The vascular complications of diabetes: a review of their management, pathogenesis, and prevention.

INTRODUCTION: This review highlights the pathogenesis of both microvascular and macrovascular complications of diabetes and how these mechanisms influence both the management and preventative strategies of these complications. The cumulative data shown in this review suggest hyperglycemic and blood pressure control remain central to this intricate process. AREAS COVERED: We reviewed the literature including retrospective, prospective trials as well as meta-analysis, and post hoc analysis of randomized trials on microvascular andmacrovascular complications. EXPERT OPINION: Further research is needed to explore the ideal intervention targets and preventative strategies needed to prevent macrovascular complications. Furthermore, as the data for trials looking at microvascular complications lengthen more long-term data will further elucidate the role that the duration of diabetes has on these complications. Additionally, trials looking to maximize hyperglycemic control with multiple agents in diabetes, such as metformin, SGL2isand GLP-1 receptor agonists are currently in process, which will have implications for rates of microvascular as well as macrovascular complications.

Protective Factors and the Pathogenesis of Complications in Diabetes.

Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of microvascular and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid (both vascular and parenchymal) tissue origin, since the profile of diabetes complications ranges from those involving only vascular tissues to those involving mostly parenchymal organs. A major paradigm shift has occurred in recent years regarding the pathogenesis of diabetes complications, in which the focus has shifted from studies on risks to those on the interplay between risk and protective factors. While risk factors are clearly important for the development of chronic complications in diabetes, recent studies have established that protective factors are equally significant in modulating the development and severity of diabetes complications. These protective responses may help explain the differential severity of complications, and even the lack of pathologies, in some tissues. Nevertheless, despite the growing number of studies on this field, comprehensive reviews on protective factors and their mechanisms of action are not available. This review thus focused on the clinical, biochemical, and molecular mechanisms that support the idea of endogenous protective factors, and their roles in the initiation and progression of chronic complications in diabetes. In addition, this review also aimed to identify the main needs of this field for future studies.

Walking pace and microvascular complications among individuals with type 2 diabetes: A cohort study from the UK Biobank.

INTRODUCTION: Walking pace is associated with various health-related outcomes. The aim of this study was to investigate the association between self-reported walking pace and the incidences of diabetic microvascular complications among participants with type 2 diabetes (T2D). METHODS: Self-reported walking pace was classified as brisk, average, or slow. The outcomes were the incidences of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A total of 14 518 participants with T2D in the UK Biobank (mean age 59.7 ± 7.0 years, 5028 [34.6%] women) were included. During a median follow-up of 12.5 (interquartile range: 11.6-13.4) years, 2980 participants developed diabetic microvascular complications. After adjusting for confounding factors, and compared with brisk walkers, slow walkers had a multivariable-adjusted HR of 1.98 (95% CI 1.58, 2.47) for composite diabetic microvascular complications, 1.54 (95% CI 1.11, 2.14) for diabetic retinopathy, 3.26 (95% CI 2.08, 5.11) for diabetic neuropathy, and 2.32 (95% CI 1.91, 2.82) for diabetic nephropathy. Average walking pace was associated with a higher risk for diabetic nephropathy (HR 1.51, 95 CI% 1.27-1.79) compared with brisk walking. Additionally, ≥1 diabetic microvascular complication occurred in 447 (14.7%) of participants with brisk walking pace, 1702 (19.5%) with average walking pace, and 831 (30.4%) with slow walking pace. Time from study recruitment to first diagnosis was shorter in participants who reported a slow walking pace, compared with brisk or average walkers. Among participants who had diabetic nephropathy as their first diagnosis, slow walking pace was associated with subsequent risk of a second diabetic microvascular complication (HR 3.88, 95 CI% 2.27-6.60). CONCLUSIONS: Self-reported slow walking pace is associated with a higher risk of diabetic microvascular complications among participants with T2D in this population-based cohort study.

Serum albumin and risk of incident diabetes and diabetic microvascular complications in the UK Biobank cohort.

AIM: To examine the associations between serum albumin and the incidences of diabetes and diabetic microvascular complications in participants of the UK Biobank cohort. METHODS: There were 398,146 participants without diabetes and 30,952 patients with diabetes from the UK Biobank cohort included in this study. Multivariate-adjusted Cox proportional hazard models were used to analyze the association of albumin with the incidences of diabetes and diabetic microvascular complications. Mendelian randomization (MR) analysis was used to determine the genetic relationships between serum albumin and diabetes. RESULTS: After a median 12.90 years follow-up, 14,710 participants developed incident diabetes (58.83 ± 7.52 years, 56.10% male). After multivariate adjustment, serum albumin was inversely associated with incident diabetes: hazard ratio (HR) [95% confidence interval] per 10 g/l increase 0.88 [0.82;0.94]. MR analyses suggested a potential genetic influence of serum albumin on diabetes in both the UK Biobank and the FinnGen consortium: odds ratios (ORs) [95% confidence interval per 1 g/l increase 0.99 [0.98;1.00] and 0.78 [0.67;0.92], respectively. In patients with diabetes, higher serum albumin levels were significantly associated with lower risk for diabetic microvascular complications. Specifically, per 10 g/l increase in serum albumin, the HRs for diabetic nephropathy, ophthalmopathy, and neuropathy were 0.42 [0.30;0.58], 0.61 [0.52;0.72], and 0.67 [0.51;0.88], respectively. CONCLUSION: In this large prospective study, serum levels of albumin were inversely associated with the incidences of diabetes and diabetic microvascular complications. These findings underscore the importance of maintaining optimal nutrient status in reducing the risk of diabetes and its complications.

Glucose variability: a new risk factor for cardiovascular disease.

AIMS AND DATA SYNTHESIS: Glucose variability (GV) is increasingly considered an additional index of glycemic control. Growing evidence indicates that GV is associated with diabetic vascular complications, thus being a relevant point to address in diabetes management. GV can be measured using various parameters, but to date, a gold standard has not been identified. This underscores the need for further studies in this field also to identify the optimal treatment. CONCLUSIONS: We reviewed the definition of GV, the pathogenetic mechanisms of atherosclerosis, and its relationship with diabetic complications.

Association of blood pressure with incident diabetic microvascular complications among diabetic patients: Longitudinal findings from the UK Biobank.

Background: Evidence suggests a correlation of blood pressure (BP) level with presence of diabetic microvascular complications (DMCs), but the effect of BP on DMCs incidence is not well-established. We aimed to explore the associations between BP and DMCs (diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy) risk in participants with diabetes. Methods: This study included 23 030 participants, free of any DMCs at baseline, from the UK Biobank. We applied multivariable-adjusted Cox regression models to estimate BP-DMCs association and constructed BP genetic risk scores (GRSs) to test their association with DMCs phenotypes. Differences in incidences of DMCs were also compared between the 2017 ACC/AHA and JNC 7 guidelines (traditional criteria) of hypertension. Results: Compared to systolic blood pressure (SBP)<120 mm Hg, participants with SBP≥160 mm Hg had a hazard ratio (HR) of 1.50 (95% confidence interval (CI) = 1.09, 2.06) for DMCs. Similarly, DMCs risk increased by 9% for every 10 mm Hg of higher SBP at baseline (95% CI = 1.04, 1.13). The highest tercile SBP GRS was associated with 32% higher DMCs risk (95% CI = 1.11, 1.56) compared to the lowest tercile. We found no significant differences in DMCs incidence between JNC 7 and 2017 ACC/AHA guidelines. Conclusions: Genetic and epidemiological evidence suggests participants with higher SBP had an increased risk of DMCs, but hypertension defined by 2017 ACC/AHA guidelines may not impact DMCs incidence compared with JNC 7 criteria, contributing to the care and prevention of DMCs.

Epigenetic basis of diabetic vasculopathy.

Type 2 diabetes mellitus (T2DM) causes peripheral vascular disease because of which several blood-borne factors, including vital nutrients fail to reach the affected tissue. Tissue epigenome is sensitive to chronic hyperglycemia and is known to cause pathogenesis of micro- and macrovascular complications. These vascular complications of T2DM may perpetuate the onset of organ dysfunction. The burden of diabetes is primarily because of a wide range of complications of which nonhealing diabetic ulcers represent a major component. Thus, it is imperative that current research help recognize more effective methods for the diagnosis and management of early vascular injuries. This review addresses the significance of epigenetic processes such as DNA methylation and histone modifications in the evolution of macrovascular and microvascular complications of T2DM.

Relationship of advanced glycation end-products in hypertension in diabetic patients: a systematic review.

Diabetes mellitus and arterial hypertension are among the five risk factors that increase mortality in the world. Both are chronic, non-communicable diseases (NCDs), that have a pathophysiological association. Advanced glycation end products (AGEs), produced by the lack of glycemic control in diabetic patients, interact with their AGE receptors (AGER) resulting in increased arterial stiffness, inflammation and endothelial changes - which increases the risk of developing hypertension and other complications. We ran a systematic review in Pubmed, SciELO, Cochrane Library and Web of Science databases using keywords and Boolean operators to optimize the search, with the objective of assessing the mechanism of non-enzymatic glycation of proteins present in patients with diabetes and its correlation with the onset of hypertension, exposing all the endothelial and cellular damage caused by AGEs. We found 719 papers, of which 99 were read in full, and 26 met the eligibility criteria and were included in the present review. AGEs should be considered one of the main cardiometabolic risk factors. Reducing the AGE-AGER interaction will result in cardiovascular protection and increased life expectancy.

Fatty liver and atherogenic dyslipidemia have opposite effects on diabetic micro- and macrovascular disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver (FL) is comorbid with obesity, metabolic syndrome and type 2 diabetes. Atherogenic dyslipidaemia (AD), frequent in FL, is associated with risk of micro- and macrovascular complications. Given the paradoxical ocular protection of FL in T2DM, we studied how FL modulates micro- and macrovascular complications as a function of AD. METHODS: Cross-sectional factorial analysis of 744 diabetic patients in whom FL, identified by ultrasonography, was present in 68%. AD, defined by low HDL-C plus elevated TG, was present in 45%. Four groups were analysed as regards cardiometabolic features, micro-/macroangiopathies, cataract and ocular hypertonia: FL[-]AD[-] (n = 171); FL[-]AD[+] (n = 66); FL[+]AD[-] (n = 235); and FL[+]AD[+] (n = 272). RESULTS: Age, gender and glycemic control were similar across groups. Prevalence of overall macroangiopathy and coronary artery disease were higher in patients with AD, irrespective of FL. Overall macroangiopathy was higher, by 64% in FL[-]AD[+] and by 38% in FL[+]AD[+]. Coronary artery disease was higher, by 128%, in FL[-]AD[+], and by 67%, in FL[+]AD[+]. (Micro)albuminuria was more frequent (+55%) in FL[-] AD[+] compared to FL[-] AD[-]. Retinopathy prevalence was 35% in FL[-], unaffected by AD. Retinopathy frequency was much lower in FL[+], irrespective of AD, decreased by -47% in FL[+]AD[-] and -32% in FL[+]AD[+] (vs. FL[-]AD[-]). Ocular hypertonia was present in 13%, and its prevalence was also markedly lower (-31%) in FL[+]. Cataract frequency was 29%, also lesser in FL[+] (24% vs. 39%), irrespective of AD. CONCLUSIONS: Multi-level eye protection in diabetes is linked to non-alcoholic fatty liver independently of atherogenic dyslipidemia.

Diabetes Physical Examination.

The physical examination of the patient with diabetes may have revealed findings that confirm the diagnosis, classify the type of diabetes, and begin to evaluate for the macro- and microvascular complications of diabetes and significant comorbid conditions. While screening for the diagnosis of diabetes occurs with assessment for abnormal blood glucose, given the high rates of morbidity and mortality associated with diabetes, utilization of the physical examination plays a key role in identifying patients at risk for the complications of diabetes. The discussion of elements of the physical examination relevant to the patient with diabetes, both type 1 and type 2, will be discussed in this article.

What is the impact of microvascular complications of diabetes on severe COVID-19?

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.

Loss of independence as a metric for racial disparities in lower extremity amputation for diabetes: A National Surgery Quality Improvement Program (NSQIP) analysis.

INTRODUCTION: This study assessed the association between race/ethnicity and amputation with mortality and loss of independence (LOI) for diabetic gangrene. METHODS: We analyzed the American College of Surgeons National Surgery Quality Improvement Program database from 2016 to 2019. Chi-squared tests were performed to evaluate differences in baseline characteristics and complications. Multivariable logistic regression was performed to model LOI and 30-day mortality. RESULTS: 5250 patients with diabetes underwent lower extremity amputation as treatment for gangrene. Hispanic patients were more likely to undergo below the knee amputation (BKA) (P = 0.006). Guillotine amputation (GA) was associated with age > 65 (P < 0.0001), independent functional status prior to admission (P < 0.0001), and mortality (OR 1.989, 95%CI 1.29-3.065), but was not associated with LOI. Mortality was less frequent in Black patients (OR 0.432, 95%CI 0.207-0.902), but loss of independence (LOI) was more frequent in Black patients (OR 1.373, 95%CI 1.017-1.853). Hispanic patients were less likely to experience LOI (OR 0.575, 95%CI 0.477-0.693). CONCLUSIONS: LOI and mortality provide contrasting perspectives on outcomes following lower extremity amputation. Further assessment of risk factors may illuminate healthcare disparities.

Incidence rates and predictors of microvascular and macrovascular complications in patients with type 2 diabetes: Results from the longitudinal global discover study.

BACKGROUND: Micro- and macrovascular complications are a major cause of morbidity and mortality in people with type 2 diabetes (T2D). We sought to understand the global incidence rates and predictors of these complications. METHODS: We examined the incidence of vascular complications over 3 years of follow-up in the DISCOVER study-a global, observational study of people with T2D initiating second-line glucose-lowering therapy. Hierarchical Cox proportional hazards regression models examined factors associated with development of micro- and macrovascular complications during follow-up. RESULTS: Among 11,357 people with T2D from 33 countries (mean age 56.9 ± 11.7 years, T2D duration 5.7 ± 5.1 years, HbA1c 8.4 ± 1.7%), 19.0% had a microvascular complication at enrolment (most commonly neuropathy), and 13.2% had a macrovascular complication (most commonly coronary disease). Over 3 years of follow-up, 16.0% developed an incident microvascular complication, and 6.6% had an incident macrovascular complication. At the end of 3 years of follow-up, 31.5% of patients had at least one microvascular complication, and 16.6% had at least one macrovascular complication. Higher HbA1c and smoking were associated with greater risk of both incident micro- and macrovascular complications. Known macrovascular complications at baseline was the strongest predictor for development of new microvascular complications (HR 1.40, 95% CI 1.21 -1.61) and new macrovascular complications (HR 3.39, 95% CI 2.84 -4.06). CONCLUSIONS: In this global study, both the prevalence and 3-year incidence of vascular complications were high in patients with relatively short T2D duration, highlighting the need for early risk-factor modification.

Predictors of outcome in diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia.

OBJECTIVE: The incidence of chronic limb-threatening ischemia in diabetic patients is increasing. The factors influencing outcome after infrapopliteal revascularization in these patients are largely unknown. Therefore, this study aims to identify the impact of perioperative glucose control on the long-term outcomes in this patient cohort, and furthermore to identify other factors independently associated with outcome. METHODS: Consecutive diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia were identified. Patients' demographics, procedural details, daily capillary blood glucose, and hemoglobin A1C levels were collected and analyzed against the study end points using Kaplan-Meier and Cox regression analysis. RESULTS: A total of 437 infrapopliteal target vessels were successfully crossed in 203 patients. Amputation-free survival by Kaplan-Meier (estimate (standard error)%) was 74 (3.3)% and 63 (3.7)%, primary patency was 61 (4.2)% and 50 (4.9)%, assisted primary patency was 69 (5.2)% and 55 (6.1)%, and secondary patency was 71 (3.8)% and 59 (4.1)% at 1 year and 2 years, respectively. Cox regression analysis showed high perioperative capillary blood glucose levels to be an independent predictor of binary restenosis (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.31-1.1.78; P = .015). Postprocedural dual-antiplatelet therapy was found to be an independent predictor of amputation-free survival (HR, 1.69; 95% CI, 1.04-2.75; P = .033), and freedom from major adverse limb events (HR: 1.96; 95% CI, 1.16-3.27; P = .023) and baseline estimated glomerular filtration rate was significantly associated with better amputation-free survival (HR, 0.52; 95% CI, 0.31-0.87; P = .014). CONCLUSIONS: Poor perioperative glycemic control is associated with a higher incidence of restenosis after infrapopliteal revascularization in diabetic patients. Dual antiplatelet therapy is associated with better outcomes in this group.

Ankle-Brachial Index Is Independently Associated With Cardiovascular Outcomes and Foot Ulcers in Asian Patients With Type 2 Diabetes Mellitus.

Background and Aims: The ankle-brachial index (ABI) is an efficient tool for objectively documenting the presence of lower-extremity peripheral arterial disease (PAD). The predictive factors of cardiovascular events and diabetic foot ulcer were not clear from the ABI examination in Taiwanese patients with type 2 diabetes mellitus (DM). Methods: We enrolled 482 patients with type 2 DM who regularly visited the outpatient department of Chang Gung Memorial Hospital and received ABI as well as brachial-ankle pulse wave velocity (ba-PWV) examinations from 2010 to 2017. Age, gender, PAD symptoms, comorbidities, family history of chronic diseases, lifestyle (smoking, alcohol consumption, and exercise), height, weight, waist circumference, monofilament testing and foot ulcer status were studied. Results: There were 104 (22%) patients (mean age, 67.8 years) with the ABI <1.0. These patients with low ABI (ABI<1.0) had a significantly older age (p=0.001), higher delta PWV (p<0.001), higher rates of stroke (p=0.007), myocardial infarction (p=0.016), and foot ulcer (p=0.039). In a multivariable analysis model, the adjusted odds ratio (aOR) for myocardial infarction, stroke, and foot ulcers associated with low ABI were 1.219 (0.397-3.743, p=0.729), 1.204 (0.556-2.610, p=0.638), and 2.712 (1.199-6.133, p=0.017), respectively. The patients with low PWV (PWV<1400 cm/s) were significantly younger (p<0.001) and had a lower rate of hypertension (p<0.001), and higher percentages of stroke (p=0.027) and dialysis (p=0.041) family history. Conclusions: Low ABI was associated with cardiovascular events and diabetic foot ulcer independently in patients with type 2 DM.

Peripheral Artery Disease on The Prognosis Value of Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Retrospective, Single-Center Cohort Study.

OBJECTIVE: The purpose of this investigation aimed to clarify the impact of peripheral artery disease (PAD) on the prognosis value of patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). METHODS: The SPSS 16 software was used for secondary analysis of DRYAD database data. A total of 204 patients were enrolled from Shinonoi General Hospital for newly diagnosed stable CAD and received PCI performance between October 2014 and October 2017. Patients with old myocardial infarction (MI) were excluded. We divided patients into two groups with PAD and without PAD. The primary endpoints were major adverse cardiac events (MACE, defined as all-cause death, non-fatal MI, and non-fatal stroke) and cardiovascular events (defined as cardiovascular death, non-fatal MI, and non-fatal stroke). The secondary outcomes were the individual components of the composite primary outcomes. The median follow-up time was 783 days. RESULTS: No statistical difference was found between PAD and non-PAD patients of lesional characteristics. Spearman's rank correlations indicate diabetes mellitus (DM) (P = 0.019) and HbA1c (P = 0.009) are positively correlated with PAD. In Kaplan-Meier analysis, patients with PAD predicted poor prognosis in MACE (P < 0.05) and cardiovascular events (P < 0.05). In Multivariable Cox proportional hazards analysis, patients with PAD independently predicted MACE and cardiovascular events. CONCLUSIONS: PAD is a significant mediator for the prognosis of patients with stable CAD who underwent PCI treatment.

The Importance of Prognostic Nutritional Index in Predicting Acute Renal Failure After On-Pump Coronary Artery Bypass Operations in Patients with Insulin-Dependent Diabetes Mellitus.

BACKGROUND: After coronary artery bypass graft (CABG) operations, acute kidney injury (AKI) appears at 5-30% rates, and this rate increases even more in patients with diabetes mellitus (DM). Prognostic nutritional index (PNI) is known as a valuable parameter that affects cardiovascular surgery outcomes. In this current study, we aimed to investigate the importance of PNI value in predicting AKI after on-pump CABG operations in insulin-dependent diabetic patients. METHODS: A total of 254 consecutive patients with insulin- dependent diabetes who underwent on-pump CABG in our clinic between January 2016 and January 2020 retrospectively were included in this study. In the postoperative period, patients were registered as the renal failure group (Group 1), and those who did not develop renal failure were registered as Group 2. RESULTS: A total of 255 patients with DM were included in the study. There were 82 patients in Group 1 and 173 patients in Group 2. There was no difference between the groups, in terms of age, gender, smoking, and hyperlipidemia rates. Hypertension rate significantly was higher in Group 2 (P = .001). In multivariate logistic regression analysis, hypertension (OR: 1.226, 95% CI: 1.114-2.459, P = .026), need for inotropic support (OR: 1.128, 95% CI: 1.070-1.784, P = .033), increased blood product use (OR: 1.291, 95% CI: 1.112-2.156, P = .021) preoperative high creatinine (OR: 3.563, 95% CI: 2.497-5.559, P < .001), and PNI (OR: 1.327, 95% CI: 1.118-2.785, P = .012) were independent predictors of AKI. CONCLUSION: In our study, we determined PNI value as an independent predictor in predicting acute renal injury occurring after on-pump CABG operations in patients with insulin-dependent DM.

Effect of umbilical cord blood stem cell transplantation on restenosis after endovascular interventional therapy for diabetic hindlimb vascular disease.

This study aimed to investigate the mechanism of human umbilical cord blood stem cell (HUCBSC) transplantation on restenosis after percutaneous transluminal angioplasty (PTA) for diabetic hindlimb vascular disease in rabbits. After successfully preparing a rabbit model of diabetic hindlimb vascular disease, 16 rabbits were randomly assigned to two groups. Of these, 8 rabbits received PTA surgery alone (PTA group), and the other 8 rabbits received PTA and HUCBSC (PTA+HUCBSC group) treatments. Five more healthy rabbits were set as healthy control (HC group). Samples were collected after 4 weeks of treatment. The expressions of regulator of calcineurin 1 (RCAN1) and calcineurin A (CnA) in the diseased artery were detected by immunofluorescence staining. The distribution of HUCBSCs was observed by pathological examination in transplanted artery, distal artery, and liver. Cytology experiments were applied to assess the levels of JAK and STAT3, and the migration and proliferation of human aortic vascular smooth muscle cells (HA-VSMC). In the rabbit model of diabetic vascular lesions in the hindlimbs, we found the stenosis of the femoral artery became more and more serious with time, and the expression level of PCNA positive cells was also gradually increased. The expression levels of RCAN1 and CnA in the PTA+HUCBSC group were significantly lower than those in PTA group. HUCBSC inhibited the migration and proliferation of HA-VSMC via JAK/STAT3 pathway. After HUCBSC local transplantation, HUCBSC had no distal tissue distribution. HUCBSC transplantation may prevent restenosis after PTA of diabetic hindlimb vascular disease through JAK/STAT3 pathway.