Ischemia In Diabetic Patients Research Articles

Mild hypothermia alleviates diabetes aggravated cerebral ischemic injury via activating autophagy and inhibiting pyroptosis

Diabetic patients manifest with more severe neurological deficits than non-diabetes after ischemic stroke. It has been shown that hypothermia has neuroprotective effects on cerebral ischemia, but whether it is effective for cerebral ischemia in diabetic patients remains unknown. The aim of this study was to investigate whether hypothermia can alleviate cerebral ischemic injury in diabetic rats and the regulation of autophagy and pyroptosis of the treatment. We introduced permanent middle cerebral artery occlusion (pMCAO) in a model of type 2 diabetic rats prepared by high-fat diet combined with intraperitoneal injection of STZ in vivo and mimicked cerebral ischemia with diabetes by employing high glucose stimulation and oxygen–glucose deprivation/reoxygenation (OGD/R) in vitro. Moreover, 3-methyladenine and bafilomycin A1 were used to evaluate the association between autophagy and pyroptosis in vitro. Our results showed that diabetes aggravated neurological deficits, increased the volume of cerebral infarction and brain edema as well as the blood brain barrier permeability after cerebral ischemia, which were alleviated by mild hypothermia. Compared with the pMCAO model in non-diabetic rats and OGD/R model without high glucose stimulation in vitro, the expression of P62, NOD-like receptor protein 3 (NLRP3), cleaved caspase-1 and Gasdermin-N increased and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ decreased in the pMCAO model in diabetic rats and OGD/R model with high glucose stimulation, which could be reversed by mild hypothermia. In conclusion, mild hypothermia alleviated diabetes aggravated cerebral ischemic injury via activating autophagy and inhibiting pyroptosis.

Quantitative analysis of retinal and choroid capillary ischaemia using optical coherence tomography angiography in type 2 diabetes.

To perform a quantitative analysis of retinal and choroid capillary ischaemia in diabetic patients by using optical coherence tomography angiography (OCTA). A total of 97 type 2 diabetic patients and 48 controls were included in this cross-sectional study. Diabetic patients without diabetic retinopathy (DR) were categorized as no DR (NDR) group; DR was classified into mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR and proliferative diabetic retinopathy (PDR). Quantitative parameters included foveal and parafoveal vascular density (VD) in superficial, deep and choroid capillary plexus (SCP, DCP and CCP), and foveal flow area in CCP. Stepwise comparisons between groups were performed in the adjacent stages. Diabetic patients had significantly lower flow area in CCP and VD in all three layers compared with controls. In NDR group, foveal flow area in CCP significantly decreased compared with controls. In mild NPDR, parafoveal VD significantly decreased in all three layers compared with NDR, especially in temporal and nasal areas. In moderate NPDR, VD reduction extended to the inferior area in SCP and DCP compared with mild NPDR. In severe NPDR, progressive losses of VD were presented in all layers compared with moderate NDPR. In PDR, the superior VD in SCP significantly increased compared with severe NPDR. In diabetic patients, the microvascular ischaemia originated in choroid layer and extended inward affecting the deep and superficial layer. OCTA can serve as a reliable method for early detection and to monitor progressions in diabetic retinopathy.

Association of carotid intima-media thickness with exercise tolerance test in type 2 diabetic patients

AimsAtherosclerosis and ischemic heart disease are more common in diabetic patients. Atherosclerosis process can disturb the normal functioning of the vascular endothelium and increase vessel wall thickness. The aim of this study was the comparison of Carotid intima-media thickness (CIMT) with Exercise tolerance test as an alternative way to evaluate cardiac ischemia in diabetic patients. MethodsIn a cross-sectional study, 30 diabetic patients with positive exercise test and 30 diabetic patients with negative exercise test were enrolled. CIMT of the carotid artery in both groups of patients was measured. ResultCIMT in the patients with positive and negative exercise test were 1.04 ± 0.21 mm and 0.61 ± 0.11 mm, respectively (P < 0.001). CIMT in positive exercise test group was positively associated with age and negatively associated with gender, FBS, HDL and LDL cholesterol and in negative exercise group was negatively associated with gender, age, FBS, HDL and LDL cholesterol. ConclusionConsidering observed significant positive association between CIMT with result of exercise tolerance test (ETT) in type 2 diabetic patients, it may possible to use CIMT as an inexpensive and non-invasive method for evaluation of ischemic heart disease in diabetic patients.

Peripheral Blood Mononuclear Cells Therapy for Treatment of Lower Limb Ischemia in Diabetic Patients: A Single-Center Experience

The aim of this study is to analyze the effects of peripheral blood mononuclear cells (PBMNCs) therapy in diabetic patients with critical limb ischemia (CLI), with particular regard to its application, as adjuvant therapy in patients underwent endovascular revascularization. Fifty diabetic patients affected by CLI were enrolled. All patients underwent PBMNCs therapy. Thirty-two patients underwent PBMNCs therapy associated with endovascular revascularization (adjuvant therapy group). In 18 patients, who were considered nonrevascularizable or underwent unsuccessful revascularization, regenerative therapy with PBMNCs was performed as the therapeutic choice (PBMNCs therapy group). The median follow-up period was 10months. The baseline and end point results in adjuvant group were as follows. The mean transcutaneous partial pressure of oxygen (TcPO2) improved from 25±9.2mmHg to 45.6±19.1mmHg (P<0.001), and visual analogue scale (VAS) score means decreased from 8.6±2.1 to 3.8±3.5 (P=0.001). In PBMNCs therapy group, the mean TcPO2 improved from 16.2±7.2mmHg to 23.5±8.4mmHg (P<0.001), and VAS score means decreased from 9±1.1 to 4.1±3.3 (P=0.001). Major amputation was observed in 3 cases (9.4%), both in adjuvant therapy group and in PBMNCs therapy one (16.7%) (P=0.6). The role of cellular therapy with PBMNCs is decisive in the patients that are not susceptible to revascularization. In diabetic patients with CLI and healing resistant ulcers, the adjuvant PBMNCs therapy could represent a valid therapeutic option.

Effect of Diallyl Trisulfide on Ischemic Tissue Injury and Revascularization in a Diabetic Mouse Model.

Background and Objective:Allitridin [diallyl trisulfide (DATS)] is an extract from garlic (Allium sativum) that putatively improves endothelial function and is protective against cardiovascular diseases. Endothelial dysfunction after tissue ischemia in diabetic patients is partially due to poor angiogenic response. This study investigated whether DATS may improve angiogenesis in a diabetic mouse model with hind limb ischemia.Methods:Streptozotocin was administered by intraperitoneal injection to establish the model of diabetes in male C57BL/6 mice. After 14 days, nondiabetic and diabetic mice (n = 24, each) underwent unilateral hind limb ischemia by femoral artery ligation. The mice were apportioned to 4 groups: nondiabetic treated (or not) with DATS and diabetic treated (or not) with DATS. DATS treatment consisted of a single daily intraperitoneal injection of 500 μg·kg−1·d−1 for 14 days, beginning on the day of induced ischemia. Ischemia was scored by standard criteria. Blood perfusion was determined using thermal infrared imaging. Tissue capillary density and oxidative stress levels were measured by immunohistochemistry and immunofluorescence, respectively. Serum lipids were measured by enzymatic colorimetric assay. Fasting serum insulin was detected using an insulin enzyme-linked immunosorbent assay kit. Nitric oxide (NO) metabolites and protein carbonyls in tissues were determined by enzyme-linked immunosorbent assay. Targeted protein concentrations were measured by western blotting.Results:At 14 days after ligation, the ischemic skeletal muscle of the streptozotocin-induced diabetic mice had lower levels of endothelial NO synthase, phosphorylated endothelial NO synthase, and vascular endothelial growth factor compared with nondiabetic group. In addition, the hind limb blood perfusion, capillary density, and NO bioactivity were lower in the diabetic group, whereas oxidative stress and protein carbonyl levels were higher. These changes were ameliorated by DATS treatment.Conclusions:DATS treatment of diabetic mice promoted revascularization in ischemic tissue.

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels.

Diabetes mellitus is one the strongest risk factors for cardiovascular disease and, in particular, for ischemic heart disease (IHD). The pathophysiology of myocardial ischemia in diabetic patients is complex and not fully understood: some diabetic patients have mainly coronary stenosis obstructing blood flow to the myocardium; others present with coronary microvascular disease with an absence of plaques in the epicardial vessels. Ion channels acting in the cross-talk between the myocardial energy state and coronary blood flow may play a role in the pathophysiology of IHD in diabetic patients. In particular, some genetic variants for ATP-dependent potassium channels seem to be involved in the determinism of IHD.

Abstract 141: Systolic Blood Pressure and White Matter Hyperintensity Progression in ACCORD-MIND

Introduction: Small vessel disease can be detected on MRI as white matter hyperintensity (WMH), but its pathophysiology remains elusive. We sought to examine the effect of elevated systolic blood pressure (SBP) and SBP variability on WMH progression in the ACCORD-MIND study of patients with type II diabetes, a prototypical small vessel disease. Methods: MRIs were acquired at baseline and 40 months after enrollment. WMH volume (WMHv) was segmented using an automated volumetric algorithm. The primary outcome was ΔWMHv in mm 3 , between the two MRI time points. SBP variability was represented as standard deviation and coefficient of variation. Linear regression models were fitted to ΔWMHv with 10 unit shifts in SBP mean and variability as the primary predictors. Results: After excluding one patient for missing data, 502 patients had, on average, 17 (SD±7) SBP readings. In linear regression, SBP variability was not associated with ΔWMHv, while SBP mean was positively associated with ΔWMHv (Table 1). Furthermore, there was an increase in mean ΔWMHv per quartile of mean SBP (Figure 1). The same analysis was performed for diastolic blood pressure and mean arterial pressure, without significant findings. Conclusions: In this uniform cohort of patients with type II diabetes, higher SBP mean, but not SBP variability, was associated with WMHv progression. For every 10 mm Hg increase in SBP mean during ACCORD-MIND, there was a 1.4 mm 3 increase in ΔWMHv. These data reinforce the role of hypertension in the pathophysiology of cerebral small vessel disease and provide additional rationale for SBP control to prevent chronic microvascular ischemia in diabetic patients.

Surgical Revascularization in Chronic Limb-threatening Ischemia in Diabetic Patients.

Introduction: Diabetes mellitus is one of the chronic diseases that showed a steady increase in the number of patients in the last decades. After the diagnosis of diabetes mellitus, evolution towards limb amputation goes, step by step, through neuropathy, leg ulcers and infection appearance. The existence of diabetic arteriopathy prevents ulcer's healing due to the limb's ischemic status. By restoring arterial flow in the lower extremity, we solve the most important cause for diabetic foot ulcers, namely ischemia. Material and Methods: In the Surgery Clinic of Dr I Cantacuzino Clinical Hospital, Surgical Repair of Diabetic Foot Compartment, the first revascularizations were made approx 5 years ago. During this time we have made constant efforts to lower the number of major amputations by diversifying the interventions dedicated almost exclusively to patients with ulcer of the diabetic foot. Results: The number of major amputations is lower after revascularisation and we have obtained complete ulcer's healing and a functional extremity. We have 80 patients in observation who underwent revasculariosation surgery, ages between 40 and 75 years, 46 men and 34 women. All of them were diabetic patients with critical ischemia and various associated comorbidities: 24% arterial hypertension, 14% polineuropathy, 12% dyslipidemia. The complications occured in the first year of follow-up were 14 cases of graft thrombosis and only 6 cases of major amputation. Conclusions: Before tempting any type of amputation, major or minor, after local infection control by treatment, debridement or dressings, and after vascular evaluation, it is essential to restore arterial flow.

Cell therapy of critical limb ischemia in diabetic patients - State of art.

In this review we report on the state of cell therapy of critical limb ischemia (CLI) with respect to differences between diabetic and non-diabetic patients mainly from the clinical point of view. CLI is the most severe form of peripheral arterial disease and its diagnosis and treatment in diabetic patients is very difficult. The therapeutic effect of standard methods of CLI treatment is only partial - more than one third of diabetic patients are not eligible for standard revascularization; therefore, new therapeutic techniques such as cell therapy have been studied in clinical trials. Presence of CLI in patients with diabetic foot disease is associated with worse clinical outcomes such as lack of healing of foot ulcers, major amputations and premature mortality. A revascularization procedure cannot be successful as the only method in contrast to patients without diabetes, but it must always be part of a complex therapy focused not only on ischemia, but also on treatment of infection, off-loading, metabolic control of diabetes and nutrition, local therapy, etc. Therefore, the main criteria for cell therapy may vary in diabetic patients and non-diabetic persons and results of this treatment method should always be assessed in the context of ensuring comprehensive therapy. This review carries out an analysis of the source of precursor cells, route of administration and brings a brief report of published data with respect to diabetic and non-diabetic patients and our experience with autologous cell therapy of diabetic patients with CLI. Analysis of the studies in terms of diabetes is difficult, because in most of them sub-analysis for diabetic patients is not performed separately. The other problem is that it is not clear if diabetic patients received adequate complex treatment for their foot ulcers which can strongly affect the rate of major amputation as an outcome of CLI treatment.

Role of plasma growth factor in the healing of chronic ulcers of the lower legs and foot due to ischaemia in diabetic patients.

IntroductionIt has been demonstrated that plasma growth factor (PGF) responsible for proliferation of smooth muscle cells and fibroblasts significantly shortens treatment duration.AimTo determine the role of human growth factor in the healing of ulcers due to ischaemic diabetic foot syndrome (DFS) following previous angioplasty of the blood vessels of the lower leg and foot.Material and methodsThe study group included 50 patients with ischaemic diabetic foot complicated by lower leg ulcers in which angioplasty of the stenotic arteries in the distal lower leg and foot was performed. It has been assumed that the area of the ulcer cannot exceed 5 cm2. Following surgical debridement, each patient received platelet-rich plasma in the form of dressings applied on an ulcer, followed by hydrocolloid dressings. Each dressing was replaced after 10 days, and this procedure was repeated after 20 and 30 days of treatment. The control group included 50 patients with ischaemic diabetic foot complicated by an ulcer up to 5 cm2. Angioplasty of the lower leg arteries was also performed in this group. However, after surgical debridement, wounds were covered with hydrocolloid dressings.ResultsAfter 3 months of combined treatment, all wounds in the study group healed whereas in the control group, only wounds of the smallest size healed.ConclusionsCombined treatment of ulcers due to ischaemic DFS with endovascular procedures to re-establish blood flow to the vessels and dressings with autologous platelet-rich plasma significantly shortens the healing time.

The emerging role of microdialysis in diabetic patients undergoing amputation for limb ischemia.

Lower limb ischemia in diabetic patients is a result of macro- and microcirculation dysfunction. Diabetic patients undergoing limb amputation carry high mortality and morbidity rates, and decision making concerning the level of amputation is critical. Aim of this study is to evaluate a novel microdialysis technique to monitor tissue microcirculation preoperatively and predict the success of limb amputation in such patients. Overall, 165 patients with type 2 diabetes mellitus undergoing lower limb amputation were enrolled. A microdialysis catheter was placed preoperatively at the level of the intended flap for the stump reconstruction, and the levels of glucose, glycerol, lactate and pyruvate were measured for 24consecutive hours. Patients were then amputated and monitored for 30 days regarding the outcome of amputation. Failure of amputation was defined as delayed healing or stump ischemia. Patients were divided into two groups based on the success of amputation. There was no difference between the two groups regarding gender, ASA score, body mass index, comorbidities, diagnostic modality used, level of amputation, as well as glucose, glycerol, and pyruvate levels. However, local concentrations of lactate were significantly different between the two groups and lactate/pyruvate (L/P) ratio was independently associated with failed amputation (threshold defined at 25.35). Elevated preoperative tissue L/P ratio is independently associated with worse outcomes in diabetic patients undergoing limb amputation. Therefore, preoperative tissue L/P ratio could be used as a predicting tool for limb amputation's outcome, although more clinical data are needed to provide safer conclusions.

Restoration of Hydrogen Sulfide Production in Diabetic Mice Improves Reparative Function of Bone Marrow Cells.

Bone marrow cell (BMC)-based treatment for critical limb ischemia in diabetic patients yielded a modest therapeutic effect resulting from cell dysfunction. Therefore, approaches that improve diabetic stem/progenitor cell functions may provide therapeutic benefits. Here, we tested the hypothesis that restoration of hydrogen sulfide (H2S) production in diabetic BMCs improves their reparative capacities. Mouse BMCs were isolated by density-gradient centrifugation. Unilateral hind limb ischemia was conducted in 12- to 14-week-old db/+ and db/db mice by ligation of the left femoral artery. The H2S level was measured by either gas chromatography or staining with florescent dye sulfidefluor 7 AM. Both H2S production and cystathionine γ-lyase (CSE), an H2S enzyme, levels were significantly decreased in BMCs from diabetic db/db mice. Administration of H2S donor diallyl trisulfide (DATS) or overexpression of CSE restored H2S production and enhanced cell survival and migratory capacity in high glucose (HG)-treated BMCs. Immediately after hind limb ischemia surgery, the db/+ and db/db mice were administered DATS orally and/or given a local intramuscular injection of green fluorescent protein-labeled BMCs or red fluorescent protein-CSE-overexpressing BMCs (CSE-BMCs). Mice with hind limb ischemia were divided into 6 groups: db/+, db/db, db/db+BMCs, db/db+DATS, db/db+DATS+BMCs, and db/db+CSE-BMCs. DATS and CSE overexpression greatly enhanced diabetic BMC retention in ischemic hind limbs followed by improved blood perfusion, capillary/arteriole density, skeletal muscle architecture, and cell survival and decreased perivascular CD68+ cell infiltration in the ischemic hind limbs of diabetic mice. It is interesting to note that DATS or CSE overexpression rescued high glucose-impaired migration, tube formation, and survival of BMCs or mature human cardiac microvascular endothelial cells. Moreover, DATS restored nitric oxide production and decreased endothelial nitric oxide synthase phosphorylation at threonine 495 levels in human cardiac microvascular endothelial cells and improved BMC angiogenic activity under high glucose condition. Last, silencing CSE by siRNA significantly increased endothelial nitric oxide synthase phosphorylation at threonine 495 levels in human cardiac microvascular endothelial cells. Decreased CSE-mediated H2S bioavailability is an underlying source of BMC dysfunction in diabetes mellitus. Our data indicate that H2S and overexpression of CSE in diabetic BMCs may rescue their dysfunction and open novel avenues for cell-based therapeutics of critical limb ischemia in diabetic patients.

04 Relationship between erectile dysfunction and silent myocardial ischemia in diabetic patients: a multidetector computed tomography coronary angiography study

As silent myocardial ischemia (SMI) is a strong predictor of early death especially in patients with diabetes mellitus (DM), our study aims to evaluate the relationship between erectile dysfunction (ED) severity and SMI in DM patients using the multidetector computed tomography coronary angiography (MDCT-CA), and to identify predicators of SMI.

The interleukin-1β-511 T > C (rs16944) gene polymorphism is associated with risk of developing silent myocardial ischemia in diabetic patients

Silent myocardial ischemia (SMI) is a multifactorial and polygenic disorder that results from an excessive inflammatory response. Considering the prominent role of IL-1β, IL-1F10 and IL-1RN as regulators of the inflammatory process and vascular physiology, the aim of the present study was to analyze whether IL-1β, IL-1F10 and IL-1RN single nucleotide polymorphisms (SNPs) are associated with SMI. One polymorphism was associated with risk of SMI. Under co-dominant, recessive and additive models, the IL-1β-511 T>C polymorphism was associated with increased risk of SMI when compared to healthy controls (OR=4.68, 95%CI=2.21–9.92, pCCo-dom=0.0048; OR=3.97, 95%CI=1.97–7.99, pCRec=0.0024; OR=2.02, 95%CI=1.41–2.90, pCAdd=0.0024, respectively). All models were adjusted for gender, age and smoking. Linkage disequilibrium analysis showed four haplotypes (CTCC, CCTC, CCCT and CTCC) with increased frequency in SMI patients when compared to healthy controls (OR=2.53, 95%CI=1.47–4.36, pC=0.0009, OR=2.34, 95%CI=1.15–4.74, pC=0.02, OR=2.44, 95%CI=1.14–5.18, pC=0.02, OR=5.11, 95%CI=1.37–19.05, pC=0.01, respectively). In summary, our data suggest that the IL-1β-511 T>C polymorphism plays an important role in the development of SMI in diabetic patients. In addition, in our study was possible to distinguish one protective and four risk haplotypes for development of SMI.

Long-Term Clinical Outcomes of Infrapopliteal Drug-Eluting Stent Placement for Critical Limb Ischemia in Diabetic Patients

PurposeTo evaluate long-term clinical outcomes of infrapopliteal drug-eluting stent (DES) placement in insulin-dependent and non–insulin-dependent diabetic patients with critical limb ischemia (CLI). Materials and MethodsA retrospective analysis was performed of all diabetic patients treated with infrapopliteal DES between January 2002 and September 2012. The study’s primary outcome measures were patient survival and major amputation–free survival (AFS). Secondary outcome measures included technical success (defined as the creation of a straight line of blood flow to the foot arch with < 30%), identification of independent predictors of primary outcomes, infrapopliteal target limb repeat intervention–free survival, and procedure-related complications. ResultsIn total, 214 patients with CLI (168 men [78.5%]; mean age, 70 y ± 9) in 311 limbs, 562 arteries, and 679 lesions were treated. According to Kaplan–Meier analysis, survival rates were 90.8%, 55.5%, and 36.2%, and AFS rates were 94.9%, 90.4%, and 90.4%, respectively, at 1, 5, and 10 years. Target limb repeat intervention–free survival rates were 79.7%, 55.2%, and 49.7%, respectively, at 1, 5, and 10 years. The overall technical success rate was 97.7%. Cox multivariate analysis demonstrated that procedural failure was the only independent predictor of decreased AFS (hazard ratio [HR], 61.3; 95% confidence interval [CI], 13.8–271.9), and statin use was associated with increased survival (HR, 0.55; 95% CI, 0.31–0.98). Coronary disease (HR, 1.9; 95% CI, 1.01–3.54), dialysis (HR, 2.2; 95% CI, 1.21–4.06), and duration of diabetes (HR, 1.5; 95% CI, 1.02–2.34) were identified as independent predictors of decreased survival. Major complications occurred in four of 479 procedures (0.8%). ConclusionsInfrapopliteal DES placement for the management of CLI in diabetic patients resulted in a 55.5% 5-year survival rate, with a 90.4% AFS at 5 and 10 years and a 50.3% repeat intervention rate at 10 years. Technical failure was associated with reduced AFS, and statin intake was associated with increased survival.

Enhancement of Matrix Metalloproteinase 2 and 9 Inhibitory Action of Minocycline by Aspirin: An Approach to Attenuate Outcome of Acute Myocardial Infarction in Diabetes

Diabetes is a risk factor for exacerbated outcome after acute myocardial infarction (AMI) and doubles the risk of mortality after MI. Increased levels of MMP-2 and MMP-9 in diabetes cause vascular remodelling, which leads to cardiovascular complications of diabetes. We hypothesized that inhibition of MMP-2 and MMP-9 can reduce worsening of myocardial ischemia in diabetic patients. Further, we hypothesized that minocycline induced MMP-2 and MMP-9 inhibition will be potentiated by aspirin and the combination of both drugs will prevent worsening of MI in diabetic patients. In the present study, efficacy of combination of minocycline and aspirin to attenuate exacerbation of myocardial ischemia/reperfusion (I/R) injury in diabetic rats was evaluated. Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Three weeks after diabetes induction, rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of 3 weeks. At the end of week 6, I/R injury was induced by ligating the left anterior descending coronary artery for 30 min followed by 2 h reperfusion. Percentage infarct volume, arrhythmias, mortality, collagen level and MMP-2 and MMP-9 level were significantly increased in vehicle-treated diabetic group when compared with normoglycemic rats. Treatment with a combination of minocycline and aspirin decreased percentage infarct volume, arrhythmias, mortality and collagen level when compared with vehicle-treated diabetic controls and showed reduced levels of MMP-2 and MMP-9. Results of the present study suggest that the combination of minocycline and aspirin prevent worsening of AMI in diabetic rats.

Major adverse events, six months after endovascular revascularization for critical limb ischemia in diabetic patients.

This prospective study aimed to evaluate the detailed outcomes of diabetic patients with critical limb ischemia, six months after percutaneous transluminal angioplasty and appropriate multidisciplinary wound care. Totally, 45 consecutive patients (50 limbs) were enrolled and then divided into two groups according to the healing of ulcers. The endpoints were ulcer healing and major adverse events including amputation, mortality, and cardiac or cerebral morbidities, during a six- month follow-up period. During six months follow-up, major amputation was performed for four of 50 limbs (8.0%). A total of nine (20%) patients died and the leading cause was cardiac death (13.3 %). Also, stroke and non-fatal myocardial infarction occurred in three (6.7 %) and one (2.2 %) of the patients, respectively. Among the 29 (59.2 %) healed wounds, 22 (44.9 %) were completely closed. The patients with nonhealing wounds had a higher rate of dialysis (40% vs. 0 %, P-value < 0.001) and more ulcers with stage of D3 according to the Texas Wound Classification (60% vs. 31 %, P-value = 0.016). Other demographic, clinical, ulcer characteristics and procedural characteristics such as number and level of the treated lesions did not differ significantly between the two groups. Based on our findings, it seems that along with current usual therapeutic routines which focus on wound healing and limb salvage, more attention should be paid to simultaneous diagnostic assessments and treatment of cardiovascular disease in this group of patients during short-term follow- up.

Surgical treatment of lower limb ischemia in diabetic patients – long-term results

IntroductionLower limb ischemia may cause nonhealing ulcers, infection, amputation and even mortality in diabetic patients. In this study, we review our data of ischemic lower limb revascularization procedures in diabetic patients and present the early, mid- and long-term results.Material and methodsFrom March 2004 to September 2008, 83 patients with lower limb ischemia in Fontaine class III and IV underwent distal arterial bypass procedures. Saphenous vein grafts were used for below-knee arterial bypasses in all patients. In 16 (19%) patients femoropopliteal bypasses were performed with PTFE grafts. Short-term and long-term surgical results were evaluated.ResultsUlcer recovery was determined in 36% of patients. Graft patency was 95% and 1 death (1%) occurred in short-term follow-up. In long-term follow-up the total effectiveness rate was 74%. Graft patency was 79% and 6 deaths (7%) occurred during the follow-up.ConclusionsLower limb ischemia is a serious event in patients with diabetes mellitus. The consequences may include increased mortality and morbidity in this particular patient population. However, distal arterial revascularizations are considerably effective procedures to avoid amputation, to eliminate symptoms, to promote ulcer recovery and to help the patient participate in social life with acceptable short, mid- and long-term follow-up results.

Index of microvascular resistance: A new effective tool to explore microvascular disease correlated with myocardial ischemia in diabetic patients without significant coronary artery disease

Index of microvascular resistance: A new effective tool to explore microvascular disease correlated with myocardial ischemia in diabetic patients without significant coronary artery disease

Diabetic Revascularization: Endovascular Versus Open Bypass—Do We Have the Answer?

Diabetes is an independent risk factor for peripheral arterial disease and, when advanced peripheral arterial disease develops in the setting of diabetes, it portends a greatly increased threat to both life and limb. The management of severe limb ischemia in diabetic patients, particularly those with tissue loss and infection, remains a major surgical challenge in the new millennium. However, advances in multidisciplinary care, including an aggressive revascularization approach, can avoid major amputation in a large percentage of patients. The unique pattern of lower extremity atherosclerosis in diabetes is a critical determinant of the revascularization strategy. Most diabetics with critical ischemia have popliteal/tibial occlusions requiring below-the-knee intervention or bypass grafting. Bypass surgery with vein to crural or pedal arteries remains the gold standard of revascularization, but may be limited by patient risk, conduit availability, and a suitable target. Infrapopliteal angioplasty can have acceptable results for suitable lesions, particularly when there is not extensive tissue loss in the foot. However, restenosis rates after endovascular intervention in these vessels are high, and recent advances in drug-eluting balloons and stents have promise but remain largely unproven. There is limited high-quality evidence to support treatment choices in this arena, with only one randomized clinical trial to date. The available data suggest that patients with life expectancy of at least 2 years and more extensive disease have superior outcomes with open reconstruction. A selective revascularization strategy is advocated, using autogenous vein bypass as the initial approach in a significant percentage of patients, based on its greater overall efficacy and proven durability. However, endovascular therapies have an important role in current practice, which will increase further if restenosis can be overcome. Vascular specialists should understand and be able to apply both types of interventions to optimize patient outcomes.