Diabetic Peripheral Arterial Disease Research Articles

One-Year Analysis of Autologous Peripheral Blood Mononuclear Cells as Adjuvant Therapy in Treatment of Diabetic Revascularizable Patients Affected by Chronic Limb-Threatening Ischemia: Real-World Data from Italian Registry ROTARI.

Wounds in diabetic patients with peripheral arterial disease (PAD) may be poorly responsive to revascularization and conventional therapies. Background/Objective: This study's objective is to analyze the results of regenerative cell therapy with peripheral blood mononuclear cells (PBMNCs) as an adjuvant to revascularization. Methods: This study is based on 168 patients treated with endovascular revascularization below the knee plus three PBMNC implants. The follow-up included clinical outcomes at 1-2-3-6 and 12 months based on amputations, wound healing, pain, and TcPO2. Results: The results at 1 year for 122 cases showed a limb rescue rate of 94.26%, a complete wound healing in 65.59% of patients, and an improvement in the wound area, significant pain relief, and increased peripheral oxygenation. In total, 64.51% of patients completely healed at 6 months, compared to the longer wound healing time reported in the literature in the same cohort of patients, suggesting that PBMNCs have an adjuvant effect in wound healing after revascularization. Conclusions: PBMNC regenerative therapy is a safe and promising treatment for diabetic PAD. In line with previous experiences, this registry shows improved healing in diabetic patients with below-the-knee arteriopathy. The findings support the use of this cell therapy and advocate for further research.

Association of Race With Referral Disparities for Patients With Diabetic Foot Ulcers at an Institution Serving Rural and Urban Populations.

Racial minorities are more likely to develop type 2 diabetes and experience associated microvascular complications. Non-Hispanic Blacks and Hispanics initially present with more severe diabetic foot ulcers (DFUs) and peripheral artery disease (PAD), with an associated 10-fold increase in risk for lower extremity amputation within the first year after diagnosis. This study was designed to determine if race is associated with a failure to refer to specialists for DFU treatment, and the severity of DFU at the time of initial presentation. Patients were identified from the medical record based on a diagnosis related to diabetic foot complications between January 1, 2018, and June 1, 2023, in the family medicine, endocrinology, orthopaedic, or emergency clinics at a Midwest Academic Hospital serving rural and urban populations. Patients self-reported race, demographics, severity of ulcer based on Wagner ulcer scale at time of referral, eventual amputation status, and measures of social determinants of health including the national Area Deprivation Index (ADI) and Rural-Urban Commuting Area (RUCA) codes were manually extracted and analyzed for correlations with referral status. A total of 597 patients were eligible for inclusion. Race was not associated with lower referral rates (P > .99) or source of referral (P = .58) to specialty clinic and ulcer severity at initial examination (P = .34). Patients who initially presented to the emergency department had more severe ulcers (P = .016), and higher severity was significantly associated with lower limb amputation vs mild ulcers (odds ratio = 38.8, P = .02). No significant differences in referral source or severity of ulcer at presentation were seen for sex, age, marital status, insurance type, rural status, ADI, time from referral to appointment, or eventual amputation. In this study, we found that patient race was not associated with severity of DFU at presentation or subsequent referral to a Midwest academic specialty orthopaedic clinic for care.Level of Evidence: Level III, retrospective review.

Optimizing ankle-brachial index measurement for peripheral arterial disease screening in mobile clinics

ObjectiveMultidisciplinary mobile clinics (MMCs) provide a robust venue to provide health care access and peripheral arterial disease (PAD) screening to underserved populations. The ankle-brachial index (ABI) can facilitate PAD diagnosis; however, traditional supine ABI measurements may be challenging technically in a mobile outreach clinic with limited infrastructure, whereas seated ABI offers technical ease. In this study, the usefulness and feasibility of performing supine ABI, seated ABI, and seated ABI with a calculation to account for seated hydrostatic pressure (seated-adjusted ABI) were compared in a mobile outreach setting. MethodsProspective data were collected from patients at five independent MMCs focused on diabetic foot and PAD screening with ABI for underserved communities. Three techniques were used to measure the ABI: seated ABI, seated-adjusted ABI using a formula to account for hydrostatic ankle pressure, and traditional supine ABI using a foldable massage table that is 5% of the cost of a medical stretcher. Comparative analysis was performed using the Student t test analysis and one-way analysis of variance. The frequency of completed seated ABI, seated-adjusted ABI, and supine ABI examinations performed at independent MMCs was quantified to determine feasibility. ResultsIn 166 individuals experiencing homelessness or housing instability who were screened over the course of five MMCs, 89 underwent PAD screening with ABI. Of the patients screened, 38 patients had seated, seated-adjusted, and supine ABIs measured (43% of total number of patients undergoing any ABI measurement). PAD (ABI < 0.9) was identified in one patient using all three ABI methods. Noncompressible ABI (ABI ≥ 1.3) were identified in 32 patients (32/38 [84%]) screened with seated ABI. Of these 32 patients, 24 (75%) continued to have noncompressible ABIs using seated-adjusted ABI. Of these 24 patients, 4 (17%) continued to have noncompressible ABI using supine ABI. The average seated ABI significantly differed from supine ABI (1.34 vs 1.14; P < .0001). The average seated ABI also significantly differed from seated-adjusted ABI (1.34 vs 1.29; P = .026). The average seated-adjusted ABI significantly differed from supine ABI (1.29 vs 1.14; P = .0204). ConclusionsWe found that seated and seated-adjusted ABI are grossly inaccurate and more often lead to falsely elevated noncompressible ABI (32/38 [84%] and 24/38 [75%], respectively) compared with supine ABI (6/38 [16%]). We recommend using supine ABI on patients for PAD screening. Supine measurement is technically feasible in outreach mobile clinics using a transportable folding massage table and is a more accurate tool for PAD screening.

Above-ankle Reamputation and Mortality following Transmetatarsal Amputation in Diabetic and Nondiabetic Peripheral Artery Disease

The risk of above-ankle reamputation following a transmetatarsal amputation is around 30%. Patient selection may be crucial to achieve good outcomes, and to avoid futile operations and suffering. We are aware of no previous comparison between the two largest patient groups that undergo lower extremity amputations: patients with diabetes, and patients with non-diabetic peripheral artery disease. Patients with diabetes or non-diabetic peripheral artery disease who had undergone a transmetatarsal amputation from 2004 through 2018 at our institution were included. Patient characteristics and peri-operative details were analyzed retrospectively. Subjects with diabetes were compared with subjects with non-diabetic peripheral artery disease regarding above-ankle reamputation, reamputation level, and mortality. Five-hundred-and-sixty transmetatarsal amputations in 513 subjects were included. The majority of transmetatarsal amputations (86%) occurred in diabetic subjects. Subjects with non-diabetic PAD had a higher risk of above-ankle reamputation (p = .008), and death (p < .001). At the time of data collection, only multiple-ray amputation (vs. single-ray) was an independent risk factor for above-ankle reamputation. Only age, medical comorbidity in general, and chronic heart failure were independent risk factors of death. To our knowledge, this study is the first to report marked differences in above-ankle reamputation rates and mortality following transmetatarsal amputation, comparing diabetics with non-diabetic patients with peripheral artery disease. However, the differences may be attributed to non-diabetics being older, having more medical comorbidities, and having more advanced foot ulcers at the time of transmetatarsal amputation. In patients exhibiting several of these risk factors, transmetatarsal amputation may be futile. Level of Clinical EvidencePrognostic Level 2: Retrospective study.

Diabetic peripheral arterial disease in COVID-19 pandemic.

Both diabetes and peripheral arterial disease (PAD) have complex interactions with COVID-19. PAD is one of the most important underlying factors in the development of diabetic foot. The COVID-19 pandemic has also caused an increase in cardiovascular complications in those with chronic diseases, including diabetics, due to both the thrombophilic course of the viral disease and the lockdown measures applied for prevention. Since both COVID-19 and diabetes mellitus predispose to thrombosis, PAD is likely to have a more severe course in diabetic patients with COVID-19. The aim of our study is to discuss the complications, prophylaxis, and treatment of PAD, which is a serious complication of diabetes, during the pandemic period.

Factors Determining Risk of Contralateral Lower Limb Amputations in Unilateral Dysvascular Transfemoral and Transtibial Amputees

Abstract Background: This study deals with the factors influencing contralateral lower limb amputations among unilateral dysvascular transfemoral and transtibial amputees. Aim: (1) Early identification of risk factors responsible for amputations in contralateral lower limb. (2) To determine the preventive measures of the concerned risk factors. (3) The aim of this study was to determine the risk factors associated with, contralateral amputation in patients with chronic limb threatening ischaemia (CLTI). Study Design: Cross-sectional study, 45 patients with unilateral transfemoral and transtibial amputees due to diabetes and peripheral arterial disease (PAD) were recruited for this study. Materials and Methods: Analysis of risk factors by ankle-brachial index (ABI), Claudication Pain Scale. Results: Unilateral transfemoral and transtibial amputees due to diabetic foot syndrome and PAD are at 2–4 times increased risk for contralateral lower-limb amputations. Conclusions: Risk of anticipated contralateral limb amputation is high based on ABI and Claudication Pain Scale. All patients, but particularly those at increased risk, should undergo close surveillance and counselling to help prevent subsequent amputations in their contralateral lower extremity.

Peripheral Arterial Disease in Diabetes and its Relation to Cardiovascular Risk Factors in Women

Objectives: Peripheral arterial disease (PAD) is characterized by occlusive disease in the abdominal aorta, iliac, and femoral arteries, leading to reduced blood flow and complications. Diabetes mellitus (DM) is known to contribute to the development and progression of PAD due to factors such as hyperglycemia, dyslipidemia, endothelial dysfunction, and inflammation. However, PAD may be underdiagnosed in women with DM, leading to adverse cardiovascular outcomes. The present study aimed to investigate the prevalence of PAD in women with type 2 DM (T2DM) and its relationship with cardiovascular risk factors. Materials and Methods: This hospital-based, cross-sectional, and observational study was conducted for a period of 3 months from June 10, 2023, to September 10, 2023, in the outpatient department of general medicine. After obtaining the approval from the Institutional Ethical Committee, the study was performed according to the Declarations of Helsinki and Good Clinical Practice requirements for human subject protection. Non-probability purposive sampling technique was used to enroll participants. Participants underwent face-to-face interviews and clinical examinations. Sociodemographic data, medical history, and pharmacotherapy details were collected. Laboratory investigations were conducted, including blood glucose, lipid profile, and glycosylated hemoglobin (HbA1C) tests. The ankle-brachial index (ABI) was measured. Results: The results showed that the majority of the participants were between 50 and 70 years of age, married, and had a high school education. Participants had an average body mass index (BMI) indicating overweight, and the average duration of diabetes was 6.571 years. Hypertension was the most prevalent comorbidity. Overweight, obesity I, and obesity II were present in 15.25% (n = 19), 33.6% (n = 42), and 8.8% (n = 11), respectively. Average values for HbA1C, fasting blood glucose (FBG), and postprandial blood glucose (PPBG) were within the diabetic range. ABI was normal in the right side, left side, and bilateral in 43.2%, 56%, and 14.4% of participants, respectively. ABI was borderline on the right side, left side, and bilateral in 40.8%, 36.8%, and 22.4% of participants, respectively. PAD was observed on the right side, left side, and bilateral in 16%, 7.2%, and 4% of participants, respectively. BMI, duration of DM, glycosylated hemoglobin, FBG, and PPBG showed significant negative correlations with ABI. Age, triglycerides, high-density lipoprotein, and low-density lipoprotein did not show any statistically significant correlation with ABI. Conclusion: The study highlighted the importance of screening for PAD in women with T2DM to improve cardiovascular outcomes. The findings shed light on the prevalence of risk factors for PAD and their association with the disease. These insights can contribute to the development of targeted interventions to reduce adverse clinical outcomes in this population.

Transcriptomics analysis of long non-coding RNAs in smooth muscle cells from patients with peripheral artery disease and diabetes mellitus

Diabetes mellitus (DM) is a significant risk factor for peripheral arterial disease (PAD), and PAD is an independent predictor of cardiovascular disorders (CVDs). Growing evidence suggests that long non-coding RNAs (lncRNAs) significantly contribute to disease development and underlying complications, particularly affecting smooth muscle cells (SMCs). So far, no study has focused on transcriptome analysis of lncRNAs in PAD patients with and without DM. Tissue samples were obtained from our Vascular Biobank. Due to the sample’s heterogeneity, expression analysis of lncRNAs in whole tissue detected only ACTA2-AS1 with a 4.9-fold increase in PAD patients with DM. In contrast, transcriptomics of SMCs revealed 28 lncRNAs significantly differentially expressed between PAD with and without DM (FDR < 0.1). Sixteen lncRNAs were of unknown function, six were described in cancer, one connected with macrophages polarisation, and four were associated with CVDs, mainly with SMC function and phenotypic switch (NEAT1, MIR100HG, HIF1A-AS3, and MRI29B2CHG). The enrichment analysis detected additional lncRNAs H19, CARMN, FTX, and MEG3 linked with DM. Our study revealed several lncRNAs in diabetic PAD patients associated with the physiological function of SMCs. These lncRNAs might serve as potential therapeutic targets to improve the function of SMCs within the diseased tissue and, thus, the clinical outcome.

Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis in Mice.

Restoring the capacity of endothelial progenitor cells (EPCs) to promote angiogenesis is the major therapeutic strategy of diabetic peripheral artery disease. The aim of this study was to investigate the effects of GLP-1 (glucagon-like peptide 1; 32-36)-an end product of GLP-1-on angiogenesis of EPCs and T1DM (type 1 diabetes) mice, as well as its interaction with the classical GLP-1R (GLP-1 receptor) pathway and its effect on mitochondrial metabolism. In in vivo experiments, we conducted streptozocin-induced type 1 diabetic mice as a murine model of unilateral hind limb ischemia to examine the therapeutic potential of GLP-1(32-36) on angiogenesis. We also generated Glp1r-/- mice to detect whether GLP-1R is required for angiogenic function of GLP-1(32-36). In in vitro experiments, EPCs isolated from the mouse bone marrow and human umbilical cord blood samples were used to detect GLP-1(32-36)-mediated angiogenic capability under high glucose treatment. We demonstrated that GLP-1(32-36) did not affect insulin secretion but could significantly rescue angiogenic function and blood perfusion in ischemic limb of streptozocin-induced T1DM mice, a function similar to its parental GLP-1. We also found that GLP-1(32-36) promotes angiogenesis in EPCs exposed to high glucose. Specifically, GLP-1(32-36) has a causal role in improving fragile mitochondrial function and metabolism via the GLP-1R-mediated pathway. We further demonstrated that GLP-1(32-36) rescued diabetic ischemic lower limbs by activating the GLP-1R-dependent eNOS (endothelial NO synthase)/cGMP/PKG (protein kinase G) pathway. Our study provides a novel mechanism with which GLP-1(32-36) acts in modulating metabolic reprogramming toward glycolytic flux in partnership with GLP-1R for improved angiogenesis in high glucose-exposed EPCs and T1DM murine models. We propose that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for peripheral artery disease. URL: www.ebi.ac.uk/metabolights/; Unique identifier: MTBLS9543.

Can acupuncture increase microcirculation in peripheral artery disease and diabetic foot syndrome? - a pilot study.

Globally, diabetes mellitus (DM) and peripheral artery disease (PAD) have an increasing incidence and a high prevalence and are both associated with high morbidity and complication rates, e.g., as chronic non-healing peripheral ulcers. Impaired macro- and microcirculation and peripheral neuropathy lead to an increased risk of foot ulcers and infections. These complications are difficult to treat, have a high risk of becoming chronic and often lead to lower limb amputation. The aim of this planned study was to investigate the potential effects of acupuncture on improving microcirculation in patients with Diabetic Foot Syndrome (DFS) and PAD. In 18 patients with chronic non-healing peripheral ulcers and diagnosed DM or PAD, data on 8 microcirculatory parameters were collected simultaneously on intact skin close to the wound margin. Microcirculation was assessed using an O2C device combining laser Doppler shift and white light spectroscopy (LEA Medizintechnik GmbH, Giessen, Germany). Unilateral and bilateral acupuncture was performed on the connecting line between acupuncture points Stomach 14 and Stomach 15. After unilateral acupuncture (ipsilateral to the wound side), a statistically significant improvement in 7 out of 8 microcirculatory parameters was demonstrated compared to baseline measurements before acupuncture. After bilateral acupuncture, there was an additional improvement and statistical significance in all parameters in both DFS and PAD patients. These results show an improvement in the microcirculation and peripheral blood flow at the edges of the wound. As impaired micro- and macrocirculation is considered to be a critical prognostic factor for the healing of a peripheral lesion, the intervention could have a positive impact on the healing of (chronic) peripheral wounds.

Integrated genetic analysis of diabetic complications: Bioinformatics insights into foot ulcers, neuropathy and peripheral artery disease.

Diabetic foot ulcers (DFU), diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) are common complications of diabetes mellitus, while diabetic peripheral neuropathy and peripheral arterial disease contribute to the pathogenesis of diabetic foot ulcers, and the pathogenic mechanisms between these three diseases still need further investigation. The keywords 'diabetic foot ulcer', 'diabetic peripheral neuropathy' and 'atherosclerosis' were used to search for related gene sets in the GEO database. Differentially expressed genes (DEGs) were screened and analysed for GO, KEGG and enrichR functional enrichment. Potential three disease biomarkers were identified by SVM-SVM-RFE and LASSO regression analysis. The results were also validated using external datasets and discriminability was measured by area under the ROC curve (AUC). Finally, biomarkers and co-upregulated genes were analysed through the GSEA and Attie Laboratories diabetes databases. A total of 11 shared genes (KRT16, CD24, SAMD9L, SRGAP2, FGL2, GPR34, DDIT4, NFE2L3, FBLN5, ANXA3 and CPA3), two biomarkers (SAMD9L and FGL2) and one co-upregulated gene (CD24) were screened. GO and KEGG pathway analysis of DEGs, enrichr enrichment analysis of shared differential genes and GSEA analysis of biomarkers showed that these significant genes were mainly focused on vasoregulatory, inflammatory-oxidative stress and immunomodulatory pathways. In this study, we used bioinformatics to investigate the intrinsic relationship and potential mechanisms of three common lower extremity complications of diabetes and identified two pivotal genes using the LASSO model and the SVM-RFE algorithm, which will further help clinicians to understand the relationship between diabetic complications, improve the diagnosis and treatment of diabetic foot problems and help doctors to identify the potential risk factors of diabetic foot.

Navigating the Complexity: Updates in Diabetes-Related Cardiovascular Complications

The aim of this study is to offer a thorough examination of contemporary research concerning cardiovascular complications induced by diabetes, with a specific focus on coronary artery disease (CAD), diabetic heart attacks, diabetic peripheral artery disease (PAD), and diabetic hypertension. The period of analysis spans from 1988 to 2022, and the data utilized is extracted from secondary sources. Diabetes mellitus is a chronic metabolic disorder associated with an increased risk of cardiovascular complications, including coronary artery disease (CAD), heart attacks, strokes, peripheral artery disease (PAD), and hypertension. These complications are influenced by chronic hyperglycemia, insulin resistance, dyslipidemia, inflammation, and endothelial dysfunction. Diabetic-induced cardiovascular diseases significantly contribute to morbidity and mortality rates worldwide. The studies highlight the potential of plant-derived targeted therapies in reducing inflammation and endothelial dysfunction, providing promising avenues for improving patient outcomes. Additionally, research on diabetes-specific medications, imaging techniques, individualized glycemic targets, and combination therapies reveals new approaches to managing diabetic-induced cardiovascular diseases. Precision medicine, advancements in imaging, and lifestyle interventions offer valuable tools for personalized treatment plans and improved patient care. Public health initiatives that enhance diabetes management, raise awareness, and improve healthcare access are crucial for reducing the burden of cardiovascular complications in Nigeria and other regions affected by diabetes. Further research and collaboration among healthcare professionals will refine our understanding and enhance the management of diabetic-induced cardiovascular diseases, ultimately reducing their impact on individuals with diabetes.

A novel method that can be used in both the diagnosis and treatment of peripheral arterial disease in diabetics: vibration-mediated dilation.

The growing incidence of diabetes and the increasing life expectancy of the diabetic population worldwide has increased the number of diabetic vascular complications occurring in cardiology practice. As current treatment and prevention methods are less effective in this patient group, there is a need for new treatment methods in this area. Exercise, which reduces metabolic and vascular problems associated with diabetes, often becomes impossible, especially in advanced-stage patients who need exercise the most. Since exercise and flow-mediated dilation (FMD) are effective by stimulating mechanotransduction mechanisms on the endothelium, it can be expected that the same mechanisms could also be stimulated by direct vibration. In order to test this hypothesis, in this study, a group of 20 type 2 diabetes patients (11 males, age 56.80 ± 11.05 years and diagnosed for 15.35 ± 8.61 years) were examined via the application of FMD and vibration-mediated dilation (VMD). We performed vibration for five minutes with 20-Hz frequency and 3-mm vertical amplitude, to the same side forearm, with a 30-minute interval. Using a 10-MHz linear echo probe, brachial artery diameter and flow velocities were recorded for 10 minutes before and at two-minute intervals after the FMD and VMD applications. Then brachial artery flow and resistance were calculated at each stage. In the first minute after FMD and VMD applications, brachial artery diameter and flow velocities increased significantly, and vascular resistance decreased significantly. None of the corresponding FMD or VMD parameters in the first minute was different. The artery diameters in the first minute after FMD and VMD were increased by 6.04 ± 5.29 and 5.49 ± 5.21%, respectively. At the tenth minute, these values decreased to 1.73 ± 3.21 and 2.05 ± 3.31%. In the FMD series, all parameters except brachial artery diameter returned to their baseline values after the fourth minute. After VMD, all parameters also decreased after the first minute, but the recovery was much slower. At each stage after the first minute, the VMD averages were higher than the baseline value and their corresponding FMD values. The results of this study indicated that vibration may be a powerful, long-lasting and feasible treatment option in patients with peripheral perfusion failure, developed due to diabetic macro- and microvascular complications.

Unraveling shared risk factors for diabetic foot ulcer: a comprehensive Mendelian randomization analysis

IntroductionDiabetic foot ulcer (DFU) stands as a severe diabetic lower extremity complication, characterized by high amputation rates, mortality, and economic burden. We propose using Mendelian randomization studies to explore shared...

The correlation between transcutaneous oxygen pressure (TcPO2 ) and forward-looking infrared (FLIR) thermography in the evaluation of lower extremity perfusion according to angiosome.

The increased peripheral arterial disease (PAD) incidence associated with aging and increased incidence of cardiovascular conditions underscores the significance of assessing lower limb perfusion. This study aims to report on the correlation and utility of two novel non-invasive instruments: transcutaneous oxygen pressure (TcPO2 ) and forward-looking infrared (FLIR) thermography. A total of 68 patients diagnosed with diabetic foot ulcer and PAD who underwent vascular studies at a single institution between March 2022 and March 2023 were included. Cases with revascularization indications were treated by a cardiologist. Following the procedure, ambient TcPO2 and FLIR thermography were recorded on postoperative days 1, 7, 14, 21 and 28. In impaired limbs, TcPO2 was 12.3 ± 2 mmHg and FLIR thermography was 28.7 ± 0.9°C. TcPO2 (p = 0.002), FLIR thermography (p = 0.015) and ankle-brachial index (p = 0.047) values significantly reduced with greater vascular obstruction severity. Revascularization (n = 39) significantly improved TcPO2 (12.5 ± 1.7 to 19.1 ± 2.2 mmHg, p = 0.011) and FLIR (28.8 ± 1.8 to 32.6 ± 1.6°C; p = 0.018), especially in severe impaired angiosomes. TcPO2 significantly increased immediately post-procedure, then gradually, whereas the FLIR thermography values plateaued from day 1 to 28 post-procedure. In conclusion, FLIR thermography is a viable non-invasive tool for evaluating lower limb perfusion based on angiosomes, comparable with TcPO2 .

Inflammatory Markers Used as Predictors of Subclinical Atherosclerosis in Patients with Diabetic Polyneuropathy.

peripheral arterial disease (PAD) is identified late in diabetic patients because, in the majority of cases, it is associated with diabetic peripheral neuropathy, resulting in little or no symptoms, or symptoms that are completely neglected. In this study were enrolled all patients over 18 years of age, with diabetes mellitus type II for more than a year with poor glycemic control, diagnosed with diabetic polyneuropathy admitted to the Diabetology Department, Emergency County Hospital of Targu Mures, Romania between January 2020 and March 2023. We divided the patients into two groups, based on the presence or absence of subclinical atherosclerosis in the lower limb, named "SA" and "non-SA". Patients in the SA group were older (p = 0.01) and had a higher incidence of IHD (p = 0.03), history of MI (p = 0.02), and diabetic nephropathy (p = 0.01). Moreover, patients with subclinical atherosclerosis had a higher BMI (p < 0.0001) and a longer duration of diabetes (p < 0.0001). Among all patients, the systemic inflammatory markers, MLR (r = 0.331, p < 0.001), NLR (r = 0.517, p < 0.001), PLR (r = 0.296, p < 0.001), SII (r = 0.413, p < 0.001), as well as BMI (r = 0.241, p < 0.001) and HbA1C (r = 0.489, p < 0.001), demonstrated a strong positive correlation with the diabetes duration. The multivariate logistic regression analysis showed that older patients (OR: 2.58, p < 0.001), the male gender (OR: 2.30, p = 0.006), a higher baseline levels of BMI (OR: 7.71, p < 0.001), and the duration of diabetes (OR: 8.65, p < 0.001) are predictors of subclinical atherosclerosis in DN patients. Additionally, the high baseline levels of all systemic inflammatory markers (for all: p < 0.001) and poor diabetes management (OR: 10.4, p < 0.001 for HbA1C; OR: 10.78, p < 0.001 for admission glucose) are independent predictors of SA. the inflammatory markers, NLR, MLR, PLR, and SII, being cheap and easy to collect in routine medical practice from the standard blood tests, could be an important step in predicting vascular outcomes in diabetic patients and the disease's progression, playing a key role in follow-up visits in type-2 diabetic patients and PAD patients.

Assessing the Effects of Pulsed Electromagnetic Therapy on Painful Diabetic Distal Symmetric Peripheral Neuropathy: A Double-Blind Randomized Controlled Trial.

Significant complications of diabetes include pain and the loss of sensation in peripheral limbs. Pain management of diabetic symmetric peripheral neuropathy (DSPN) remains challenging. This study reports on utilizing pulsed electromagnetic field therapy (PEMF) to reduce pain and improve skin perfusion pressure (SPP) in subjects with DSPN. A randomized, sham-controlled, double-blind, clinical trial was conducted on subjects afflicted with foot pain associated with DSPN. Following informed consent, 182 subjects with diabetes and confirmed DSPN were entered into the trial for a period of 18 weeks. Subjects were randomized into active PEMF treatment or nonactive sham and instructed to treat to their feet for 30 minutes, twice daily and report daily pain scores. Some patients in the active arm experienced a transient low field strength notification (LFSN) due to improper pad placement during treatment. Skin perfusion pressure measurements were also collected at two and seven weeks to assess peripheral arterial disease effects via measurement of local microcirculatory flow and blood pressure. Patients in the active arm who did not receive an LFSN experienced a clinically significant 30% reduction in pain from baseline compared to sham (P < .05). Though not statistically significant, SPP in the active group trended toward improvement compared to sham. Pulsed electromagnetic field therapy appears effective as a nonpharmacological means for reduction of pain associated with diabetic peripheral neuropathy and holds promise for improvement of vascular physiology in microcirculatory dysfunction associated with diabetic peripheral arterial disease.

Type 2 cytokines promote angiogenesis in ischemic muscle via endothelial IL-4Rα signaling

Peripheral arterial disease (PAD) is one of the leading causes of cardiovascular morbidity and mortality worldwide, yet current trials on therapeutic angiogenesis remain suboptimal. Type 2 immunity is critical for post-ischemic regeneration, but its regulatory role in revascularization is poorly characterized. Here, we show that type 2 cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), are the key mediators in post-ischemic angiogenesis. IL-4/IL-13-deficient mice exhibit impaired reperfusion and muscle repair in an experimental model of PAD. We find that deletion of IL-4Rα in the endothelial compartment, rather than the myeloid compartment, leads to remarkable impairment in revascularization. Mechanistically, IL-4/IL-13 promote endothelial cell proliferation, migration, and tube formation via IL-4Rα/STAT6 signaling. Furthermore, attenuated IL-4/IL-13 expression is associated with the angiogenesis deficit in the setting of diabetic PAD, while IL-4/IL-13 treatment rescues this defective regeneration. Our findings reveal the therapeutic potential of type 2 cytokines in treating patients with muscle ischemia.

Risk Factors for Ulceration in Diabetes Mellitus in the Preventive Foot Clinic at the Medical Center for Diabetes, Obesity, and Specialties, During the Period January-April 2022.

Introduction: Diabetes Mellitus is a conglomerate of metabolic alterations that chronically affect health. Neuropathy, previous ulcers, foot deformities, peripheral arterial disease, and chronic kidney disease are risk factors that predispose to the development of foot ulcers. It was carried out in order to determine risk factors for ulceration in people living with diabetes mellitus. Materials and methods: Descriptive observational study of 233 people who attended the Preventive Foot consultation at the Diabetes, Obesity and Specialties Medical Center, during the period January-April 2022. Information collected through a questionnaire that reported age, sex, marital status, time of diagnosis of diabetes mellitus, history of ulcer, amputation, bone deformity, chronic renal failure, neuropathy and peripheral arterial disease. Results: 60% female, 40% male, 60% ≥ 62 years. 39.6% with diagnosis time ≥16 years, 65.2%-foot deformity, 12.8% previous ulcer, 5.1% previous amputation, 10.3% chronic renal failure, 36% peripheral neuropathy and 31.3% peripheral arterial disease. 47.6% presented a very low risk, 27.5% moderate, 15% high risk and 9% low. Association time of diagnosis and neuropathy chi2= 8.993, p= &lt;0.029. Ulcer and amputation correlation rho=0.606, p=&lt; .001. Discussion: As risk factors predominated foot deformity, followed by diabetic neuropathy and peripheral arterial disease. With significant association between the time of diagnosis and neuropathy. With moderate direct proportional correlation between ulcer and previous amputation

Republication of “The Evaluation and Treatment of Diabetic Foot Ulcers and Diabetic Foot Infections”

Diabetic foot ulcers and infections are common complications of diabetic foot disease. Additionally, these complications are a common cause of morbidity and impose a substantial burden to the patient and society. It is imperative to understand the major contributing factors, namely, diabetic neuropathy, peripheral arterial disease, and immune system dysfunction in order to guide treatment. Management of diabetic foot disease begins with a detailed history and thorough physical examination. This examination should focus on the manifestations of diabetic neuropathy and peripheral arterial disease, and, in particular, any evidence of diabetic foot ulcers or infection. Prevention strategies should include a multi-disciplinary approach centered on patient education.