected: the results of laboratory tests and measurements, the Acceptance of Illness Scale (AIS), and the Social Support Scale (S4-MAD) scores. Results: Abnormal values of non-high-density lipoprotein cholesterol (mean (M) = 120.76 mg/dL) and low-density lipoprotein cholesterol (M = 144.56) were shown in all the patients. Abnormal low-density lipoprotein values occurred in 98.75% of the patients (M = 148.21 mg/dL), and 83.75% of the participants had abnormal values of the systolic pressure (M = 145 mmHg) and total cholesterol. Glycated hemoglobin was abnormal in 61.25% of the subjects (M = 8.95%). The average score on the Acceptance of Illness Scale was 18.4 points in the study group. Out of the 100 possible points in the subscales of social support, the patients obtained an average of 46.5 points in the nutrition dimension, 40 for physical activity, 47.1 for glycemic self-control, 27.4 for foot care, and 68.9 for smoking. Conclusions: Patients with diabetic foot syndrome are characterized by poor acceptance of the disease and receive moderate social support. Patients receive the highest support in terms of cigarette smoking and glycemic self-control, with the lowest in foot care. The patient’s acceptance of the disease and the social support received are unrelated to the patient’s goals of disease control. Higher social support received by the DFS patients is associated with a greater acceptance of the disease. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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16 pages, 5835 KiB

Open AccessArticle

Chronic Ulcers Healing Prediction through Machine Learning Approaches: Preliminary Results on Diabetic Foot Ulcers Case Study

by Elisabetta Spinazzola, Guillaume Picaud, Sara Becchi, Monica Pittarello, Elia Ricci, Marc Chaumont, Gérard Subsol, Fabio Pareschi, Luc Teot and Jacopo Secco

J. Clin. Med. 2025, 14(9), 2943; https://doi.org/10.3390/jcm14092943 - 24 Apr 2025

Viewed by 884

Abstract

Background: Chronic diabetic foot ulcers are a global health challenge, affecting approximately 18.6 million individuals each year. The timely and accurate prediction of wound healing paths is crucial for improving treatment outcomes and reducing complications. Methods: In this study, we apply predictive modeling to the case study of diabetic foot ulcers, analyzing and comparing multiple models based on Deep Neural Networks (DNNs) and Machine Learning (ML) algorithms to enhance wound prognosis and clinical decision making. Our approach leverages a dataset of 1766 diabetic foot wounds, each monitored for at least three visits, incorporating key clinical wound features such as WBP scores, wound area, depth, and tissue status. Results: Among the 12 models evaluated, the highest accuracy (80%) was achieved using a three-layer LSTM recurrent DNN trained on wound instances with four visits. The model performance was assessed through AUC (0.85), recall (0.80), precision (0.79), and F1-score (0.80). Our findings indicate that the wound depth and area at the first visit followed by the wound area and granulated tissue percentage at the second visit are the most influential factors in predicting the wound status. Conclusions: As future developments, we started building a weakly supervised semantic segmentation model that classifies wound tissues into necrosis, slough, and granulation, using tissue color proportions to further improve model performance. This research underscores the potential of predictive modeling in chronic wound management, specifically in the case of diabetic foot ulcers, offering a tool that can be seamlessly integrated into routine clinical practice. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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10 pages, 639 KiB

Open AccessArticle

The Performance of Gram-Staining in Tailoring the Empirical Antibiotic Choice in Operated Diabetic Foot Infections

by Dominique Altmann, Jonas Liebe, Felix W. A. Waibel, Madlaina Schöni, Francesca Napoli, Christina Sydler, Fabian Schläfli, Linus Ledermann, Benjamin A. Lipsky and Ilker Uçkay

J. Clin. Med. 2025, 14(7), 2468; https://doi.org/10.3390/jcm14072468 - 4 Apr 2025

Viewed by 1409

Abstract

Background/Objectives: Current international guidelines recommend choosing an empirical antibiotic regimen for treating diabetic foot infections (DFI) based largely on clinical severity of the infection and local microbiological epidemiology. This may lead to selecting unnecessarily broad-spectrum initial empiric antibiotic therapy. Methods: Using data from our hospital in a large Swiss city, we retrospectively analyzed the performance of the Gram-stained smears of predominantly deep surgical DFI specimens processed by our microbiology laboratory in predicting the microorganism grown on standard cultures. We excluded episodes with paucibacillary stain results, which we interpret as contamination. Results: Among 1235 operated moderates or severe DFIs, Gram-stained smear was reported in 321 (26%) of cases, and showed bacteria in 172 episodes (54%) of these. Overall, among Gram stain results with organism seen, the sensitivity, specificity, accuracy, positive and negative predictive values of the Gram stain smear when compared with the cultures was 56%, 93%, 97%, and 38%, respectively. The accuracy was 73%. The corresponding statistical values specifically for Gram-negative bacteria were 61%, 97%, 50%, and 82%. Conclusions: The results of routine Gram stain smears of deep intraoperative DFI specimens generally lack sufficient sensitivity, and was only useful to reasonably exclude a DFI caused predominantly by Gram-negative bacteria. For Gram-stained smears results to be useful for guiding antibiotic stewardship, we need prospective trials to assess their value in different types of DFIs. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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15 pages, 559 KiB

Open AccessArticle

The Burden of Diabetic Foot Ulcers on Hospital Admissions and Costs in Romania

by Adriana Rusu, Gabriela Roman, Bogdan Stancu and Cornelia Bala

J. Clin. Med. 2025, 14(4), 1248; https://doi.org/10.3390/jcm14041248 - 13 Feb 2025

Viewed by 919

Abstract

Background/Objectives: Diabetic foot ulcers represent an important economic burden for healthcare systems worldwide. We aimed to analyze the costs of care for diabetic foot ulcers (DFUs) associated with peripheral neuropathy (DPN) and peripheral arterial disease (PAD) and their trends in a tertiary-care hospital. Methods: We used data from the electronic system of the Emergency Clinical County Hospital Cluj-Napoca, Romania. We included all episodes of hospitalization with a discharge date between 1 January 2015 and the 31 December 2018 and a discharge diagnosis of type 1 or type 2 diabetes, DPN, PAD, and foot ulcers. Results: During the analyzed period, 1094 episodes of hospitalization with type 1 or type 2 diabetes and DFUs were recorded. Of these, 25.9% had neuropathic, 47.1% ischemic, and 16.6% neuroischemic DFUs. The median length of hospital stay was 8.0 days, and the median cost per episode of hospitalization was 810.8 EUR, with no significant variations during the analyzed years. The cost per episode of hospitalization was higher in cases with ischemic DFUs than for other etiologies of foot ulcers for 2015–2017 (p < 0.001). In 2018, the costs for ischemic and neuroischemic DFUs were similar and significantly higher compared to neuropathic ones. Predictors of higher costs per episode of hospitalization included the etiology of the DFUs (β = 0.032, p = 0.034) and the length of hospital stay (β = 0.860, p < 0.001). Conclusions: By analyzing data from a tertiary care hospital, we showed higher costs for the care of persons with ischemic DFU. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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12 pages, 1201 KiB

Open AccessArticle

The Appropriateness of Footwear in Diabetic Patients Observed during a Podiatric Examination: A Prospective Observational Study

by Anisa Hazbiu, Ilaria Teobaldi, Mario Sepe, Giovanni Federici, Marco Meloni and Luigi Uccioli

J. Clin. Med. 2024, 13(8), 2402; https://doi.org/10.3390/jcm13082402 - 20 Apr 2024

Viewed by 2160

Abstract

Background: Adequate compliance with wearing therapeutic footwear (TF) to prevent diabetic foot ulcers is known to be low. The primary aim of this study was to identify population awareness about the ulceration and/or recurrence risk according to footwear choice. The secondary aim was to evaluate the compliance level in footwear choice based on a patient’s own risk. Methods: Forty podiatrists participated from 1 September 2017 to 31 August 2018, providing six-section forms which included personal data, risk classification, footwear characteristics and a knowledge questionnaire. Results: This study included 1507 patients. Those with active ulcers were excluded. A total of 43% of patients belonged to risk class 0, 19% to risk class 1, 19% to risk class 2 and 19% to risk class 3. A total of 58% had foot deformities. Conclusions: Nearly half of patients with a high risk of ulceration had knowledge of their own risk but the majority of them did not follow the recommendations. Only a small percentage (36%) of risk class 3 patients wore footwear suitable for their risk class. There was poor consideration of footwear choice among patients. We highlight critical issues in patient education and compliance with wearing footwear appropriate to their risk class. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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9 pages, 431 KiB

Open AccessArticle

Diagnostic Performance of Atherogenic Index of Plasma for Predicting Diabetic Foot Osteomyelitis with Peripheral Artery Disease

by Sebastián Flores-Escobar, Mateo López-Moral, Marta García-Madrid, Francisco J. Álvaro-Afonso, Aroa Tardáguila-García and José Luis Lázaro-Martínez

J. Clin. Med. 2024, 13(7), 1934; https://doi.org/10.3390/jcm13071934 - 27 Mar 2024

Cited by 4 | Viewed by 1464

Abstract

Background: This study aims to assess the atherogenic index of plasma (AIP) diagnostic value in detecting diabetic foot osteomyelitis (DFO) among patients with diabetic foot ulcers (DFUs). Methods: A prospective cohort study was conducted on 80 patients with DFUs and suspected DFO between January 2022 and December 2023. The primary outcome measures included the diagnosis of DFO, determined by positive microbiological analysis results from bone samples and its correlation with the AIP. Receiver operating characteristic (ROC) curves were utilized to select the optimal diagnostic cut-off points for AIP and post hoc analysis was performed to evaluate the difference in the AIP for diagnosing DFO in patients with and without peripheral arterial disease (PAD). Results: The diagnostic potential for DFO in PAD patients of AIP-1 (Log TC/HDL) showed an AUC of 0.914 (p < 0.001 [0.832–0.996]), leading to a sensitivity of 83% and a specificity of 85%. By contrast, AIP-2 (Log TG/HDL) demonstrated a slightly lower AUC of 0.841 (p < 0.001 [0.716–0.967]), leading to a sensitivity of 76% and a specificity of 74%. Conclusions: The AIP tool, with its ideal blend of sensitivity and specificity, aids in predicting DFO effectively. Therefore, clinicians should consider using AIP for patients suffering from PAD and associated DFO. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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Review

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11 pages, 1048 KiB

Open AccessReview

Minimally Invasive Drainage for Diabetic Foot Phlegmon

by Marco Cavallini

J. Clin. Med. 2025, 14(11), 3918; https://doi.org/10.3390/jcm14113918 - 3 Jun 2025

Viewed by 635

Abstract

Treatment for deep diabetic foot ulcers (DFUs) and infections (DFIs) includes debridement of any dead/infected non-viable tissue, systemic antibiotics, and surgical drainage to avoid exudate stasis. Surgical drainage can cause extended incisions leading to long scars which expose these sites to ulcer recurrence and inadequate rehabilitation. In order to treat the negative impact of stasis on wound healing, we have designed an easy, minimally invasive surgical drainage technique which allows adequate ulcer cleansing by daily irrigation of any drained tract. A probe is passed along the ulcer’s infected recesses until the end and pushed against the skin, which is incised and pierced. A small 6 Fr-size silastic tube is then anchored to the probe and pulled backwards. The two ends of the tube are tied together to construct an ulcer-piercing drainage (UPD) ring. The UPD ring is designed to keep any tract open for irrigation with a syringe through both sides of the skin opening. The UPD procedure is easy and safe. The constructed blocked ring of tubing the system avoids the possibility for drainage displacement or accidental removal and can be easily utilized by any home caregiver. The UPD and irrigation are useful to provide any recess cleansing, reduce critical and negative ulcer bioburden and bacterial load, and it could avoid unnecessary and untimely extended surgical incisions leading to long uncomfortable scars, inadequate rehabilitation, relapses, or distal amputations. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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7 pages, 195 KiB

Open AccessBrief Report

The Post-Healing Follow-Up of Diabetic Foot Ulcers by a Multidisciplinary Team to Reduce Their Recurrence: An Observational Retrospective Study

by Marie Bouly, Francois-Xavier Laborne, Caroline Tourte, Elodie Henry, Alfred Penfornis and Dured Dardari

J. Clin. Med. 2025, 14(14), 4975; https://doi.org/10.3390/jcm14144975 - 14 Jul 2025

Viewed by 174

Abstract

Background: Diabetic foot disease is a public health problem. The challenges of its management lie in the complexity of wound healing and, in particular, the high rate of lesion recurrence. Objectives: The primary objective of the study was to evaluate whether optimized post-healing follow-up by a multidisciplinary team can reduce the recurrence rate of foot ulcers in people living with diabetes. The secondary objectives were to assess patient needs in terms of hospitalization for recurrence, the number of amputations, pedicure care, and the use of adapted footwear. Participants: The study included 129 patients with diabetes presenting a healed foot ulcer. A total of 38 patients underwent an annual post-healing follow-up visit with a multidisciplinary team (optimized follow-up), while 91 had a visit every 2 years (minimum follow-up). Results: Of the 38 patients with optimal follow-up, 8 presented a wound recurrence (21.1%) compared with 38 out of 91 patients (41.8%) receiving minimum follow-up. The recurrence rate decreased significantly between the two groups (p < 0.05). The use of adapted shoes was also significantly better in the group with optimized follow-up (p = 0.02). Conclusions: Regular post-healing follow-up with a multidisciplinary team seems to be a contributing factor to reducing the recurrence of diabetic foot ulcers among people living with diabetes. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects—3rd Edition)

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