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Diabetic foot ulceration is a serious complication of diabetes mellitus worldwide and the most common cause of hospitalization in diabetic patients. The etiology of diabetic foot ulcerations is complex due to their multifactorial nature; in the pathophysiology of diabetic foot ulceration polyneuropathy is important. Proper adherence to standard treatment strategies and interdisciplinary cooperation can reduce the still high rates of major amputations.

Purpose of ReviewDiabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain, foot ulcers, and lower limb amputation. This review summarizes the epidemiology, risk factors, and management of diabetic peripheral neuropathy and related lower extremity complications.Recent FindingsThe prevalence of peripheral neuropathy is estimated to be between 6 and 51% among adults with diabetes depending on age, duration of diabetes, glucose control, and type 1 versus type 2 diabetes. The clinical manifestations are variable, ranging from asymptomatic to painful neuropathic symptoms. Because of the risk of foot ulcer (25%) and amputation associated with diabetic peripheral neuropathy, aggressive screening and treatment in the form of glycemic control, regular foot exams, and pain management are important. There is an emerging focus on lifestyle interventions including weight loss and physical activity as well.SummaryThe American Diabetes Association has issued multiple recommendation statements pertaining to diabetic neuropathies and the care of the diabetic foot. Given that approximately 50% of adults with diabetes will be affected by peripheral neuropathy in their lifetime, more diligent screening and management are important to reduce the complications and health care burden associated with the disease.

Aims/hypothesis Diabetic foot disease (DFD) is a leading cause of hospital admissions and amputations. Global trends in diabetes-related amputations have been previously reviewed, but trends in hospital admissions for multiple other DFD conditions have not. This review analysed the published incidence of hospital admissions for DFD conditions (ulceration, infection, peripheral artery disease [PAD], neuropathy) and diabetes-related amputations (minor and major) in nationally representative populations. Methods PubMed and Embase were searched for peer-reviewed publications between 1 January 2001 and 5 May 2022 using the terms ‘diabetes’, ‘DFD’, ‘amputation’, ‘incidence’ and ‘nation’. Search results were screened and publications reporting the incidence of hospital admissions for a DFD condition or a diabetes-related amputation among a population representative of a country were included. Key data were extracted from included publications and initial rates, end rates and relative trends over time summarised using medians (ranges). Results Of 2527 publications identified, 71 met the eligibility criteria, reporting admission rates for 27 countries (93% high-income countries). Of the included publications, 14 reported on DFD and 66 reported on amputation (nine reported both). The median (range) incidence of admissions per 1000 person-years with diabetes was 16.3 (8.4–36.6) for DFD conditions (5.1 [1.3–7.6] for ulceration; 5.6 [3.8–9.0] for infection; 2.5 [0.9–3.1] for PAD) and 3.1 (1.4–10.3) for amputations (1.2 [0.2–4.2] for major; 1.6 [0.3–4.3] for minor). The proportions of the reported populations with decreasing, stable and increasing admission trends were 80%, 20% and 0% for DFD conditions (50%, 0% and 50% for ulceration; 50%, 17% and 33% for infection; 67%, 0% and 33% for PAD) and 80%, 7% and 13% for amputations (80%, 17% and 3% for major; 52%, 15% and 33% for minor), respectively. Conclusions/interpretation These findings suggest that hospital admission rates for all DFD conditions are considerably higher than those for amputations alone and, thus, the more common practice of reporting admission rates only for amputations may substantially underestimate the burden of DFD. While major amputation rates appear to be largely decreasing, this is not the case for hospital admissions for DFD conditions or minor amputation in many populations. However, true global conclusions are limited because of a lack of consistent definitions used to identify admission rates for DFD conditions and amputations, alongside a lack of data from low- and middle-income countries. We recommend that these areas are addressed in future studies. Registration This review was registered in the Open Science Framework database ( https://doi.org/10.17605/OSF.IO/4TZFJ ). Graphical abstract

Background Diabetic foot ulcers are a common complication of poorly controlled diabetes and often become infected, termed diabetic foot infection. There have been numerous studies of the microbiology of diabetic foot infection but no meta-analysis has provided a global overview of these data. This meta-analysis aimed to investigate the prevalence of bacteria isolated from diabetic foot infections using studies of any design which reported diabetic foot infection culture results. Methods The Medline, EMBASE, Web of Science and BIOSIS electronic databases were searched for studies published up to 2019 which contained microbiological culture results from at least 10 diabetic foot infection patients. Two authors independently assessed study eligibility and extracted the data. The main outcome was the prevalence of each bacterial genera or species. Results A total of 112 studies were included, representing 16,159 patients from which 22,198 microbial isolates were obtained. The organism most commonly identified was Staphylococcus aureus , of which 18.0% (95% CI 13.8–22.6%; I 2  = 93.8% [93.0–94.5%]) was MRSA. Other highly prevalent organisms were Pseudomonas spp., E. coli and Enterococcus spp. A correlation was identified between Gross National Income and the prevalence of Gram positive or negative organisms in diabetic foot infections. Conclusion The microbiology of diabetic foot infections is diverse, but S. aureus predominates. The correlation between the prevalence of Gram positive and negative organisms and Gross National Income could reflect differences in healthcare provision and sanitation. This meta-analysis has synthesised multiple datasets to provide a global overview of the microbiology of diabetic foot infections that will help direct the development of novel therapeutics.

Diabetic foot ulcer (DFU) is a common cause of admission in patients with diabetes. Diabetes increases the likelihood of inpatient Major Adverse Cardiovascular Events (MACE), and the presence of polyvascular disease (PD), defined by the presence of atherosclerosis in two or more arterial beds, further amplifies this risk. We assessed the impact of PD on outcomes in patients admitted due to a DFU. In this retrospective single-center study, we enrolled adult patients admitted to the diabetic foot unit between 2014 and 2019. The primary outcome was a composite of inpatient MACE or death. Secondary outcomes included amputations, leg revascularization, duration of admission and 1-year mortality. We additionally collected survival data till the end of 2023. A total of 537 patients were enrolled in the study, 264 suffering of PD. The primary endpoint occurred in 12.5 % and 4.4 % of patients with vs. without PD (p = 0.001). Patients with PD had an increased incidence of vascular interventions (42 % vs. 19.4 %, p < 0.001), any amputation (67.4 % vs. 48.4 %, p < 0.001) and major amputation (35.6 % vs. 13.2 %, p < 0.001). They had longer admissions (median 19 vs. 17 days, p = 0.002) and higher 1-year mortality rates (33.0 % vs. 12.1 %, p < 0.001). During 10-year follow up (median 3.3 years) median survival was 2.0 vs. 5.9 years for patients with vs. without PD (p < 0.001). PD in patients admitted with a DFU is associated with poor inpatient and long-term outcomes. This highlights the need for comprehensive risk assessment, optimization of in-patient management and long-term control of cardiovascular risk factors. •Nearly half of the patients admitted due to an acute diabetic foot ulcer suffer of polyvascular disease (PD).•Patients with PD have poor outcomes - higher risk of inpatient major adverse cardiovascular event, amputation or death.•Long-term survival of PD patients is markedly low with median survival of 2.0 years vs. 5.9 years in patients with no PD.•Guideline directed medical therapy should be offered to these patients aiming to improve these grim outcomes.

Background In 2007, we reported a summary of data comparing diabetic foot complications to cancer. The purpose of this brief report was to refresh this with the best available data as they currently exist. Since that time, more reports have emerged both on cancer mortality and mortality associated with diabetic foot ulcer (DFU), Charcot arthropathy, and diabetes-associated lower extremity amputation. Methods We collected data reporting 5-year mortality from studies published following 2007 and calculated a pooled mean. We evaluated data from DFU, Charcot arthropathy and lower extremity amputation. We dichotomized high and low amputation as proximal and distal to the ankle, respectively. This was compared with cancer mortality as reported by the American Cancer Society and the National Cancer Institute. Results Five year mortality for Charcot, DFU, minor and major amputations were 29.0, 30.5, 46.2 and 56.6%, respectively. This is compared to 9.0% for breast cancer and 80.0% for lung cancer. 5 year pooled mortality for all reported cancer was 31.0%. Direct costs of care for diabetes in general was $237 billion in 2017. This is compared to $80 billion for cancer in 2015. As up to one-third of the direct costs of care for diabetes may be attributed to the lower extremity, these are also readily comparable. Conclusion Diabetic lower extremity complications remain enormously burdensome. Most notably, DFU and LEA appear to be more than just a marker of poor health. They are independent risk factors associated with premature death. While advances continue to improve outcomes of care for people with DFU and amputation, efforts should be directed at primary prevention as well as those for patients in diabetic foot ulcer remission to maximize ulcer-free, hospital-free and activity-rich days.

ObjectiveTo assess the risk of diabetic foot ulcer (DFU) and find out its associated factors among subjects with type 2 diabetes (T2D) of Bangladesh.Design, setting and participantsThis cross-sectional study recruited 1200 subjects with T2D who visited 16 centres of Health Care Development Project run by Diabetic Association of Bangladesh.Primary and secondary outcome measuresRisk of DFU was assessed using a modified version of International Working Group on the Diabetic Foot (IWGDF) Risk Classification System. The modified system was based on five parameters, namely peripheral neuropathy (PN), peripheral arterial diseases (PAD), deformity, ulcer history and amputation. The risks were categorised as group 0 (no PN, no PAD), group 1 (PN, no PAD and no deformity), group 2A (PN and deformity, no PAD), group 2B (PAD), group 3A (ulcer history) and group 3B (amputation). The associated factors of DFU risk were determined using multinomial logistic regression for each risk category separately.ResultsOverall, 44.5% of the subjects were found ‘at risk’ of DFU. This risk was higher among men (45.6%) than women and among those who lived in rural areas (45.5%) as compared with the urban population. According to IWGDF categories, the risk was distributed as 55.5%, 4.2%, 11.6%, 0.3%, 20.6% and 7.9% for group 0, group 1, group 2A, group 2B, group 3A and group 3B, respectively. The associated factors of DFU (OR >1) were age ≥50 years, rural area, low economic status, insulin use, history of trauma, diabetic retinopathy and diabetic nephropathy.ConclusionA significant number of the subjects with T2D under study were at risk of DFU, which demands an effective screening programme to reduce DFU-related morbidity and mortality.

Therapeutic footwear becomes the first treatment line in the prevention of diabetic foot ulcer and future complications of diabetes. Previous studies and the International Working Group on the Diabetic Foot have described therapeutic footwear as a protective factor to reduce the risk of re-ulceration. In this study, we aimed to analyze the efficacy of a rigid rocker sole to reduce the recurrence rate of plantar ulcers in patients with diabetic foot. Between June 2016 and December 2017, we conducted a randomized controlled trial in a specialized diabetic foot unit. Fifty-one patients with diabetic neuropathy who had a recently healed plantar ulcer were randomized consecutively into the following two groups: therapeutic footwear with semi-rigid sole (control) or therapeutic footwear with a rigid rocker sole (experimental). All patients included in the study were followed up for 6 months (one visit each 30 ± 2 days) or until the development of a recurrence event. Primary outcome measure was recurrence of ulcers in the plantar aspect of the foot. A total of 51 patients were randomized to the control and experimental groups. The median follow-up time was 26 [IQR-4.4-26.1] weeks for both groups. On an intention-to-treat basis, 16 (64%) and 6 (23%) patients in the control and experimental groups had ulcer recurrence, respectively. Among the group with >60% adherence to therapeutic footwear, multivariate analysis showed that the rigid rocker sole improved ulcer recurrence-free survival time in diabetes patients with polyneuropathy and DFU history (P = 0.019; 95% confidence interval, 0.086-0.807; hazard ratio, 0.263). We recommend the use of therapeutic footwear with a rigid rocker sole in patients with diabetes with polyneuropathy and history of diabetic foot ulcer to reduce the risk of plantar ulcer recurrence. ClinicalTrials.gov NCT02995863.

Foot ulceration is the most common lower-extremity complication in patients with diabetes mellitus. This review considers the pathogenesis, treatment, and management of diabetic foot ulcers, including prevention of recurrence. Complications of diabetes that affect the lower extremities are common, complex, and costly. Foot ulceration is the most frequently recognized complication. In a community-based study in the northwestern United Kingdom, the prevalence of active foot ulcers identified at screening among persons with diabetes was 1.7%, and the annual incidence was 2.2%. 1 Higher annual incidence rates have been reported in specific populations: 6.0% among Medicare beneficiaries with diabetes, 5.0% among U.S. veterans with diabetes, and 6.3% in the global population of persons with diabetes. 2 – 4 On the basis of 2015 prevalence data from the International Diabetes Federation, 5 it is estimated that, . . .

We examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 ± 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-α, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs.