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The Diabetic Foot: Recent Advances and Future Developments

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A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Endocrinology".

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 97414

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Dr. Loretta Vileikyte

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Guest Editor

1. Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
2. Diabetes Research Institute, University of Miami, Miami, FL, USA
Interests: diabetic foot ulceration; neuropathic diabetic foot; diabetes care

Special Issue Information

Dear Colleagues,

Of all the diabetes complications that occur, foot ulceration is among the most debilitating and costly, with morbidity and mortality rates being worse than for many cancers. Nonetheless, research into diabetic foot ulcer prevention and management is making great strides.

Therefore, the editorial decision of Medicina to dedicate this Special Issue to the topic of diabetic foot complications could not be better timed or more fitting.

In this issue, we will discuss how innovative approaches and smart technologies may optimize the management and prevention of foot ulceration by identifying high-risk patients for timely interventions, personalizing foot ulcer offloading, and improving adherence to protective footwear. The advent of the COVID-19 pandemic has resulted in a paradigm shift in the delivery of care for those with diabetic foot ulcers. This has produced many challenges but also opportunities for the delivery of foot care. Thanks to advances in smartphones, mobile applications, smart wearables, and telemedicine, the “hospital- at-home” care delivery model has started to replace the traditional “face-to-face” clinical care approach.

In addition to advances in established treatment modalities, such as the management of infections and osteomyelitis, there has been a renaissance of local treatments including topical oxygen therapies. Furthermore, psychological stress and, in particular, depression have gained recognition as important determinants of foot ulcer development and impaired healing, while growing insights into the biomechanics of the diabetic foot have resulted in more effective foot ulcer prevention and treatment.

These are some of the many scientific developments in the field of the diabetic foot. We therefore encourage original publications that would further advance our medical knowledge of this all too common and devastating complication of diabetes.

Dr. Loretta Vileikyte
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

diabetic foot ulceration
smart technologies
telemedicine
infection
topical treatments
psychological stress
biomechanics
ulcer offloading

Published Papers (10 papers)

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Research

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14 pages, 940 KiB

Open AccessArticle

Site-Specific, Critical Threshold Barefoot Peak Plantar Pressure Associated with Diabetic Foot Ulcer History: A Novel Approach to Determine DFU Risk in the Clinical Setting

by Caroline A. Abbott, Katie E. Chatwin, Satyan M. Rajbhandari, Kanwal M. John, Sushma Pabbineedi, Frank L. Bowling, Andrew J. M. Boulton and Neil D. Reeves

Medicina 2022, 58(2), 166; https://doi.org/10.3390/medicina58020166 - 21 Jan 2022

Cited by 6 | Viewed by 3848

Abstract

Background and Objectives: Barefoot peak plantar pressures (PPPs) are elevated in diabetes patients with neuropathic foot ulcer (DFU) history; however, there is limited reported evidence for a causative link between high barefoot PPP and DFU risk. We aimed to determine, using a simple mat-based methodology, the site-specific, barefoot PPP critical threshold that will identify a plantar site with a previous DFU. Materials and Methods: In a cross-sectional study, barefoot, site-specific PPPs were measured with normal gait for patients with DFU history (n = 21) and healthy controls (n = 12), using a validated carbon footprint system. For each participant, PPP was recorded at twelve distinct plantar sites (1st–5th toes, 1st–5th metatarsal heads (MTHs), midfoot and heel), per right and left foot, resulting in the analysis of n = 504 distinct plantar sites in the diabetes group, and n = 288 sites in the control group. Receiver operator characteristic curve analysis determined the optimal critical threshold for sites with DFU history. Results: Median PPPs for the groups were: diabetes sites with DFU history (n = 32) = 5.0 (3.25–7.5) kg/cm², diabetes sites without DFU history (n = 472) = 3.25 (2.0–5.0) kg/cm², control sites (n = 288) = 2.0 (2.0–3.25) kg/cm²; (p < 0.0001). Diabetes sites with elevated PPP (>6 kg/cm²) were six times more likely to have had DFU than diabetes sites with PPP ≤ 6 kg/cm² (OR = 6.4 (2.8–14.6, 95% CI), p < 0.0001). PPP > 4.1 kg/cm² was determined as the optimal critical threshold for identifying DFU at a specific plantar site, with sensitivity/specificity = 100%/79% at midfoot; 80%/65% at 5th metatarsal head; 73%/62% at combined midfoot/metatarsal head areas. Conclusions: We have demonstrated, for the first time, a strong, site-specific relationship between elevated barefoot PPP and previous DFU. We have determined a critical, highly-sensitive, barefoot PPP threshold value of >4.1 kg/cm², which may be easily used to identify sites of previous DFU occurrence and, therefore, increased risk of re-ulceration. This site-specific approach may have implications for how high PPPs should be investigated in future trials. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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11 pages, 1181 KiB

Open AccessArticle

The Effect of Structured Exercise Compared with Education on Neuropathic Signs and Symptoms in People at Risk of Neuropathic Diabetic Foot Ulcers: A Randomized Clinical Trial

by Byron M. Perrin, Jessica Southon, Jane McCaig, Isabelle Skinner, Timothy C. Skinner and Michael I. C. Kingsley

Medicina 2022, 58(1), 59; https://doi.org/10.3390/medicina58010059 - 30 Dec 2021

Cited by 8 | Viewed by 3521

Abstract

Background and Objectives: Lifestyle interventions such as exercise prescription and education may play a role in the management of peripheral neuropathy in people with diabetes. The aim of this study was to determine the effect of undertaking an exercise program in comparison with an education program on the signs and symptoms of peripheral neuropathy in people with diabetes at risk of neuropathic foot ulceration. Materials and Methods: Twenty-four adult participants with diabetes and peripheral neuropathy were enrolled in this parallel-group, assessor blinded, randomised clinical trial. Participants were randomly allocated to one of two 8-week lifestyle interventions, exercise or education. The primary outcome measures were the two-part Michigan Neuropathy Screening Instrument (MNSI) and vibratory perception threshold (VPT). Secondary outcome measures included aerobic fitness, balance and lower limb muscular endurance. Results: Participants in both lifestyle interventions significantly improved over time for MNSI clinical signs (MD: −1.04, 95% CI: −1.68 to −0.40), MNSI symptoms (MD: −1.11, 95% CI: −1.89 to −0.33) and VPT (MD: −4.22, 95% CI: −8.04 to −0.40). Although the interaction effects did not reach significance, changes in values from pre to post intervention favoured exercise in comparison to control for MNSI clinical signs (MD −0.42, 95% CI −1.72 to 0.90), MNSI clinical symptoms (MD −0.38, 95% CI −1.96 to 1.2) and VPT (MD −4.22, 95% CI −12.09 to 3.65). Conclusions: Eight weeks of exercise training or lifestyle education can improve neuropathic signs and symptoms in people with diabetes and peripheral neuropathy. These findings support a role for lifestyle interventions in the management of peripheral neuropathy. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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Review

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10 pages, 609 KiB

Open AccessReview

Patient and Provider Perspective of Smart Wearable Technology in Diabetic Foot Ulcer Prevention: A Systematic Review

by Giorgio Orlando, Yeliz Prior, Neil D. Reeves and Loretta Vileikyte

Medicina 2021, 57(12), 1359; https://doi.org/10.3390/medicina57121359 - 13 Dec 2021

Cited by 7 | Viewed by 4607

Abstract

Background and Objectives: Smart wearable devices are effective in diabetic foot ulcer (DFU) prevention. However, factors determining their acceptance are poorly understood. This systematic review aims to examine the literature on patient and provider perspectives of smart wearable devices in DFU prevention. Materials and Methods: PubMed, Scopus, and Web of Science were systematically searched up to October 2021. The selected articles were assessed for methodological quality using the quality assessment tool for studies with diverse designs. Results: A total of five articles were identified and described. The methodological quality of the studies ranged from low to moderate. Two studies employed a quantitative study design and focused on the patient perspective, whereas three studies included a mixed, quantitative/qualitative design and explored patient or provider (podiatrist) perspectives. Four studies focused on an insole system and one included a smart sock device. The quantitative studies demonstrated that devices were comfortable, well designed and useful in preventing DFU. One mixed design study reported that patients did not intend to adopt an insole device in its current design because of malfunctions, a lack of comfort. and alert intrusiveness, despite the general perception that the device was a useful tool for foot risk monitoring. Two mixed design studies found that performance expectancy was a predictor of a podiatrist’s behavioural intention to recommend an insole device in clinical practice. Disappointing participant experiences negatively impacted the podiatrists’ intention to adopt a smart device. The need for additional refinements of the device was indicated by patients and providers before its use in this population. Conclusions: The current evidence about patient and provider perspectives on smart wearable technology is limited by scarce methodological quality and conflicting results. It is, thus, not possible to draw definitive conclusions regarding acceptability of these devices for the prevention of DFU in people with diabetes. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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24 pages, 1219 KiB

Open AccessEditor’s ChoiceReview

Diabetic Wound-Healing Science

by Jamie L. Burgess, W. Austin Wyant, Beatriz Abdo Abujamra, Robert S. Kirsner and Ivan Jozic

Medicina 2021, 57(10), 1072; https://doi.org/10.3390/medicina57101072 - 08 Oct 2021

Cited by 164 | Viewed by 31647

Abstract

Diabetes mellitus is an increasingly prevalent chronic metabolic disease characterized by prolonged hyperglycemia that leads to long-term health consequences. It is estimated that impaired healing of diabetic wounds affects approximately 25% of all patients with diabetes mellitus, often resulting in lower limb amputation, with subsequent high economic and psychosocial costs. The hyperglycemic environment promotes the formation of biofilms and makes diabetic wounds difficult to treat. In this review, we present updates regarding recent advances in our understanding of the pathophysiology of diabetic wounds focusing on impaired angiogenesis, neuropathy, sub-optimal chronic inflammatory response, barrier disruption, and subsequent polymicrobial infection, followed by current and future treatment strategies designed to tackle the various pathologies associated with diabetic wounds. Given the alarming increase in the prevalence of diabetes, and subsequently diabetic wounds, it is imperative that future treatment strategies target multiple causes of impaired healing in diabetic wounds. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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18 pages, 828 KiB

Open AccessReview

Knee-High Devices Are Gold in Closing the Foot Ulcer Gap: A Review of Offloading Treatments to Heal Diabetic Foot Ulcers

by Peter A. Lazzarini and Gustav Jarl

Medicina 2021, 57(9), 941; https://doi.org/10.3390/medicina57090941 - 06 Sep 2021

Cited by 12 | Viewed by 4000

Abstract

Diabetic foot ulcers (DFU) are a leading cause of the global disease burden. Most DFUs are caused, and prolonged, by high plantar tissue stress under the insensate foot of a person with peripheral neuropathy. Multiple different offloading treatments have been used to try to reduce high plantar tissue stress and heal DFUs, including bedrest, casting, offloading devices, footwear, and surgical procedures. The best offloading treatments are those that balance the benefits of maximizing reductions in high plantar tissue stress, whilst reducing the risks of poor satisfaction, high costs and potential adverse events outcomes. This review aimed to summarize the best available evidence on the effects of offloading treatments to heal people with DFUs, plus review their use in clinical practice, the common barriers and solutions to using these treatments, and discuss promising emerging solutions that may improve offloading treatments in future. Findings demonstrate that knee-high offloading devices, non-removable or removable knee-high devices worn for all weight-bearing activities, are the gold standard offloading treatments to heal most patients with DFU, as they are much more effective, and typically safer, quicker, and cheaper to use compared with other offloading treatments. The effectiveness of offloading treatments also seems to increase when increased offloading mechanical features are incorporated within treatments, including customized insoles, rocker-bottom soles, controlled ankle motion, and higher cast walls. However, in clinical practice these gold standard knee-high offloading devices have low rates of prescription by clinicians and low rates of acceptance or adherence by patients. The common barriers resulting in this low use seem to surround historical misperceptions that are mostly dispelled by contemporary evidence. Further, research is now urgently required to close the implementation gap between the high-quality of supporting evidence and the low use of knee-high devices in clinical practice to reduce the high global disease burden of DFU in future. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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9 pages, 568 KiB

Open AccessReview

Topical Wound Oxygen Therapy in the Treatment of Chronic Diabetic Foot Ulcers

by Robert G. Frykberg

Medicina 2021, 57(9), 917; https://doi.org/10.3390/medicina57090917 - 31 Aug 2021

Cited by 31 | Viewed by 10380

Abstract

Oxygen is a critical component of many biological processes and is essential for wound healing. Chronic wounds are typically characterized as being hypoxic in that the partial pressure of oxygen (pO₂) in the center of the wound is often below a critical threshold necessary to fully support those enzymatic processes necessary for tissue repair. Providing supplemental oxygen can effectively raise pO₂ levels to better optimize functioning of these essential enzymes. While hyperbaric oxygen therapy has been well studied in this regard, comparative clinical studies have fallen short of providing clear evidence in support of this modality for healing chronic diabetic foot ulcers (DFU). Topical oxygen therapy (TOT) has been in clinical use for over 50 years with encouraging pre-clinical and clinical studies that have shown improved healing rates when compared to standard care. Nonetheless, TOT has heretofore been discounted as an unproven wound healing modality without theoretical or clinical evidence to support its use. This review shall provide a brief summary of the role of oxygen in wound healing and, specifically, discuss the different types of topical oxygen devices and associated studies that have convincingly shown their efficacy in healing chronic DFUs. The time has come for topical oxygen therapy to be embraced as a proven adjunctive modality in this regard. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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14 pages, 1049 KiB

Open AccessEditor’s ChoiceReview

Sensory-Motor Mechanisms Increasing Falls Risk in Diabetic Peripheral Neuropathy

by Neil D. Reeves, Giorgio Orlando and Steven J. Brown

Medicina 2021, 57(5), 457; https://doi.org/10.3390/medicina57050457 - 08 May 2021

Cited by 27 | Viewed by 11356

Abstract

Diabetic peripheral neuropathy (DPN) is associated with peripheral sensory and motor nerve damage that affects up to half of diabetes patients and is an independent risk factor for falls. Clinical implications of DPN-related falls include injury, psychological distress and physical activity curtailment. This review describes how the sensory and motor deficits associated with DPN underpin biomechanical alterations to the pattern of walking (gait), which contribute to balance impairments underpinning falls. Changes to gait with diabetes occur even before the onset of measurable DPN, but changes become much more marked with DPN. Gait impairments with diabetes and DPN include alterations to walking speed, step length, step width and joint ranges of motion. These alterations also impact the rotational forces around joints known as joint moments, which are reduced as part of a natural strategy to lower the muscular demands of gait to compensate for lower strength capacities due to diabetes and DPN. Muscle weakness and atrophy are most striking in patients with DPN, but also present in non-neuropathic diabetes patients, affecting not only distal muscles of the foot and ankle, but also proximal thigh muscles. Insensate feet with DPN cause a delayed neuromuscular response immediately following foot–ground contact during gait and this is a major factor contributing to increased falls risk. Pronounced balance impairments measured in the gait laboratory are only seen in DPN patients and not non-neuropathic diabetes patients. Self-perception of unsteadiness matches gait laboratory measures and can distinguish between patients with and without DPN. Diabetic foot ulcers and their associated risk factors including insensate feet with DPN and offloading devices further increase falls risk. Falls prevention strategies based on sensory and motor mechanisms should target those most at risk of falls with DPN, with further research needed to optimise interventions. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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22 pages, 2671 KiB

Open AccessReview

Harnessing Digital Health Technologies to Remotely Manage Diabetic Foot Syndrome: A Narrative Review

by Bijan Najafi and Ramkinker Mishra

Medicina 2021, 57(4), 377; https://doi.org/10.3390/medicina57040377 - 14 Apr 2021

Cited by 31 | Viewed by 7492

Abstract

About 422 million people worldwide have diabetes and approximately one-third of them have a major risk factor for diabetic foot ulcers, including poor sensation in their feet from peripheral neuropathy and/or poor perfusion to their feet from peripheral artery disease. The current healthcare ecosystem, which is centered on the treatment of established foot disease, often fails to adequately control key reversible risk factors to prevent diabetic foot ulcers leading to unacceptable high foot disease amputation rate, 40% recurrence of ulcers rate in the first year, and high hospital admissions. Thus, the latest diabetic foot ulcer guidelines emphasize that a paradigm shift in research priority from siloed hospital treatments to innovative integrated community prevention is now critical to address the high diabetic foot ulcer burden. The widespread uptake and acceptance of wearable and digital health technologies provide a means to timely monitor major risk factors associated with diabetic foot ulcer, empower patients in self-care, and effectively deliver the remote monitoring and multi-disciplinary prevention needed for those at-risk people and address the health care access disadvantage that people living in remote areas. This narrative review paper summarizes some of the latest innovations in three specific areas, including technologies supporting triaging high-risk patients, technologies supporting care in place, and technologies empowering self-care. While many of these technologies are still in infancy, we anticipate that in response to the Coronavirus Disease 2019 pandemic and current unmet needs to decentralize care for people with foot disease, we will see a new wave of innovations in the area of digital health, smart wearables, telehealth technologies, and “hospital-at-home” care delivery model. These technologies will be quickly adopted at scale to improve remote management of diabetic foot ulcers, smartly triaging those who need to be seen in outpatient or inpatient clinics, and supporting acute or subacute care at home. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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17 pages, 5199 KiB

Open AccessReview

Treating Diabetic Foot Osteomyelitis: A Practical State-of-the-Art Update

by Benjamin A. Lipsky and İlker Uçkay

Medicina 2021, 57(4), 339; https://doi.org/10.3390/medicina57040339 - 01 Apr 2021

Cited by 19 | Viewed by 11450

Abstract

Background and Objectives: Diabetic foot osteomyelitis (DFO) can be difficult to treat and securing optimal clinical outcomes requires a multidisciplinary approach involving a wide variety of medical, surgical and other health care professionals, as well as the patient. Results of studies conducted in the past few years have allowed experts to formulate guidelines that can improve clinical outcomes. Material and Methods: We conducted a narrative review of the literature on treat- ment of DFO, with an emphasis on studies published in the last two years, especially regarding antimicrobial therapies and surgical approached to treatment of DFO, supplemented by our own extensive clinical and research experience in this field. Results: Major amputations were once com- mon for DFO but, with improved diagnostic and surgical techniques, “conservative” surgery (foot- sparing, resecting only the infected and necrotic bone) is becoming commonplace, especially for forefoot infections. Traditional antibiotic therapy, which has been administered predominantly in- travenously and frequently for several months, can often be replaced by appropriately selected oral antibiotic regimens following only a brief (or even no) parenteral therapy, and given for no more than 6 weeks. Based on ongoing studies, the recommended duration of treatment may soon be even shorter, especially for cases in which a substantial portion of the infected bone has been resected. Using the results of cultures (preferably of bone specimens) and antimicrobial stewardship princi- ples allows clinicians to select evidence-based antibiotic regimens, often of a limited pathogen spec- trum. Intra-osseous antimicrobial and surgical approaches to treatment are also evolving in light of ongoing research. Conclusions: In this narrative, evidenced-based review, taking consideration of principles of antimicrobial stewardship and good surgical practice, we have highlighted the recent literature and offered practical, state-of-the-art advice on the antibiotic and surgical management of DFO. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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9 pages, 1088 KiB

Open AccessEditor’s ChoiceReview

Diabetic Foot Disease during the COVID-19 Pandemic

by Andrew J. M. Boulton

Medicina 2021, 57(2), 97; https://doi.org/10.3390/medicina57020097 - 22 Jan 2021

Cited by 20 | Viewed by 5721

Abstract

Throughout 2020, the COVID-19 pandemic has had a major impact on the care of non-communicable diseases across the world and diabetes is no exception. Whereas many branches of medicine have adapted to telemedicine, this is difficult and challenging for the diabetic foot which often requires “hands on” treatment. This review covers the challenges that have faced clinicians across the world in the management of complex diabetic foot problems and also includes some illustrative case vignettes which show how it is possible to manage foot ulcers without the usual access to laboratory and radiological testing. There is no doubt that the COVID-19 experience when handling diabetic foot problems will likely transform our approach to the management of diabetic foot disease especially in the areas of digital health and smart technology. Full article

(This article belongs to the Special Issue The Diabetic Foot: Recent Advances and Future Developments)

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