Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease

BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.

PREVALENCE AND RISK FACTORS OF PERIPHERAL ARTERIAL DISEASE IN DIABETIC PATIENTS OVER 50 YEARS OLD IN CHINA

Objective To investigate the prevalence of peripheral arterial disease (PAD) in China type 2 diabetic patients and to demonstrate the relationships between putative risk factors and PAD. Methods In total 1 397 type 2 diabetic patients aged 50 years and older were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) in 15 Class III Grade A hospitals in 7 major cities of China. Results Mean patient age was 63.7±8.2 years and mean duration of diabetes mellitus was 9.39±7.4 years. Two hundreds and seventy-two (19.47%) patients were diagnosed as PAD by ABI <0.9, 122 (18.37%) in male and 150 (20.46%) in female. PAD patients had a significantly longer duration of diabetes mellitus, higher hemoglobin Alc, and a significantly lower mean body mass index than non-PAD ones. Aging, smoking, and systolic blood pressure were found to be positively related with the prevalence of PAD. In terms of lipid profiles, no variable was found to relate with PAD. Notably, baPWV showed as the same significant guiding index for PAD, almost matched with ABI. Conclusions PAD is a common complication in China type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for diabetic patients with high risk factors.

Peripheral arterial disease, type 2 diabetes and postprandial lipidaemia: Is there a link?

Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mellitus.Several reasons exist for peripheral arterial disease indiabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally,the use of certain specific postprandial particle markers,such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles.

Relationship of visual impairment and peripheral artery disease with the occurrence of diabetic foot ulcers in Dr. Moewardi Hospital

Objective: One of the diabetes mellitus (DM) complications is foot ulcers. Foot ulcers are influenced by many factors. DM puts patients at risk of injury because of visual impairment. Hyperglycemia can damage blood vessels, which results in peripheral artery disease (PAD). The purpose of this study was to find the relationship of visual impairment and PAD with diabetic foot ulcers. Methods: This research used observational analytic study with case–control methods. It used purposive sampling in 34 DM patients with foot ulcers and 34 DM patients without foot ulcers. The research instruments were an interview guide to assess visual impairment, physical examination to assess PAD, and documentation study, which was used to know the incidence of diabetic ulcers. Results: The results showed that the respondents who experienced ulcers with visual impairment were 44.1% and the respondents who had foot ulcers with PAD were 73.5%. The results of statistical tests showed that there was no relationship between visual impairment and the incidence of ulcers (P = 0.166). The respondents with PAD will have a chance to suffer from foot ulcers 5.808 times higher than those who do not have PAD. Conclusions: There is no relationship between visual impairment and the incidence of diabetic foot ulcers in Dr. Moewardi Hospital, but there is relationship between PAD and the incidence of diabetic foot ulcers in Dr. Moewardi Hospital. Suggestions of this study are to do foot screening and educate about the importance of foot care to prevent the occurrence of diabetic ulcers.

Screening of Peripheral Artery Disease by Systematic Measurement of Ankle-Brachial Index among Diabetic Patients in Dakar

Introduction: The peripheral artery disease (PAD) is one of the chronic and frightening vascular complications of the diabetes whose tracking can be done by the Ankle-Brachial Index (ABI) measurement. We conducted in this context a study which consisted in measuring the ABI among hospitalized diabetic patients at Teaching Hospital of Pikine in Dakar, over 18 months’ duration. The aim was to determine the prevalence and evaluate factors correlated to the presence of the PAD. Patients and Method: This cross-sectional descriptive study interested the whole of diabetic patients hospitalized in Internal Medicine/Endocrinology Department, from January 2013 to June 2014. We carried out a complete clinical examination associated with ABI measurement by a Doppler probe for each included patient after having collected the clinical and paraclinical data. Results: Our population of study comprised 209 diabetic patients with a female predominance (126, 60.3%). The sex-ratio man/woman was 0.6. The median age of the population of study was 54 ± 2 years. In our series, 157 (75.1%) patients discovered their diabetes with the waning of an affection while the 52 (24.9%) other patients discovered their diabetes at the time of a systematic assessment. The PAD appeared by an intermittent claudication among 38 patients (18.2%). The ABI was normal for 126 patients (60.3%). The ABI was low for 51 patients (24.4%), unilateral in 3.8% of cases and bilateral in 20.6% of cases. The ABI was high among 32 patients (15.3%), unilateral in 7.2% of cases and bilateral in 8.1% of cases. The ABI extremes values were 0.11 and 2. In the population of study, 46 patients (22%) had a well-compensated PAD. The PAD was low compensated for 3 patients (1.4%) and severe for 2 patients (1%). The ABI was more frequent and significantly among women than men, with 32 cases (25.4%) against 19 (22.9%) cases (p = 0.021). The proportion of low ABI was more important among patients whose diabetes had evolved for more than 5 years (42.3% of cases) with a peak of frequency in the duration of 6 - 10 years (47.7% of cases). Conclusion: The PAD global prevalence among hospitalized diabetic patients appeared high with 24.4% patients presenting low ABI. Its early diagnosis among subjects at risk as for our study population allowed identifying asymptomatic subjects having another cardiovascular damage. Thus, the screening of obstructive arteriopathy of lower limb PAD by the measurement of ABI should be applied to all diabetic patients for a better assessment of atherosclerotic complication.

Transplantation of mobilized peripheral blood mononuclear cells for peripheral arterial occlusive disease of the lower extremity

Objectives To assess the clinical efficacy,safety,and feasibility of autologous transplantation of mobilized peripheral blood mononuclear cells(PBMNCs)for patients with peripheral arterial occlusive disease(PAOD)of the lower extremity.Methods A total of 152 patients with PAOD of the lower extremity were enrolled into this non-controlled observational study from November 2003 to March 2006.All patients received subcutaneous injections of recombinant human granulocyte colony-stimulating factor(G-CSF,450-600μg/day)for 5 days in order to mobilize stem/progenitor cells;their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs.Patients were followed up for at least 12 weeks.Results At 12 weeks,primary manifestations,including lower limb pain and coldness,were significantly improved in 137(90.1%)of the patients;limb ulcers improved or healed in 46(86.8%)of the 53 patients,while 25 of the 48(47.9%)patients with limb gangrene remained steady or improved.Ankle-brachial index(ABI)improved in 33(22%)of the cases,and TcPO_(2) increased in 45(30%)of the cases.Angiography before treatment,and at 12 weeks after treatment,was performed in 10 of the patients and showed formation of new collateral vessels.No severe adverse effects or complications specifically related to cell transplantation were observed.Conclusion Autologous transplantation of G-CSF-mobilized PBMNCs might be a safe and effective treatment for lower limb ischemic disorder.

Accuracy of Doppler Ultrasonography in Assessment of Lower Extremity Peripheral Arterial Diseases

Doppler ultrasound scan is a non-invasive, cheap and convenient tool and it complements angiography, Computed tomography angiography (CTA), magnetic resonance angiography (MRA) and catheter digital subtraction angiography (DSA) in screening, diagnosis, treatment and follow-up of peripheral vascular diseases. Symptoms of peripheral vascular diseases are becoming more common due to rise in incidence of diseases and risk factors (diabetes mellitus, dyslipidemias, smoking, sedentary lifestyle). Due to limited availability of highly specific tools such as CT angiography, magnetic resonance angiography (MRA) and DSA (digital subtraction angiography) in many developing countries, doppler ultrasound is gaining more importance. Early determination of peripheral arterial diseases is beneficial in prevention of complications as severity increases may cause intermittent claudication, pain, tissue loss, including ulceration and gangrene (as the diseases progresses) and early management of arteriosclerosis will be beneficial to prevent these complications.

Clinical analysis of 35 cases of peripheral arterial disease

Objective To analyse the current condition in diagnosis and treatment of peripheral arterial disease (PAD). Methods:35 cases of PAD hospitalized between July 2007 and May 2008 were collected and studied.Results:14 of them had the concomitant type 2,diabetes mellitus (shortly as DM) and 18 cases with ulcers or gangrene in the lower limb,up to 14 were found with DM.5 died of pulmonary infection and 1 died of multiple system organ failure (MSOF).Conclu- sion:DM was an important risk factor of PAD.PAD tended to start in younger age in those with DM and its local lesion was frequently more severe and often less effective in revasculation treatment.Death during hospitalization was mainly due to related complications from cerebral vascular problems but not DM.

Peripheral artery disease in patients with diabetes:Epidemiology,mechanisms,and outcomes

Peripheral artery disease(PAD) is the atherosclerosis of lower extremity arteries and is also associated with atherothrombosis of other vascular beds,including the cardiovascular and cerebrovascular systems.The presence of diabetes mellitus greatly increases therisk of PAD,as well as accelerates its course,making these patients more susceptible to ischemic events and impaired functional status compared to patients without diabetes.To minimize these cardiovascular risks it is critical to understand the pathophysiology of atherosclerosis in diabetic patients.This,in turn,can offer insights into the therapeutic avenues available for these patients.This article provides an overview of the epidemiology of PAD in diabetic patients,followed by an analysis of the mechanisms by which altered metabolism in diabetes promotes atherosclerosis and plaque instability.Outcomes of PAD in diabetic patients are also discussed,with a focus on diabetic ulcers and critical limb ischemia.

Diabetes and peripheral artery disease:A review

Peripheral arterial disease(PAD)refers to partial or complete occlusion of the peripheral vessels of the upper and lower limbs.It usually occurs as part of systemic atherosclerosis in the coronary and cerebral arteries.The prevalence of PAD is expected to continue to increase in the foreseeable future owing to the rise in the occurrence of its major risk factors.Nonhealing ulcers,limb amputation and physical disability are some of its major complications.Diabetes mellitus(DM)remains a major risk for PAD,with DM patients having more than two-fold increased prevalence of PAD compared with the general population.The clinical presentation in people with DM also differs slightly from that in the general population.In addition,PAD in DM may lead to diabetic foot ulcers(DFUs),which precipitate hyperglycaemic emergencies and result in increased hospital admissions,reduced quality of life,and mortality.Despite the epidemiological and clinical importance of PAD,it remains largely under diagnosed and hence undertreated,possibly because it is largely asymptomatic.Emphasis has been placed on neuropathy as a cause of DFUs,however PAD is equally important.This review examines the epidemiology,pathophysiology and diagnosis of lower limb PAD in people with diabetes and relates these to the general population.It also highlights recent innovations in the management of PAD.

Control of modifiable risk factors and major adverse cardiovascular events in people with peripheral artery disease and diabetes

BACKGROUND People with diabetes and peripheral artery disease(PAD)have a high risk of major adverse cardiovascular events(MACE).Prior research suggests that medical therapies aimed to control modifiable risk factors are poorly implemented in patients with PAD.AIM To examine the association between the control of modifiable risk factors,estimated by the novel PAD-medical score,and the incidence of MACE in people with PAD and diabetes.METHODS Participants were recruited from out-patient clinics if they had a diagnosis of both PAD and diabetes.Control of reversible risk factors was assessed by a new composite measure,the PAD-medical score.This score takes into account the control of low-density lipoprotein cholesterol,blood pressure,blood glucose,smoking and prescription of an anti-platelet.Participants were followed to record incidence of myocardial infarction,stroke and cardiovascular death(MACE).The association of PAD-medical score with MACE was assessed using Cox proportional hazard analyses adjusting for age,sex and prior history of ischemic heart disease and stroke.RESULTS Between 2002 and 2020,a total of 424 participants with carotid artery disease(n=63),aortic or peripheral aneurysm(n=121)or lower limb ischemia(n=240)were prospectively recruited,and followed for a median duration(inter-quartile range)of 2.0(0.2–4.4)years.Only 33(7.8%)participants had the optimal PAD-medical score of five,with 318(75%)scoring at least three out of five.There were 89(21.0%)participants that had at least one MACE during the follow-up period.A one-unit higher PAD-medical score was associated with lower risk of MACE(HR=0.79,95%CI:0.63-0.98)after adjusting for other risk factors.CONCLUSION The PAD-medical score provides a simple way to assess the control of modifiable risk factors targeted by medical management aimed to reduce the incidence of MACE.

Macroangiopathic Complications and Associated Factors in Type 2 Diabetics at CNHU-HKM

Nowadays, chronic clinical manifestations of diabetemellitus constitute an important disease and a huge public health issue. Aim: Study the macroangiopathic complications in type 2 diabetics. Method: It is a descriptive cross-sectional study with an analytical aim covering the period from January 2019 to December 31, 2021 in the Endocrinology, Metabolism and Nutrition clinic of the National Teaching Hospital Hubert Koutoukou Maga (CNHU-HKM) We thus identified 150 type 2 diabetic patients. Results: The prevalence of macroangiopathy was 60% with 11.3% for stroke, 28.6% for acute coronary syndrom, 4% for cervical macroangiopathy, and 46.97% ± 25.36% for obliterating arteriopathy of the lower limbs (OALL). The mean age of the patients was 57.69 ± 1.77 years with a sex ratio 1. The duration of diabetes progression was greater than 10 years for more than half of the patients 52.6%. The main associated cardiovascular risk factors were arterial high blood pressure (64.7%), family history of diabetes (33.7%), obesity with 20.0%. The death rate was 7.3%. Conclusion: Macroangiopathy’s mortality rate of in type 2 diabetics is high. Prevention remains the best treatment and involves screening for factors associated with macroangiopathy.

Percutaneous Angioplasty in Diabetic Patients with Critical Limb Ischemia and Chronic Kidney Disease

Introduction: Diabetes and Chronic Kidney Disease (CKD) are two strong risk factors for peripheral arterial disease (PAD) and Critical Limb Ischemia (CLI). Further renal insufficiency increases the risk of non healing wounds and major amputation. Primary amputation rates of 22% to 44% have been reported for ischaemic foot lesion in End-Stage Renal Disease (ESRD) patients. In our study we evaluated the outcomes after Percutaneus Transluminal Angioplasty (PTA) in diabetic patient in relation to different CKD classes. Materials and Methods: We studied a group of 456 diabetic patients with PAD complicated by foot lesion who underwent PTA because of a CLI. According to the estimated Glomerular Filtration Rate (eGFR mL/min/1.73 m2) we divided the patients into five CKD groups: group 1 eGFR > 90, group 2 eGFR 90 - 60 (n = 160), group 3 eGFR 60 - 30 (n = 152), group 4 eGFR 30 -15 (n = 34) and group 5 < 15 or in ESRD) (n = 60). The following outcomes were recorded: alive without major amputation, alive with major amputation and death. The follow-up was 16.7 ± 14.3 months. Results: Alive without major amputation, alive with major amputation and death were respectively: for group 1 (77.8%, 11.1%, 11.1%), for group 2 (74.4%, 12.5%, 13.1%), for group 3 (80.3%, 11.2%, 8.5%), for group 4 (82.3%, 8.8%, 8.8%). They were 60%, 18.3%, 21.7% for group 5 significantly different from the other CKD groups (χ2 = 0.0175). Our analysis did not highlight any relationship between eGFR and outcomes and eGFR did not show any significant difference according to the different outcomes, and were respectively 60.2 ± 1.3, 61.8 ± 3.4, 63.8 ± 3.5 (P = ns). Conclusion: The outcomes were similar for groups 1-4 and therefore, according to our data, they seemed not to be influenced by the decline of GFR. Outcomes worse significantly in group 5, but this group included only patients with ESRD in dialysis treatment. Although the outcomes after PTA in group 5 was significantly worse than the other groups, still a 60% limb salvage rate was obtained with PTA also in these very fragile patients. PTA was much less aggressive than by-pass and PTA was the only method used to treat CLI in our patients. This could explain why we recorded similar outcomes in all groups despite the decline of GFR that, generally speaking, mirrors a worsening of the general clinical conditions. Worse outcomes were recorded only in group 5 and in this group dialysis by itself might be responsible of the different outcomes.

Prevalence and related risk factors of peripheral arterial disease in elderly patients with type 2 diabetes in Wuhan, Central China

Background The investigations of prevalence and risk factors of peripheral arterial disease （PAD） in type 2 diabetic patients have been carried out in many countries and regions, except for Central China. In this study, we determined the prevalence of PAD in type 2 diabetic patients and the related factors that gave rise to increasing of the risk of PAD development in Wuhan, China. Methods The study enrolled 2010 patients aged 60 years and older who were regularly visiting the Central Hospital of Wuhan that is a public hospital from 2005 to 2010, where all residents of the city were offered the medical services. PAD was defined as an ankle-brachial index 〈0.90 in either leg. To evaluate the role of various risk factors in PAD development, uniformed interviews, clinical examinations and laboratory investigation of all of participants were performed in this study. The correlation between potential risk factors and PAD was analyzed. Results In Wuhan, the prevalence rate of PAD was 24.1% in elderly diabetic patients. Totally, 291 patients with PAD had at least one weak but not absent dorsalis pedis pulse in both feet, while 541 patients without PAD showed this way. At least one absent dorsalis pedis pulse was found in 192 patients with PAD as well as 10 patients without PAD. The results of multivariate regression analysis suggested that the age, smoking history, hypertension, diabetic neuropathy and macroangiopathy gave rise to significant increase of PAD development in type 2 diabetic diseases. Conclusions The prevalence of PAD in elderly patients with type 2 diabetes in Wuhan was close to the prevalence that was reported in other regions of China and other Asian countries. Control of the related risk factors and early diagnosis of PAD may play a role in PAD prevention and improving prognosis.

Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

Objective： Type 2 diabetes coexistent with lower extremity artery disease （peripheral arterial disease （PAD）） can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis-the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor （vascular endothelial growth factor A （VEGF-A）） and angiogenesis inhibitors （soluble VEGF receptors type 1 and type 2 （sVEGFR-1 and sVEGFR-2）） in patients with PAD. Methods： Among 46 patients with PAD under pharmacological therapy （non-invasive）, we identified, based on medical history, a subgroup with coexistent type 2 diabetes （PAD-DM2＋, n=15） and without diabetes （PAD-DM2-, n=31）. The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay （ELISA） method. Results： The subgroups of PAD-DM2＋ and PAD-DM2- revealed significantly higher concentrations of VEGF-A （P=-0.000007 and P=0.0000001, respectively） and significantly lower sVEGFR-2 levels （P=-0.02 and P=-0.00001, respectively）, when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients. Conclusions： The coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor （VEGF-A） and higher levels of anglogenesis inhibitors （sVEGFR-1 and sVEGFR-2） at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs.

Diabetic foot ulcer: Challenges and future

Diabetic foot ulcers(DFUs)have become one of the important causes of mortality and morbidity in patients with diabetes,and they are also a common cause of hospitalization,which places a heavy burden on patients and society.The prevention and treatment of DFUs requires multidisciplinary management.By controlling various risk factors,such as blood glucose levels,blood pressure,lipid levels and smoking cessation,local management of DFUs should be strengthened,such as debridement,dressing,revascularization,stem cell decompression and oxygen therapy.If necessary,systemic anti-infection treatment should be administered.We reviewed the progress in the clinical practice of treating DFUs in recent years,such as revascularization,wound repair,offloading,stem cell transplantation,and anti-infection treatment.We also summarized and prospectively analyzed some new technologies and measurements used in the treatment of DFUs and noted the future challenges and directions for the development of DFU treatments.

Patient selection and preparation strategies for the use of contrast material in patients with chronic kidney disease

The prevalence of chronic kidney disease and peripheral arterial disease is increasing.Thus,it is increasingly problematic to image these patients as the number of patients needing a vascular examination is increasing accordingly.In high-risk patients with impaired kidney function,intravascular administration of iodinated contrast media can result in contrast-induced acute kidney injury and Gadolinium can induce nephrogenic systemic fibrosis(NSF).It is important to identify these highrisk patients by means of se-creatinine/e glomerular filtration rate.The indication for contrast examination should counterbalance the increased risk.One or more alternative examination methods without contrast media,such as CO 2 angiography,Ultrasound/Doppler examination or magnetic resonance angiography without contrast should be considered,but at the same time,allow for a meaningful outcome of the examination.If contrast is deemed essential,the patient should be well hydrated,the amount of contrast should be restricted,the examination should be focused,metformin and diuretics stopped,and renal function monitored.Sodium bicarbonate and N-acetylcysteine are popular but their efficiency is not evidence-based.There is no evidence that dialysis protects patients with impaired renal function from contrast-induced nephropathy or NSF.

Diabetic foot ulcers: A devastating complication of diabetes mellitus continues non-stop in spite of new medical treatment modalities

Diabetic foot ulcer is a devastating complication of diabetes mellitus and significant cause of mortality and morbidity all over the world and can be complex and costly.The development of foot ulcer in a diabetic patient has been estimated to be 19%-34%through their lifetime.The pathophysiology of diabetic foot ulcer consist of neuropathy,trauma and,in many patients,additional peripheral arterial disease.In particular,diabetic neuropathy leads to foot deformity,callus formation,and insensitivity to trauma or pressure.The standard algorithms in diabetic foot ulcer management include assessing the ulcer grade classification,surgical debridement,dressing to facilitate wound healing,offloading,vascular assessment(status and presence of a chance for interventional vascular correction),and infection and glycemic control.Although especially surgical procedures are sometimes inevitable,they are poor predictive factors for the prognosis of diabetic foot ulcer.Different novel treatment modalities such as nonsurgical debridement agents,oxygen therapies,and negative pressure wound therapy,topical drugs,cellular bioproducts,human growth factors,energy-based therapies,and systematic therapies have been available for patients with diabetic foot ulcer.However,it is uncertain whether they are effective in terms of promoting wound healing related with a limited number of randomized controlled trials.This review aims at evaluating diabetic foot ulcer with regard to all aspects.We will also focus on conventional and novel adjunctive therapy in diabetic foot management.

Overcoming ischemia in the diabetic foot:Minimally invasive treatment options

As the global burden of diabetes is rapidly increasing,the incidence of diabetic foot ulcers is continuously increasing as the mean age of the world population increases and the obesity epidemic advances.A significant percentage of diabetic foot ulcers are caused by mixed micro and macro-vascular dysfunction leading to impaired perfusion of foot tissue.Left untreated,chronic limb-threatening ischemia has a poor prognosis and is correlated with limb loss and increased mortality;prompt treatment is required.In this review,the diagnostic challenges in diabetic foot disease are discussed and available data on minimally invasive treatment options such as endovascular revascularization,stem cells,and gene therapy are examined.

Understanding the multifaceted etiopathogenesis of foot complications in individuals with diabetes

Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of insulin.Diabetic foot disease,which comprises the spectrum of infection,ulceration,and gangrene,is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic patients.The aim of this study is to provide an evidence-based overview of diabetic foot complications.Due to neuropathy,diabetic foot infections can occur in the form of ulcers and minor skin lesions.In patients with diabetic foot ulcers,ischemia and infection are the main causes of non-healing ulcers and amputations.Hyperglycemia compromises the immune system of individuals with diabetes,leading to persistent inflammation and delayed wound healing.In addition,the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial resistance.As a further complicating factor,the warning signs and symptoms of diabetic foot problems can easily be overlooked.Issues associated with diabetic foot complications include peripheral arterial disease and osteomyelitis;accordingly,the risk of these complications in people with diabetes should be assessed annually.Although antimicrobial agents represent the mainstay of treatment for diabetic foot infections,if peripheral arterial disease is present,revascularization should be considered to prevent limb amputation.A multidisciplinary approach to the prevention,diagnosis,and treatment of diabetic patients,including those with foot ulcers,is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.