Two-year incidence and risk factors of diabetic foot ulcer: second phase report of Ahvaz diabetic foot cohort (ADFC) study.

AIM/INTRODUCTION: This study was designed as the second phase of a prospective cohort study to evaluate the incidence and risk factors of diabetic foot ulcers (DFU). MATERIALS AND METHODS: The study was conducted in a university hospital in Iran. Each participant was checked and followed up for two years in terms of developing newfound DFU as ultimate outcome. We investigated the variables using univariate analysis and then by backward elimination multiple logistic regression. RESULTS: We followed up 901 eligible patients with diabetes for two years. The mean age of the participants was 53.24 ± 11.46 years, and 58.53% of them were female. The two-year cumulative incidence of diabetic foot ulcer was 8% (95% CI 0.071, 0.089) [Incidence rate: 49.9 /1000 person-years]. However, the second-year incidence which was coincident with the COVID-19 pandemic was higher than the first-year incidence (4.18% and 1.8%, respectively). Based on our analysis, the following variables were the main risk factors for DFU incidence: former history of DFU or amputation [OR = 76.5, 95% CI(33.45,174.97), P value < 0.001], ill-fitting foot-wear [OR = 10.38, 95% CI(4.47,24.12), P value < 0.001], smoking [OR = 3.87,95%CI(1.28, 11.71),P value = 0.016], lack of preventive foot care [OR = 2.91%CI(1.02,8.29),P value = 0.045], and insufficient physical activity[OR = 2.25,95% CI(0.95,5.35),P value = 0.066]. CONCLUSION: Overall, the two-year cumulative incidence of diabetic foot ulcer was 8% [Incidence rate: 49.9 /1000 person-years]; however, the second-year incidence was higher than the first-year incidence which was coincident with the COVID-19 pandemic (4.18% and 1.8%, respectively). Independent risk factors of DFU occurrence were prior history of DFU or amputation, ill-fitting footwear, smoking, lack of preventive foot care, and insufficient physical activity.

The unique multidisciplinarity of diabetes-related foot disease.

Few diseases globally require treatment from so many different disciplines as diabetes-related foot disease. At least 25 different professionals may be involved: casting technicians, dermatologists, diabetes (educator) nurses, diabetologists, dieticians, endocrinologists, general practitioners, human movement scientists, infectious diseases experts, microbiologists, nuclear medicine physicians, orthopaedic surgeons, orthotists, pedorthists, physical therapists, plastic surgeons, podiatric surgeons, podiatrists, prosthetists, psychologists, radiologists, social workers, tissue viability physicians, vascular surgeons, and wound care nurses. A shared vocabulary and shared treatment goals and recommendations are then essential. The International Working Group on the Diabetic Foot (IWGDF) has produced guidelines and supporting documents to stimulate and support shared and multidisciplinary evidence-based treatment in diabetes-related foot disease. In this special virtual issue of Diabetes/Metabolism Research and Reviews, all 21 documents of the 2023 update of the IWGDF Guidelines are bundled, added with a further 6 reviews from multidisciplinary experts to drive future research and clinical innovations, based on their contributions to the International Symposium on the Diabetic Foot. We hope the readers will enjoy this special virtual issue, and widely implement the knowledge shared here in their daily clinical practice and research endeavours with the goal to improve the care for people with diabetes-related foot disease.

Pedal medial arterial calcification in diabetic foot ulcers: A significant risk factor of amputation and mortality.

AIMS: Pedal medial arterial calcification (MAC) is frequently observed in individuals with diabetic foot ulcers (DFUs). However, the impact of pedal MAC on individuals with DFUs remains uncertain. The main aim of this study was to evaluate the association between pedal MAC with amputation and mortality outcomes. METHODS: A prospective, observational cohort study was conducted at West China Hospital from January 2012 to December 2021. Logistic regression analyses, Kaplan-Meier survival method, and Cox proportional hazards models were employed to evaluate the relationship between pedal MAC and amputation as well as mortality. RESULTS: A total of 979 patients were enrolled in the study. Peripheral artery disease (PAD) was observed in 53% of patients with DFUs, and pedal MAC was found in 8%. Over a median follow-up of 46 (23-72) months, foot amputation was performed on 190 patients, and mortality occurred in 246 patients. Pedal MAC showed a significant association with amputation both in unadjusted analysis (odds ratio [OR] = 2.98, 95% confidence interval [CI] = 1.86-4.76, p < .001) and after adjusting sex, age, albumin levels, hemoglobin levels, and diabetic retinopathy status (OR 2.29, 95% CI 1.33-3.93, p = .003). The risk of amputation was found to be twofold higher in individuals with PAD and pedal MAC compared to those with PAD alone (OR 2.05, 95% CI 1.10-3.82, p = .024). Furthermore, the presence of pedal MAC was significantly associated with an increased risk of mortality (p = .005), particularly among individuals with DFUs but without PAD (HR 4.26, 95% CI 1.90-9.52, p < .001), rather than in individuals presenting with both DFUs and PAD. CONCLUSION: The presence of pedal MAC is significantly associated with both amputation and mortality in individuals with DFUs. Moreover, pedal MAC could provide additional value to predict amputation other than PAD.

Evaluation of usability, adherence, and clinical efficacy of therapeutic footwear in persons with diabetes at moderate to high risk of diabetic foot ulcers: A multicenter prospective study.

OBJECTIVE: To evaluate therapeutic footwear expectations and usability of individuals with diabetes and foot complications. DESIGN: A prospective multicenter study was conducted on participants with a high risk of developing a diabetic foot ulcer. SETTING: Participants were enrolled in 11 different specialized diabetic foot units in Spain between March 2022 and June 2023. SUBJECTS: Patients with diabetes at moderate to high risk of foot ulceration receiving first therapeutic footwear prescription. INTERVENTIONS: All the patients included in the research were prescribed with their first pair of therapeutic footwear. MAIN MEASURES: Primary outcome measures were MOS-pre and MOS-post questionnaires evaluating use and usability of prescribed therapeutic footwear. Secondary outcome measures aimed to evaluate footwear clinical efficacy as ulceration rate and self-reported perceived walking distance per day. RESULTS: The use of therapeutic footwear exceeded the patient's pre-provision prediction of their anticipated use in 94% of people (n = 126). Based on the visual analogic satisfaction scale, the median satisfaction of daily wearing their therapeutic footwear was 7 points, Interquartile Range (IQR) [5-8.25]. During the follow-up period, 39 participants (29.1%) experienced diabetic foot ulcer. Perceived walking distance participants reported an improvement in their perceived walking ability during various daily life activities. CONCLUSIONS: Diabetes patients at moderate to high risk of diabetic foot ulcer improved their perception of walking ability after therapeutic footwear prescription. Adherence to the therapeutic footwear prescription resulted in less ulcerations.

Diabetic foot ulcers risk prediction in patients with type 2 diabetes using classifier based on associations rule mining.

Identifying diabetic patients at risk of developing foot ulcers, as one of the most significant complications of diabetes, is a crucial healthcare concern. This study aimed to develop an associative classification model (CBA) using the Apriori algorithm to predict diabetic foot ulcers (DFU). This retrospective cohort study included 666 patients with type 2 diabetes referred to Shahid Beheshti Hospital in Iran between April 2020 and August 2022, of which 279 (42%) had DFU. Data on 29 specific baseline features were collected, which were preprocessed by discretizing numerical variables based on medical cutoffs. The target variable was the occurrence of DFU, and the minimum support, confidence, and lift thresholds were set to 0.01, 0.7, and 1, respectively. After data preparation and cleaning, a CBA model was created using the Apriori algorithm, with 80% of the data used as a training set and 20% as a testing set. The accuracy and AUC (area under the roc curve) measure were used to evaluate the performance of the model. The CBA model discovered a total of 146 rules for two patient groups. Several factors, such as longer duration of diabetes over 10 years, insulin therapy, male sex, older age, smoking, addiction to other drugs, family history of diabetes, higher body mass index, physical inactivity, and diabetes complications such as proliferative and non-proliferative retinopathy and nephropathy, were identified as major risk factors contributing to the development of DFU. The CBA model achieved an overall accuracy of 96%. Also, the AUC value was 0.962 (95%CI 0.924, 1.000). The developed model has a high accuracy in predicting the risk of DFU in patients with type 2 diabetes. The creation of accurate predictive models for DFU has the potential to significantly reduce the burden of managing recurring ulcers and the need for amputation, which are significant health concerns associated with diabetes.

The 10-year follow-up of a community-based cohort of people with diabetes: The incidence of foot ulceration and death.

BACKGROUND: Identifying people with diabetes who are likely to experience a foot ulcer is an important part of preventative care. Many cohort studies report predictive models for foot ulcerations and for people with diabetes, but reports of long-term outcomes are scarce. AIM: We aimed to develop a predictive model for foot ulceration in diabetes using a range of potential risk factors with a follow-up of 10 years after recruitment. A new foot ulceration was the outcome of interest and death was the secondary outcome of interest. DESIGN: A 10-year follow-up cohort study. METHODS: 1193 people with a diagnosis of diabetes who took part in a study in 2006-2007 were invited to participate in a 10-year follow-up. We developed a prognostic model for the incidence of incident foot ulcerations using a survival analysis, Cox proportional hazards model. We also utilised survival analysis Kaplan-Meier curves, and relevant tests, to assess the association between the predictor variables for foot ulceration and death. RESULTS: At 10-year follow-up, 41% of the original study population had died and more than 18% had developed a foot ulcer. The predictive factors for foot ulceration were an inability to feel a 10 g monofilament or vibration from a tuning fork, previous foot ulceration and duration of diabetes. CONCLUSIONS: The prognostic model shows an increased risk of ulceration for those with previous history of foot ulcerations, insensitivity to a 10 g monofilament, a tuning fork and duration of diabetes. The incidence of foot ulceration at 10-year follow-up was 18%; however, the risk of death for this community-based population was far greater than the risk of foot ulceration.

Risk factors of foot ulcers in patients with end-stage renal disease on dialysis: A meta-analysis.

The present study aims to assess the risk factors for foot ulcers in patients undergoing dialysis for end-stage renal disease (ESRD) and to provide evidence-based guidance for prevention and treatment. A systematic search was conducted on PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Data from the database inception until May 2023 to identify relevant studies investigating the risk factors for foot ulcers in dialysis patients with ESRD. Two independent researchers conducted the literature screening and data extraction. The meta-analysis was performed using STATA 17.0 software. Ultimately, six articles comprising 1620 patients were included for analysis. The meta-analysis revealed that male (OR, 1.464; 95% CI: 1.082-1.980, p = 0.013), hypertension (OR, 1.781; 95% CI: 1.293-2.4550, p < 0.001), peripheral artery disease (PAD) (OR, 5.014; 95% CI: 2.514-9.998, p < 0.001), type 1 diabetes mellitus (T1DM) (OR, 2.993; 95% CI: 1.477-6.065, p = 0.002) and type 2 diabetes mellitus (T2DM) (OR, 2.498; 95% CI:1.466-4.256, p = 0.001) were risk factors for foot ulcers in dialysis patients with ESRD. Conversely, the female sex (OR, 0.683; 95% CI: 0.505-0.924, p = 0.013) was a protective factor against foot ulcers. Our analysis revealed that male sex, hypertension, PAD, T1DM and T2DM were risk factors for foot ulcers in patients undergoing dialysis for ESRD. Conversely, the female sex was a protective factor against foot ulcers. Therefore, it is crucial to strengthen health education that targets patients with these risk factors and regularly screen high-risk individuals. Early detection and treatment can help delay disease progression.

Metabolic dysfunction-associated fatty liver disease in the elderly with diabetic foot ulcers: A longitudinal cohort study.

This study aimed to explore the association between metabolic-associated fatty liver disease (MAFLD) and ulcer recurrence risk in patients with diabetic foot ulcers (DFUs) through an ambispective longitudinal cohort. From December 2013 to December 2022, a total of 482 inpatients with DFUs (PEDIS grade 3 and above with a severe infection) were eligible for inclusion in this study. This was an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 36 months. According to whether having MAFLD or not, all subjects were placed into two groups: non-MAFLD (n = 351) and MAFLD (n = 131). The association between MAFLD and ulcer recurrence in patients with DFUs was then evaluated through multivariate Cox regression analysis, stratified analyses and Kaplan-Meier survival analysis. Throughout the follow-up period, out of 482 subjects with DFUs, 68 had ulcer recurrence (14.1%). Three Cox regression models were established for data analyses. In the model I (unadjusted), MAFLD was significantly associated with the ulcer recurrence rate in patients with DFUs (HR = 1.79; 95% CI = 1.097-2.92; p = 0.02). Model II (adjusted model I with gender and age) (HR = 1.781; 95% CI = 1.09-2.912; p = 0.021) and model III (adjusted model II with CVD, duration of diabetes and Cr.) (HR = 1.743; 95% CI = 1.065-2.855; p = 0.027) also showed that MAFLD was significantly related to the ulcer recurrence risk in patients with DFUs, respectively. Stratified analysis indicated that subjects aged ≥60 had a greater risk of ulcer recurrence in MAFLD than in non-MAFLD (HR = 2.31; 95% CI = 1.268-4.206; p = 0.006). Kaplan-Meier survival curve analysis showed that ulcer recurrence rate had a significant association with MAFLD (log-rank, p = 0.018). This study indicated a close association between ulcer recurrence risk and MAFLD in patients with DFUs, especially in the elderly (aged ≥60). Therefore, special attention should be paid to the elderly with both DFUs and MAFLD because they have a higher ulcer recurrence rate than other general populations in routine clinical practice.

Cell Therapy of Vascular and Neuropathic Complications of Diabetes: Can We Avoid Limb Amputation?

Globally, a leg is amputated approximately every 30 seconds, with an estimated 85 percent of these amputations being attributed to complications arising from diabetic foot ulcers (DFU), as stated by the American Diabetes Association. Peripheral arterial disease (PAD) is a risk factor resulting in DFU and can, either independently or in conjunction with diabetes, lead to recurring, slow-healing ulcers and amputations. According to guidelines amputation is the recommended treatment for patients with no-option critical ischemia of the limb (CTLI). In this article we propose cell therapy as an alternative strategy for those patients. We also suggest the optimal time-frame for an effective therapy, such as implanting autologous mononuclear cells (MNCs), autologous and allogeneic mesenchymal stromal cells (MSC) as these treatments induce neuropathy relief, regeneration of the blood vessels and tissues, with accelerated ulcer healing, with no serious side effects, proving that advanced therapy medicinal product (ATMPs) application is safe and effective and, hence, can significantly prevent limb amputation.

What Are Diabetic Foot Ulcers?

This JAMA Patient Page describes diabetic foot ulcers and their evaluation and treatment.

More new cancers in type 2 diabetes with diabetic foot disease: A longitudinal observational study.

OBJECTIVE: Cancer has been proposed as the primary cause of death in type 2 diabetes (T2D). The life expectancy is reduced after a diabetic foot ulcer. We investigated whether Diabetic Foot Disease related to an increased risk of developing a new cancer. RESEARCH DESIGN AND METHODS: We conducted a retrospective analysis on a cohort of patients hospitalized for T2D between 2009 and 2017, stratified for the risk of diabetic foot ulcer (International Working Group on Diabetic Foot classification). We highlighted new cancers in their medical records until December 2020. The relationship between Diabetic Foot Disease and later cancers was analyzed by multivariable Cox regression and survival curves were compared. RESULTS: Among 519 patients, 27% had a Diabetic Foot Disease, and 159 were classified as grades 1 or 2 (at risk). As compared to the 218 patients graded 0 according to the IWGDF, they were more men, older, with a longer duration of diabetes, more vascular complications, a greater incidence of insulin use, and a higher skin autofluorescence. During the 54 months of follow-up, 63 (12.1%) new cancers were diagnosed. Baseline Diabetic Foot Disease was significantly associated with a higher risk of cancer (multivariable adjusted Hazard ratio: 2.08, 95%CI: 1.02-4.25), whereas the relation was not significant for subjects at risk of DFU (HR: 1.65, 95%CI:0.81-3.35) CONCLUSION: The risk of cancer was increased twofold in T2D with Diabetic Foot Disease.

[Evaluation of tissue perfusion by indocyanine green fluorescein angiography in patients with neuroischemic diabetic foot syndrome after endovascular treatment]. / Otsenka tkanevoi perfuzii metodom fluorestsentnoi angiografii s indotsianinom zelenym u patsientov s neiroishemicheskoi formoi sindroma diabeticheskoi stopy posle endovaskulyarnogo lecheniya.

OBJECTIVE: To evaluate the fluorescence angiography (FA) parameters with Indocyanine green (ICG) and their dynamics in diabetic foot patients after endovascular treatment. MATERIAL AND METHODS: A single-center prospective non-blinded study was conducted with the inclusion of 47 diabetic foot patients with Chronic limb-threatening ischemia (CLTI). TcPO2 and FA-ICG were done before and after angioplasty. Zones of interest were selected for FA-ICG: the area of minimum and maximum fluorescence, the area of of the largest part of the foot. Also presented are the parameters of FA ICG: Tstart (sec) - the time of occurrence of min fluorescence (Istart, unit) in the zone of interest after the introduction of ICG; Tmax (sec) - the time to achieve max fluorescence (Imax, unit) after the introduction of ICG; Tmax -Tstart (sec) - the difference in the time of reaching Imax and Istart. RESULTS: The median TcPO2 values indicated the presence of CLTI before revascularization. Technical success of revascularization was achieved in 45 patients. In the postoperative period, statistically significant changes in TcPO2 and Tstart, Tmax, Tmax-Tstar were obtained. A reduction in the time to reach the ICZ to the zones of interest was noted. CONCLUSION: FA-ICG evaluate the visual and quantitative characteristics of perfusion of soft tissues of the foot. Reducing the time to reach the fluorescent substance in the areas of interest makes it possible to assume the restoration of the main blood flow to the foot. Further investigations are warranted to determine threshold values to predict wound healing and indications for revascularization.

Objectively assessed long-term wearing patterns and predictors of wearing orthopaedic footwear in people with diabetes at moderate-to-high risk of foot ulceration: a 12 months observational study.

BACKGROUND: Orthopaedic footwear can only be effective in preventing diabetic foot ulcers if worn by the patient. Robust data on long-term wearing time of orthopaedic footwear are not available, and needed to gain more insights into wearing patterns and associated factors (i.e. participants' demographic, disease-related characteristics, and footwear usability). We aimed to objectively assess long-term wearing patterns and identify factors associated with wearing orthopaedic footwear in people with diabetes at moderate-to-high risk of ulceration. METHODS: People diagnosed with diabetes mellitus type 1 and 2 with loss of protective sensation and/or peripheral artery disease and prescribed with orthopaedic footwear were included and followed for 12 months. The primary outcome was mean daily wearing time, continuously measured using a temperature sensor inside the footwear (Orthotimer®). Adherence to wearing orthopaedic footwear was calculated as percentage of wearing time of a total assumed 16 h out-of-bed daytime, where adherence < 60% was a pre-determined non-adherent threshold. Wearing time patterns were assessed by calculating participants' wearing (in)consistency. One-way analyses of variance tested for wearing time differences between subgroups, weekdays, and weekend days. Factors potentially associated with wearing time were collected by questionnaires and medical files. Univariately associated factors were included in multivariate linear regression analysis. RESULTS: Sixty one participants were included (mean (SD) age: 68.0 (7.4) years; females: n = 17; type 2 diabetes mellitus: n = 54). Mean (SD) overall daily wearing time was 8.3 (6.1) hours/day. A total of 40 (66%) participants were non-adherent. Participants with a consistent wearing pattern showed higher daily wearing times than participants with an inconsistent pattern. Mean (SD) wearing times were 12.7 (4.3) vs 3.6 (4.8) hours/day, respectively (P < 0.001). Mean (SD) wearing time was significantly higher (P < 0.010) during weekdays (8.7 (6.0) hours/day) compared to Saturday (8.0 (6.1) hours/day) and Sunday (6.9 (6.2) hours/day). In the multivariate model (R2 = 0.28), "satisfaction with my wear of orthopaedic footwear" was positively associated (P < 0.001) with wearing time. The other seven multivariate model factors (four demographic variables and three footwear usability variables) were not associated with wearing time. CONCLUSIONS: Only one out of three people at moderate to high risk of foot ulceration were sufficiently adherent to wearing their orthopaedic footwear. Changing people's wearing behaviour to a more stable pattern seems a potential avenue to improve long-term adherence to wearing orthopaedic footwear. Investigated factors are not associated with daily wearing time. Based on these factors the daily wearing time cannot be estimated in daily practice. TRIAL REGISTRATION: Netherlands Trial Register NL7710. Registered: 6 May 2019.

Prevalence of diabetes foot ulcers and associated factors among adult diabetic patients in three referral hospitals in Mogadishu, Somalia.

Background: Diabetes mellitus (DM) causes significant morbidity and mortality in sub-Saharan Africa (SSA), including Somalia. Among diabetic patients, diabetic foot ulcers (DFUs) constitute the largest proportion of admissions, amputations, and mortality. The aim of this study is to assess the prevalence of diabetic foot ulcers and subsequently determine factors associated with it among diabetic patients at three major hospitals in Somalia. Methods: An institutional-based cross-sectional study was conducted among 193 diabetic patients between August and November 2022. All eligible diabetes patients who were attending De Martini Hospital, Madina General Hospital, and Deynile General Hospital during the study period were included in the study. Patients were interviewed using a structured questionnaire. We collected demographic, clinical, and behavioral variables from all participants. A bivariate and multivariable logistic regression model was fitted to identify factors associated with diabetic foot ulcer. An odds ratio with a 95% confidence interval was computed to determine the level of significance. Result: The mean age of the study's participants was 50.9 ± 13.6 years. The prevalence of diabetic foot ulcer was 15%. Patients who were either overweight or obese (OR 4.63, CI: 2.08-10.30), had a lack of family support in managing diabetes (OR 3.33, CI: 1.74-6.36), and did not check their feet regularly were more likely to develop DFU (OR 1.99, CI:1.08-3.66). Conclusion: Increased body mass index, lack of family support, and not checking feet regularly were associated with DFUs. The high prevalence of DFUs and the plethora of needs of people with DFUs pose challenges for health care. A coordinated health care system is necessary to meet the needs of diabetic patients and prevent DFUs.

Use of the SINBAD score as a predicting tool for major adverse foot events in patients with diabetic foot ulcer: A French multicentre study.

OBJECTIVE: To assess the relationship between the site, ischaemia, neuropathy, bacterial infection, area, depth (SINBAD) score and major adverse foot events in patients with diabetes and foot ulcers. METHODS: For this retrospective ancillary study, patients (n = 537) followed for a diabetic foot ulcer (DFU) in six French hospitals were included between 1 February 2019 and 17 March 2019, and between 1 February 2020 and 17 March 2020. The SINBAD score was assessed at inclusion. The frequency of a composite outcome consisting of eight major adverse foot events (MAFE) was assessed after 5-6 months of follow-up: hospitalisation for DFU, septic surgery, revascularisation, minor amputation, major amputation, death, secondary infection and ulcer recurrence. A logistical regression explored the link between the SINBAD score and MAFE and each of its component. RESULTS: A low SINBAD score (from 0 to 3) was observed in 61% of patients and a high (from 4 to 6) in 39%. MAFE occurred in, respectively, 24% and 28% of these patients. Multivariate analyses showed a significant relationship between the SINBAD score and MAFE, with the continuous SINBAD score: odds ratio (OR) 1.72 [95% CI (1.51-1.97)] or dichotomic SINBAD score (values: 0-3 and 4-6): OR 3.71 [95% CI (2.54-5.42)]. The SINBAD score (continuous or dichotomic) at inclusion was also significantly associated with six out of the eight components of the MAFE. CONCLUSIONS: The SINBAD score is a useful tool for predicting major adverse foot events.

The effectiveness of a thermography-driven preventive foot care protocol on the recurrence of diabetic foot ulcers in low-medical resource settings: An open-labeled randomized controlled trial.

BACKGROUND: Plantar temperature monitoring, along with a comprehensive preventive foot care approach, is utilized to prevent recurrence of diabetic foot ulcers. However, there is a lack of standardized protocols for individuals with diabetic foot ulcer history in low-medical resource countries. OBJECTIVE: This study investigated the efficacy of nurse-led, thermographic-evaluation-guided foot care in preventing diabetic foot ulcer recurrence in a low-medical resource country. DESIGN: Single-blind, 1:1 allocation randomized controlled trial. SETTINGS: Two wound care facilities with wound care nurse specialists in Indonesia. PARTICIPANTS: 120 patients with a diabetic foot ulcer history. INTERVENTION: In the intervention group, baseline risk assessment including smartphone thermography evaluation was performed. Personalized foot care and education were conducted monthly for participants whose thermographs showed increased foot lesion temperature at baseline risk assessment. The control group received usual care and education using a booklet at baseline. The follow-up period was six months. MAIN OUTCOME: Time to recurrence was evaluated using Kaplan-Meier survival analysis, and between-group comparisons were performed using the log-rank test. Potential risk factors were incorporated into the multivariate Cox regression model. Secondary outcomes included quality of life (European Quality of Life 5 Dimensions 3 Level Version) and foot care behavior, were analyzed using Mixed Models for Repeated Measures at baseline, third, and sixth follow-up (3 and 6 months from baseline). RESULTS: 120 participants (intervention 60, control 60) were randomized. The intervention group had a significantly lower recurrence rate than the control group (15% vs. 35%, p = 0.011) and a significant difference in time to ulceration (log-rank test, p = 0.009) after a 6-month follow-up period. Intervention care reduced the risk of diabetic foot ulcer recurrence by 59% (Hazard ratio 0.41, 95% confidence interval 0.18, 0.96, p = 0.039) in multivariate Cox regression analysis. On the third follow-up, total diabetic foot care behavior score (p < 0.001) was significantly improved by the intervention. On the sixth follow-up, mobility (p = 0.020), self-care (p = 0.023), pain/discomfort (p < 0.001), anxiety/depression (p = 0.016), EuroQol Visual Analogue Scale score (p = 0.002), and total diabetic foot care behavior score (p < 0.001) showed significant improvements in the intervention group. CONCLUSIONS: Foot care and personalized education delivered at a frequency based on the risk level assessed by thermography effectively reduced diabetic foot ulcer recurrence, and improved quality of life and foot care behaviors. REGISTRATION NUMBER: UMIN000039012. TWEETABLE ABSTRACT: Nurse-led diabetic foot care and education reduced diabetic foot ulcer recurrence in Indonesia.

Non-classical monocytes frequency and serum vitamin D3 levels are linked to diabetic foot ulcer associated with peripheral artery disease.

AIMS/INTRODUCTION: Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D3 were implicated in DFUs associated with PAD. MATERIALS AND METHODS: There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme-linked immunosorbent assay. RESULTS: DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence. CONCLUSIONS: Non-classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk-reducing factor for PAD occurrence.

Development of the Italian clinical practice guidelines for the treatment of diabetic foot syndrome: design and methodological aspects.

AIMS: Diabetic foot syndrome (DFS) and its complications are a growing public health concern. The Italian Society of Diabetology (SID) and the Italian Association of Clinical Diabetologists (AMD), in collaboration with other scientific societies, will develop the first Italian guidelines for the treatment of DFS. METHODS: The creation of SID/AMD Guidelines is based on an extended work made by 19 panelists and 12 members of the Evidence Review Team. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology has been used to decide aims, reference population, and target health professionals. Clinical questions have been created using PICO (Patient, Intervention, Comparison, Outcome) conceptual framework. The definition of questions has been performed using a two-step web-based Delphi methodology, a structured technique aimed at obtaining by repeated rounds of questionnaires a consensus opinion from a panel of experts in areas wherein evidence is scarce or conflicting, and opinion is important. RESULTS: The mean age of panelists (26.3% women) was 53.7 ± 10.6 years. The panel proposed 34 questions. A consensus was immediately reached for all the proposed questions, 32 were approved and 2 were rejected. CONCLUSIONS: The areas covered by clinical questions included diagnosis of ischemia and infection, treatment of ischemic, neuropathic, and infected ulcers, prevention of foot ulceration, organization and education issues, and surgical management. The PICO presented in this paper are designed to provide indications for healthcare professionals in charge of diabetic foot treatment and prevention, primarily based on clinical needs of people with diabetic foot syndrome and considering the existing organization of health care.

Health Literacy predicts incident foot ulcers after 4 years - the SHELLED cohort study.

AIMS/HYPOTHESIS: To determine whether health literacy is associated with an index diabetes-related foot ulcer (DFU). METHODS: The SHELLED Study is a 4-year prospective study of people with diabetes aged over 40 with no history of DFU. The primary outcome was development of a first foot ulcer. Health Literacy was measured using the short form Test of Functional Health Literacy in Adults (s-TOFHLA) and nine domains of the Health Literacy Questionnaire (HLQ). RESULTS: Of 222 participants, 191 (86.0%) completed the study, of whom 13 (5.9%) developed an incident ulcer. In multivariable models, every unit increase in S-TOFHLA was associated with a reduced odds of foot ulcer development by 6% (OR 0.94, 95% CI 0.88 to 0.99). Better scores on two HLQ domains reduced the odds of foot ulcer (actively managing my health (OR 0.23, 95% CI 0.08 to 0.65) and understanding health information well enough to know what to do (OR 0.39, 95% CI 0.19 to 0.78). This was independent of baseline risk for foot disease. CONCLUSIONS/INTERPRETATION: These data provide novel evidence that health literacy is an important clinical risk factor for index foot ulceration. This is an area of potential focus for research and development of educational programs or policy aimed at reducing development of incident foot ulceration.

Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation.

Diabetic foot ulcer (DFU), a common intractable chronic complication of diabetes mellitus (DM), has a prevalence of up to 25%, with more than 17% of the affected patients at risk of amputation or even death. Vascular risk factors, including vascular stenosis or occlusion, dyslipidemia, impaired neurosensory and motor function, and skin infection caused by trauma, all increase the risk of DFU in patients with diabetes. Therefore, diabetic foot is not a single pathogenesis. Preclinical studies have contributed greatly to the pathogenesis determination and efficacy evaluation of DFU. Many therapeutic tools are currently being investigated using DFU animal models for effective clinical translation. However, preclinical animal models that completely mimic the pathogenesis of DFU remain unexplored. Therefore, in this review, the preparation methods and evaluation criteria of DFU animal models with three major pathological mechanisms: neuropathy, angiopathy and DFU infection were discussed in detail. And the advantages and disadvantages of various DFU animal models for clinical sign simulation. Furthermore, the current status of vitro models of DFU and some preclinical studies have been transformed into clinical treatment programs, such as medical dressings, growth factor therapy, 3D bioprinting and pre-vascularization, Traditional Chinese Medicine treatment. However, because of the complexity of the pathological mechanism of DFU, the clinical transformation of DFU model still faces many challenges. We need to further optimize the existing preclinical studies of DFU to provide an effective animal platform for the future study of pathophysiology and clinical treatment of DFU.