Diabetic Peripheral Arterial Disease Research Articles

Vitamin D3 metabolite ratio as an indicator of vitamin D status and its association with diabetes complications

BackgroundVitamin D deficiency is diagnosed by total serum 25-hydroxyvitamin D (25(OH)D) concentration and is associated with poor health and increased mortality; however, some populations have low 25(OH) D concentrations without manifestations of vitamin D deficiency. The Vitamin D Metabolite Ratio (VMR) has been suggested as a superior indicator of vitamin D status. Therefore, VMR was determined in a population with type 2 diabetes at high risk for vitamin D deficiency and correlated with diabetic complications.Research design and methodsFour hundred sisty patients with type 2 diabetes (T2D) were recruited, all were vitamin D3 supplement naive. Plasma concentration of 25-hydroxyvitamin D3 (25(OH)D3) and its metabolites 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and its epimer, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), were measured by LC-MS/MS analysis. VMR-1 was calculated as a ratio of 24,25(OH)2D3:25(OH)D3; VMR-2 as a ratio of 1,25(OH)2D3:25(OH)D3; VMR-3 was calculated as a ratio of 3-epi-25(OH)D3: 25(OH)D3.ResultsAn association means that there were significant differences between the ratios found for those with versus those without the various diabetic complications studied. VMR-1 was associated with diabetic retinopathy (p = 0.001) and peripheral artery disease (p = 0.012); VMR-2 associated with hypertension (p < 0.001), dyslipidemia (p < 0.001), diabetic retinopathy (p < 0.001), diabetic neuropathy (p < 0.001), coronary artery disease (p = 0.001) and stroke (p < 0.05). VMR-3 associated with hypertension (p < 0.05), dyslipidemia (p < 0.001) and coronary artery disease (p < 0.05).ConclusionsIn this cross sectional study, whilst not causal, VMR-2 was shown to be the superior predictor of diabetic and cardiovascular complications though not demonstrative of causality in this cross-sectional study population over VMR-1, VMR-3 and the individual vitamin D concentration measurements; VMR-2 associated with both microvascular and cardiovascular indices and therefore may have utility in predicting the development of diabetic complications.

Socioeconomic Distressed Communities Index Associated with Higher Burden of Amputation in Diabetic Peripheral Arterial Disease

Category:Diabetes; OtherIntroduction/Purpose:The prevalence of diabetes and one of its complications, peripheral arterial disease (PAD), is increasing. Diabetic PAD is known to lead to high rates of lower extremity amputations. Diabetes disproportionately affects people of low socioeconomic status. The Distressed Community Index (DCI) is a proxy social risk factor, calculated at the zip code level as a function of seven metrics of community economic well-being: no high school diploma, housing vacancy rate, unemployment rate, poverty rate, median income ratio, change in employment, and change in establishments. Higher DCI has been linked to longer operative times, longer hospital length of stay, and increased incidence of postoperative complications. This analysis sought to analyze the impact of a socioeconomic risk factor, DCI, on amputation rate in patients with diabetic PAD.Methods:Data from a regional hospital abstract reporting system was obtained from the State Department of Health. It was sorted to include patient records with a diagnosis of peripheral arterial disease (ICD-10-CM diagnostic codes). Data was further stratified by diagnosis of diabetic PAD and DCI score. DCI scores were obtained from the Economic Innovation Group.Procedure codes were used to identify amputations starting with ‘detachment at [R/L] foot, complete, open approach’ and including all progressively distal amputations (ICD-10-PCS codes). Statistical analysis was performed using XLSTAT, significance was assigned at alpha of 0.05.Results:From 2016 to 2018, there were 33664 patients requiring inpatient treatment with a diagnosis of PAD. 13261 patients (39.4%) had diabetic PAD, 3078 patients (9.1%) originated from a zip code with a DCI score greater than or equal to 75 (top quartile) and 1394 patients (4.1%) had diabetic PAD and DCI greater than 75. While patients with diabetic PAD and a DCI less than 75 had approximately the same rate of amputations as all patients with diabetic PAD (15.3% and 15.7%, respectively), patients with diabetic PAD and a DCI greater than 75 were 1.30 times more likely (p=0.0003) to require amputation than all patients with diabetic PAD (19.1% and 15.7% overall amputation rates, respectively). The relationship with DCI was not significant in non- diabetic PAD patients.Conclusion:Approximately one in five patients presenting for inpatient treatment with a diagnosis of diabetic PAD originating from a zip code with a DCI score greater than or equal to 75 required a lower extremity amputation. Though diabetes by itself was a stronger risk factor for amputation (OR 8.24, p<0.0001) than DCI in the comprehensive PAD patient population, a patient with a high DCI score in the diabetic PAD population was significantly more likely to require amputation. DCI is a proxy social risk factor providers can use to preemptively identify patients at increased risk of lower extremity amputation secondary to PAD.

A Comparison of Revascularization Methods for Peripheral Arterial Disease in Diabetics: Changing Trends in Lower Extremity Revascularization from 2008-2014

A Comparison of Revascularization Methods for Peripheral Arterial Disease in Diabetics: Changing Trends in Lower Extremity Revascularization from 2008-2014

New public health policy intervention for diabetic foot management in Mexico

Abstract Problem In Mexico, an estimated 12 million people have diabetes, with complications of diabetes contributing to 25-90% of non-traumatic amputations. Description of the Problem We conducted a review through the literature of available studies in English-language databases and libraries, including PubMed and UNAM digital Library to determine the role of teaching first contact health workers and the creation of limb salvage teams in the prevention of amputations. Through this review, we present the basis of our proposal about implementing these strategies to improve a care coordination system for diabetic foot management in Mexico. Results There were 25 publications from different countries, 12 eligible for this review. The review emphasizes that the creation of Specialized Diabetic Foot Teams to treat patients and teach first contact medical workers could help to achieve the following objectives which result in the reduction of amputations and improved patient outcomes: Standardize and simplify the diabetic foot clinical examination. Timely reference of patients with DM with a moderate and high risk of diabetic foot complications. Timely reference of patients with diabetic foot and peripheral arterial disease to third-level hospitals. Periodic first-contact health workers training on risk detection and stratification of diabetic foot. Lessons Implementing the policy of creation of Specialized Diabetic Foot Teams to treat patients and teach first contact medical workers will contribute to reducing major amputations due to diabetes in our country. We aim to implement a successful policy in Mexico to strengthen the health system and improve outcomes and therefore the quality of life of patients with diabetic foot complications. We aim to serve as a legislative voice for all patients in Mexico facing major amputations and other diabetes complications. Key messages New public health policy implementation for diabetic foot management in Mexico. Prevention of major amputations.

Diabetic foot syndrome

Diabetic foot syndrome Abstract. Although a common and relevant complication of diabetes mellitus, diabetic foot syndrome still remains underdiagnosed. As major risk factors, diabetic peripheral neuropathy and peripheral artery disease play a central role. Prevention of diabetic foot ulceration and diabetic foot infection is the cornerstone of care, pointing to the importance of patients and care givers education in regularly inspecting and examining the "foot at risk". In addition to already well implemented screening programs for retinopathy and nephropathy in patients with diabetes mellitus, guidelines must also focus on diabetic foot care. The Swiss guidelines help identifying the patient at risk and direct adequate management. Management of the diabetic foot is complex. The appropriate and immediate treatment involves healthcare professionals of different specialties. Therefore, a multidisciplinary team approach is highly recommended. The major objectives are to reduce complications, such as amputations, morbidity and mortality - and, last but not least, the economic burden of the disease.

The influence of simultaneous pancreas-kidney transplantation on the evolution of diabetic foot lesions and peripheral arterial disease

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Prospective observational study evaluating association of sociodemographic parameters, Wagner’s grading, peripheral arterial disease and diabetic peripheral neuropathy with the outcomes of diabetic foot ulcers

Background: The present study was conducted to determine the association of sociodemographic parameters, comorbid conditions and complications of diabetes mellitus (DM) with the treatment outcomes of diabetic foot ulcers.Methods: The present prospective observational study enrolled 105 participants aged 30-85 years with diabetic foot ulcers presenting to general surgery department during a period of 18 months. Participants who were terminally ill, who had trophic ulcers of Hansen’s disease and filariasis and its sequelae were excluded. The study was approved by institutional ethics committee and written informed consent was obtained from all study participants. Data was analyzed using R and the test of significance was chi square test, p&lt;0.05 was considered statistically significant.Results: Higher proportion of male participants and those aged between 50-69 years were encountered. Male participants were of higher age and the mean duration of DM in participants with diabetic foot ulcer was 8 years. The mean HbA1C of study participants was 8.1%, 38.1% participants had high plasma glucose. Food deformity was observed in 41% participants. 62.9% and 66.7% participants had diabetic peripheral neuropathy and peripheral arterial disease respectively. The mean time required for healing among participants with diabetic foot ulcers was 45.8 Significant association of major amputation with diabetic peripheral neuropathy (p=0.02), Wagner’s grading (p&lt;0.001) and peripheral arterial disease (PAD) (p=0.006) was observed.Conclusions: The presence of diabetic peripheral neuropathy and PAD were risk factors for major amputations in diabetic foot ulcers. Lower Wagner’s grading was associated with lower chances of major amputation.

Prevalence and risk factors of diabetic peripheral neuropathy in a diabetics cohort: Register initiative “diabetes and nerves”

ObjectiveThe aim of this study was to assess the prevalence of diabetic peripheral neuropathy (DPN) and associated risk factors among patients with type 1 (T1D) and type 2 diabetes (T2D). MethodsA total of 141 patients with T1D and 844 patients with T2D mostly from primary care practices were enrolled in our register initiative. DPN was assessed using the Neuropathy Symptom Score (NSS) and Neuropathy Deficit Score (NDS). Data were analyzed by bivariate and multivariate logistic regression. ResultsThe overall prevalence of DPN in the cohort was 40.3% [95% CI: 37.3-43.3%], 29.1% [22.0-36.9%] among patients with T1D and 42.2% [38.9-45.6%] with T2D (p<0.005). DPN prevalence increased with age from 11.9% [4.5-20.9%] aged ≤40 years up to >50% [47.7-57.5%] aged >70 years (p<0.001). The diabetes duration subclassification revealed a high DPN-prevalence of 35% [15.0-55.0%] among patients with T2D at time of diagnosis. A significant increase of prevalence was present 5 and 25 years following T1D and 25 years following T2D diagnosis (p<0.001). DPN risk factors were “older age” (OR [95% CI]: 1.05 [1.02-1.08], p<0.005) and loss of consciousness due to severe hypoglycemia episodes (OR [95% CI]: 10.28 [1.70-62.01], p<0.05) for T1D and “older age” (OR [95% CI]: 1.02 [1.00-1.04], p=0.056) and the presence of a cardiovascular-metabolic profile (obesity, hypertension, low HDL-c levels, elevated triglycerides, low physical activity and limited range of motion) for T2D. Furthermore, co-morbidities such as diabetic nephropathy (OR [95% CI]: 1.92 [1.14-3.22]), retinopathy (OR [95% CI]: 1.87 [1.10-3.18]) and peripheral artery disease (OR [95% CI]: 1.81 [1.07-3.08]) were independently associated with DPN (p<0.05). ConclusionsHigh rates of DPN among outpatients with diabetes suggest the need for early screening, especially in individuals that present with a plethora of co-morbidities. Diabetes treatment regimens that preclude a cardiovascular-metabolic risk profile and episodes of severe hypoglycemia should be sought, given that such episodes are more common among patients suffering from DPN.

597-P: Prolonged Therapeutic Effects of Photoactivated Adipose-Derived Stem Cells following Diabetic Ischemic Injury

Aim: Adipose-derived stem cells (ADSCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. Methods: Cultured ADSCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Photoactivated and non-light-treated ADSCs were injected into the tail vein of mice fed a high-fat diet (HFD), following which unilateral hindlimb ischemia was induced. Laser Doppler imaging was conducted to measure the blood flow reperfusion. Capillary density was measured in the ischemic gastrocnemius muscle. mRNA levels of angiogenic factors were determined by reverse-transcription polymerase chain reaction, Flow cytometry was used to determine the characterization of ADSCs and endothelial progenitor cell (EPC). Human ADSCs secretomes were analyzed by liquid chromatography tandem mass spectrometry. Results: Our study demonstrated that photoactivated ND-ADSCs prolonged functional blood flow perfusion and increased ADSCs-derived EPC and neovascularization thirty-eight days after ligation, when compared with saline-treated controls. Profiling analysis in ischemic muscles showed upregulation of genes associated with pro-angiogenic factors after injection of photoactivated ND-ADSCs when compared with the non-light-treated ADSCs or saline treated HFD mice. Mass spectrometry revealed that light-treated ADSCs conditioned medium retained a more complete pro-angiogenic activity with significant upregulation of angiogenesis related proteins. Conclusion: Our data demonstrates that photoactivated ND-ADSCs improve blood flow recovery and their injection may prove to be a useful strategy for the prevention and treatment of diabetic peripheral arterial disease. Disclosure X. Fan: None. J. Wu: Research Support; Self; HarmonyRegena Inc.

VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs

BackgroundNew therapies to treat diabetic peripheral artery disease (PAD) require target-specific non-invasive imaging modalities to follow efficacy. As a translational study, we performed targeted imaging of receptors for vascular endothelial growth factor (VEGF) in response to anterior femoral artery occlusion (FAO) in Yucatan minipigs and compare the normal response to response in diabetic Yucatan minipigs.MethodsEleven Yucatan minipigs, 6 non-diabetic (non-D) and 5 purpose bred diabetic (D) (Sinclair, Auxvasse MO), underwent intravascular total occlusion of the anterior femoral artery (FA). At days 1 and 28, pigs underwent SPECT/CT 201Tl hindlimb perfusion imaging and at day 7 were injected with [99mTc]DOTA-PEG-scVEGF (scV/Tc) tracer targeting VEGF receptor, and underwent biopsies of the hindlimb muscles for gamma counting and histology, followed by imaging. One day after the final scan, pigs underwent contrast angiography of the lower extremities. Counts from scans were converted to percentage injected activity (%IA).ResultsPerfusion was lower in the occluded hindlimb compared to non-occluded on day 1 in both the D and non-D pigs. At day 7, scV/Tc count ratio of counts from ROIs drawn in proximal gastrocnemius muscle for the occluded over non-occluded limb was significantly higher in non-D vs. D pigs (1.32 ± 0.06 vs. 1.04 ± 0.13, P = 0.02) reflecting higher level of angiogenesis. Perfusion increased between days 1 and 28 in the muscles in the occluded limb for the non-diabetic pigs while the diabetic pig showed no increase (+ 0.13 ± 0.08 %IA vs. − 0.13 ± 0.11, P = 0.003). The anterior FA showed poor contrast filling beyond occluder and qualitatively fewer bridging collaterals compared to non-D pigs at 28 days.ConclusionVEGF receptor targeted imaging showed the effects of diabetes to suppress angiogenesis in response to occlusion of the anterior femoral artery of purpose bred diabetic Yucatan minipigs and indicates potential applicability as a marker to follow efficacy of novel therapies to improve blood flow by stimulating angiogenesis in diabetic PAD.

Prolonged therapeutic effects of photoactivated adipose-derived stem cells following ischaemic injury.

Adipose-derived stem cells (ASCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Unilateral hindlimb ischaemia model was induced in high-fat diet (HFD)-fed mice by femoral artery interruption, after which photoactivated and non-light-treated ASCs were injected into the tail vein of mice. Laser Doppler imaging was conducted to measure the blood flow reperfusion. Capillary density was measured in the ischaemic gastrocnemius muscle. mRNA levels of angiogenic factors were determined by reverse-transcription polymerase chain reaction. Flow cytometry was used to determine the characterization of ASCs and endothelial progenitor cell (EPC). Human ASCs secretomes were analysed by liquid chromatography tandem mass spectrometry. Our study demonstrated that photoactivated ND-ASCs prolonged functional blood flow perfusion and increased ASCs-derived EPC and neovascularization 38days after ligation, when compared with saline-treated controls. Profiling analysis in ischaemic muscles showed upregulation of genes associated with pro-angiogenic factors after injection of photoactivated ND-ASCs when compared with the non-light-treated ASCs or saline treated HFD mice. Mass spectrometry revealed that light-treated ASCs conditioned medium retained a more complete pro-angiogenic activity with significant upregulation of angiogenesis related proteins. Our data demonstrates that photoactivated ND-ASCs improve blood flow recovery and their injection may prove to be a useful strategy for the prevention and treatment of diabetic peripheral arterial disease.

Reduced Sirtuin1 signalling exacerbates diabetic mice hindlimb ischaemia injury and inhibits the protective effect of a liver X receptor agonist

Diabetes mellitus causes endothelial dysfunction, which further exacerbates peripheral arterial disease (PAD). Improving endothelial function via reducing endothelial oxidative stress (OS) may be a promising therapy for diabetic PAD. Activation of liver X receptor (LXR) inhibits excessive OS and provides protective effects on endothelial cells in diabetic individuals. Therefore, we investigated the effects of LXR agonist treatment on diabetic PAD with a focus on modulating endothelial OS. We used a streptozotocin‐induced diabetes mouse model combined with a hindlimb ischaemia (HLI) injury to mimic diabetic PAD, which was followed by LXR agonist treatment. In our study, the LXR agonist T0901317 protected against HLI injury in diabetic mice by attenuating endothelial OS and stimulating angiogenesis. However, a deficiency in endothelial Sirtuin1 (SIRT1) largely inhibited the therapeutic effects of T0901317. Furthermore, we found that the underlying therapeutic mechanisms of T0901317 were related to SIRT1 and non‐SIRT1 signalling, and the isoform LXRβ was involved in LXR agonist‐elicited SIRT1 regulation. In conclusion, LXR agonist treatment protected against HLI injury in diabetic mice via mitigating endothelial OS and stimulating cellular viability and angiogenesis by LXRβ, which elicited both SIRT1‐mediated and non‐SIRT1‐mediated signalling pathways. Therefore, LXR agonist treatment may be a promising therapeutic strategy for diabetic PAD.

In peripheral artery disease, diabetes is associated with reduced physical activity level and physical function and impaired cardiac autonomic control: A cross-sectional study.

Diabetes has been considered a major risk factor for peripheral artery disease (PAD). The effect of diabetes on daily physical activity level and cardiovascular function in PAD patients is poorly known. To analyze the effect of diabetes on physical activity level, physical function and cardiovascular health parameters in patients with PAD and claudication symptoms. Cross-sectional study of 267 PAD patients, 146 without and 121 with diabetes. Physical activity levels were objectively measured by using an accelerometer, and time spent in sedentary (0-100 counts/min), light (101-1040 counts/min) and moderate to vigorous (≥1041 counts/min) physical activity was obtained. Physical function assessment included the 6-min walk test, handgrip strength test and short physical performance battery. Cardiovascular health parameters measured were brachial blood pressure, heart rate variability, and arterial stiffness. Diabetic PAD patients spent more time in sedentary behavior (P=0.001, effect size [ES] 0.234) and less time in light (P=0.003, ES=0.206) and moderate-to-vigorous physical activity (P<0.001, ES=0.258) than non-diabetic PAD patients. Diabetic PAD patients presented lower 6-min walk distance (P=0.005, ES=0.194) and impaired cardiac autonomic modulation (standard deviation of all NN intervals [SDNN], P<0.001, ES=0.357; square root of the mean of the sum of the squares of differences between adjacent NN intervals [RMSSD], P<0.001, ES=0.280; and NN50 count divided by the total number of all NN intervals [pNN50], P<0.001, ES=0.291) as compared with non-diabetic PAD patients. After adjustment for confounders, diabetes remained associated with sedentary behavior (P=0.011), light (P=0.020) and moderate-to-vigorous physical activity (P=0.008), 6-min walk distance (P=0.030), SDNN (P<0.001), RMSSD (P=0.004), and PNN50 (P=0.004). Diabetic PAD patients presented lower physical activity level, reduced physical function and impaired autonomic modulation as compared with non-diabetic PAD patients.

Amputation-free survival in patients with diabetic foot ulcer and peripheral arterial disease: Endovascular versus open surgery in a propensity score adjusted analysis

AimsThe aim of the present study was to compare outcomes of endovascular surgery versus open vascular surgery in patients with diabetic foot ulcer (DFU) and peripheral arterial disease (PAD). MethodsBetween 1984 and 2006, 1151 patients with DFU were admitted to the diabetic foot care team. Three hundred seventy-six patients with 408 limbs were consecutively included at a multidisciplinary foot center, 289 limbs were treated with endovascular surgery and 119 limbs with open vascular surgery first strategy. A propensity score adjusted analysis was performed to compare outcomes for type of revascularization. ResultsMajor amputation rates at 3 years were 17.0% and 16.8% (p = 0.97) and mortality at 3 years were 43.1% and 46.5% (p = 0.55) after endovascular surgery and open vascular surgery, respectively. In the propensity score adjusted analysis, patients undergoing endovascular surgery first had similar outcomes in terms of major amputation, mortality, combined major amputation/mortality compared to those undergoing open vascular surgery. Longer time to intervention (p = 0.003) was associated with increased major amputation rate in the multivariable Cox regression analysis. ConclusionThe endovascular surgery first and open vascular surgery first strategies were associated with similar long-term results in a large cohort of patients with DFU and PAD undergoing revascularization. Rapid revascularization reduces the risk of amputation.

Accuracy of non‐contrast quiescent‐interval single‐shot and quiescent‐interval single‐shot arterial spin‐labelled magnetic resonance angiography in assessment of peripheral arterial disease in a diabetic population

Diabetic patients with peripheral arterial disease (PAD) are challenging to assess. Non-contrast magnetic resonance angiography (MRA) offers a safe alternative in patients with renal impairment. The study objective is to evaluate accuracy of lower limb quiescent-interval single-shot (QISS) MRA and pedal QISS-arterial spin-labelled (ASL) MRA for detection of significant stenosis in diabetic patients with PAD. Combined QISS and QISS-ASL MRA was performed in 32 diabetic PAD patients (20 male, 12 female; mean 69years; 8 with critical ischaemia). Two readers assessed haemodynamically significant (>50%) stenosis and diagnostic confidence on MRA, against digital subtraction angiography (DSA) as the reference standard, with subgroup analysis of patients with severe renal impairment (n=7). Inter-reader agreement of stenosis and diagnostic confidence were evaluated. Test-retest reproducibility was evaluated in 10 subjects who underwent repeat MRA on a different day. At DSA, 262/645 segments (40.6%) had haemodynamically significant stenoses. MRA accuracy was 78.1% (478/612) and 75.6% (464/614), sensitivity 64.7% (161/249) and 77.5% (193/249), and specificity 87.3% (317/363) and 74.2% (271/365) for 2 readers. MRA accuracy was 80.9% and 80.7% for readers 1 and 2, respectively, in patients with severe renal impairment. QISS MRA but not pedal QISS-ASL MRA was considered of diagnostic image quality. Inter-reader agreement was moderate for stenosis (ĸ=0.60) and diagnostic confidence (ĸ=0.41). Test-retest reproducibility was high (ĸ=0.87) and moderate (ĸ=0.54) for individual readers. Quiescent-interval single-shot MRA has reasonable accuracy in a diabetic PAD population with high burden of disease, providing a non-contrast option in patients with renal impairment. QISS-ASL MRA requires further optimisation to be clinically feasible.

Smooth muscle SIRT1 reprograms endothelial cells to suppress angiogenesis after ischemia

Objective: Vascular smooth muscle cells (VSMCs) undergo the phenotypic changes from contractile to synthetic state during vascular remodeling after ischemia. SIRT1 protects against stress-induced vascular remodeling via maintaining VSMC differentiated phenotype. However, the effect of smooth muscle SIRT1 on the functions of endothelial cells (ECs) has not been well clarified. Here, we explored the role of smooth muscle SIRT1 in endothelial angiogenesis after ischemia and the underlying mechanisms.Methods: We performed a femoral artery ligation model using VSMC specific human SIRT1 transgenic (SIRT1-Tg) and knockout (KO) mice. Angiogenesis was assessed in in vivo by quantification of the total number of capillaries, wound healing and matrigel plug assays, and in vitro ECs by tube formation, proliferation and migration assays. The interaction of HIF1α with circRNA was examined by using RNA immunoprecipitation, RNA pull-down and in situ hybridization assays.Results: The blood flow recovery was significantly attenuated in SIRT1-Tg mice, and markedly improved in SIRT1-Tg mice treated with SIRT1 inhibitor EX527 and in SIRT1-KO mice. The density of capillaries significantly decreased in the ischemic gastrocnemius of SIRT1-Tg mice compared with SIRT1-KO and WT mice, with reduced expression of VEGFA, which resulted in decreased number of arterioles. We identified that the phenotypic switching of SIRT1-Tg VSMCs was attenuated in response to hypoxia, with high levels of contractile proteins and reduced expression of the synthetic markers and NG2, compared with SIRT1-KO and WT VSMCs. Mechanistically, SIRT1-Tg VSMCs inhibited endothelial angiogenic activity induced by hypoxia via the exosome cZFP609. The cZFP609 was delivered into ECs, and detained HIF1α in the cytoplasm via its interaction with HIF1α, thereby inhibiting VEGFA expression and endothelial angiogenic functions. Meantime, the high cZFP609 expression was observed in the plasma of the patients with atherosclerotic or diabetic lower extremity peripheral artery disease, associated with reduced ankle-brachial index. Knockdown of cZFP609 improved blood flow recovery after hindlimb ischemia in SIRT1-Tg mice.Conclusions: Our findings demonstrate that SIRT1 may impair the plasticity of VSMCs. cZFP609 mediates VSMCs to reprogram endothelial functions, and serves as a valuable indicator to assess the prognosis and clinical outcomes of ischemic diseases.

Diabetic Foot and Peripheral Arterial Disease – The Worst Combination!

Abstract not available&#x0D; J Bangladesh Coll Phys Surg 2020; 38(1): 3-4

Managing Peripheral Artery Disease in Diabetic Patients: A Questionnaire Survey from Vascular Centers of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS)

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded on October 1, 2018, to enhance cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic arteriopathy has been selected as the very first topic to be investigated by the federation. MeFAVS members were asked to reply to a questionnaire on the management of diabetic ischemic foot. Results were collected and analyzed statistically. The questionnaire consisted of 15 multiple choice answers regarding diabetic foot (DF) diagnosis and treatment. The questionnaire was submitted to 21 centers on April 20,2019. Response rate was 62%. The survey revealed that vascular surgeons, diabetologists, and wound care nurses made-up the core of the diabetic teams present in 76.9%, 69.3%, and 92.3% of the centers, respectively. Diabetic teams were most often led by vascular surgeons (53.8%) and diabetologists (42.2%), but only in 7.9% of cases by nurses. Duplex ultrasonography and computed tomographic angiography were the most commonly available tools used to assess diabetic peripheral arterial disease (PAD). Surgical wound care was undertaken by vascular surgeons in the majority of cases, and only in 46.2% of the cases to orthopedic or plastic surgeons, while nonsurgical wound care was handled by specialized nurses (76.6%) and diabetologists (53.8%). First-line revascularization was preferred over conservative treatment (61.5% vs 53.8%) and endovascular strategy (45.3%) over open (33.7%) or hybrid (21.0%) surgery. Vascular surgeons and interventional radiologists were found to be the most common performers of endovascular revascularization (92.3% and 53.8%, respectively). Amputations had an overall rate of 16.6% (range 4-30%) and a mean reintervention rate of 22.5%, and were usually performed by vascular surgeons for both minor and major interventions (84.6%) followed by orthopedic surgeons (15.4% minor and 30.8% major). The availability of a DF clinic (84.6%) and endovascular (53.8%) and open surgery (46.2%) capabilities were considered fundamental to reduce amputation rates. Especially since the introduction and spreading of new endovascular techniques for the treatment of DF, it is a common consensus amongst vascular surgeons that a standardized approach to the discipline is necessary in order to improve outcomes such as amputation-free survival and mortality and it is with this perspective and purpose that transnational cooperation amongst vascular professionals and residents in training are aiming for greater proficiency in endovascular and open surgery.

Prevalence of peripheral neuropathy and peripheral artery disease in diabetic patients attending a tertiary care hospital

Background: Foot complications are one of the most devastating complications among diabetes all over the world. Both Diabetic Peripheral Neuropathy (DPN) and Peripheral Artery Disease (PAD) are responsible for diabetic foot complications. Aim of this study is to screen diabetic patients for both DPN and PAD.Methods: This is a cross-sectional study covering 200 diabetic patients attending a Teaching Hospital. Prevalence of DPN was assessed using Biothesiometer and PAD by measuring the Ankle Brachial Index using handheld Doppler.Results: 49.5% had DPN and 19.5% had PAD. 13% had both PAD and DPN. Most of the subjects were in 51-60 years age group constituting 36.5 %. 61.5% were females. 69.5% had diabetes for more than 10 years. 88% had their HbA1C of more than 6.5%.Conclusions: The prevalence of PVD is multi-fold higher in patients with diabetes with smoking, hyperglycemia, hypertension, dyslipidemia, as major risk factors. Ankle, brachial pressure index, is useful in identifying PVD and it needs further evaluation by an arterial color Doppler and digital subtraction angiography.

RISK FACTORS FOR DIABETIC FOOT AND LOWER LIMB AMPUTATION

Introduction: Diabetic foot syndrome (DFS) is the major cause of hospitalization for diabetes-related complications. Protective sensation loss and impaired vision increase the susceptibility for minor feet trauma, which results in diabetic foot ulceration with or without subsequent infection. Peripheral arterial disease is a major cause of impaired ulcer, wound healing and gangrenous diabetic foot. The most important intervention to prevent diabetic foot ulceration and its consequences is early recognition of high-risk patients and their risk factors and referral to appropriate medical departments. There are various risk factors for major lower extremity amputations related to diabetic foot, which includes microvascular diseases, infections, long duration of diabetes, poor glycemic control, peripheral arterial disease, old age and associated cardiovascular comorbidities.&#x0D; Material and Methods: This study was done on the review of medical records of consecutive type 2 diabetic patients. Admitted patients were treated and managed according to the standard protocol of the hospital. History, clinical and physical examination were carried out on each patient. Ulcer characteristics like infection and depth of the ulcer, site of ulcer were assessed. Associated diabetic neuropathy and peripheral arterial disease was assessed by a clinical method. Age, sex, body mass index (BMI), smoking, duration of diabetes, diabetic control therapy, associated hypertension, cardiac diseases were recorded. The glycated haemoglobin level (HbA1c) were recorded.&#x0D; Results: A total of 128 patients with diabetic foot were included in the study of which 76(59.4%) were male and 52(40.6%) were female. Of the 76 male 6 (4.7%) had major amputation and out of 52 female 4(3.1%) had major amputation, thus total number of major amputations were 10(7.8%). Statistically significant difference was observed in HbA1C and duration of diabetes group in amputation. High HbA1C and more duration of diabetes was associated with the higher number of amputation. The rate of amputation was much higher among patients hypertension, smoking, cardiac diseases and stroke. Conclusion: Poor glycemic controls and duration of diabetes are the important independent risk factors for diabetes-related major lower extremity amputations.&#x0D; Keywords: DFS, BMI, smkoing, DM