Vascular Disease In Diabetic Patients Research Articles

Chronic SIRT1 supplementation in diabetic mice improves endothelial function by suppressing oxidative stress.

Enhancing SIRT1 activity exerts beneficial cardiovascular effects. In diabetes, plasma SIRT1 levels are reduced. We aimed to investigate the therapeutic potential of chronic recombinant murine SIRT1 (rmSIRT1) supplementation to alleviate endothelial and vascular dysfunction in diabetic mice (db/db). Left internal mammary arteries obtained from patients undergoing coronary artery bypass grafting with or without a diagnosis of diabetes were assayed for SIRT1 protein levels. Twelve-week-old male db/db mice and db/+ controls were treated with vehicle or rmSIRT1 intraperitoneally for 4 weeks, after which carotid artery pulse wave velocity (PWV) and energy expenditure/activity were assessed by ultrasound and metabolic cages, respectively. Aorta, carotid, and mesenteric arteries were isolated to determine endothelial and vascular function using the myograph system.Arteries obtained from diabetic patients had significantly lower levels of SIRT1 relative to non-diabetics. In line, aortic SIRT1 levels were reduced in db/db mice compared to db/+ mice, while rmSIRT1 supplementation restored SIRT1 levels. Mice receiving rmSIRT1 supplementation displayed increased physical activity and improved vascular compliance as reflected by reduced PWV and attenuated collagen deposition. Aorta of rmSIRT1-treated mice exhibited increased endothelial nitric oxide (eNOS) activity, while endothelium-dependent contractions of their carotid arteries were significantly decreased, with mesenteric resistance arteries showing preserved hyperpolarization. Ex vivo incubation with reactive oxygen species (ROS) scavenger Tiron and NADPH oxidase inhibitor apocynin revealed that rmSIRT1 leads to preserved vascular function by suppressing NADPH oxidase (NOX)-related ROS synthesis. Chronic rmSIRT1 treatment resulted in reduced expression of both NOX1 and NOX4, in line with a reduction in aortic protein carbonylation and plasma nitrotyrosine levels. In diabetic conditions, arterial SIRT1 levels are significantly reduced. Chronic rmSIRT1 supplementation improves endothelial function and vascular compliance by enhancing eNOS activity and suppressing NOX-related oxidative stress. Thus, SIRT1 supplementation may represent novel therapeutic strategy to prevent diabetic vascular disease.

Serum Pentosidine is Associated with Cardiac Dysfunction and Atherosclerosis in T2DM.

The purpose of this paper is to investigate the relationship between serum pentosidine levels and cardiac function and vascular disease in diabetic patients, and to provide a new reference indicator for the early detection of diabetic cardiovascular complications. This was a cross-sectional study. One hundred and twenty-two patients with type 2 diabetes were grouped by LVEF quartiles to compare the differences between their clinical data and serum pentosidine levels. Also, the correlation between serum pentosidine and clinical indicators was assessed. The effect of serum pentosidine on cardiac function and vascular stiffness was analyzed by multiple stepwise regression. Serum pentosidine levels were higher in patients with LVEF ≤57%. Serum pentosidine levels were positively correlated with waist-to-hip ratio, hemoglobin, AIP, baPWV, LVESD, and ARD, and negatively correlated with LVEF. Low serum pentosidine was associated with increased LVESD; high pentosidine was significantly associated with increased ARD, high AIP and high baPWV. The results suggest that serum pentosidine, a member of AGEs, may reflect cardiac remodeling and dysfunction as well as atherosclerosis.

Well-posedness of a mathematical model of diabetic atherosclerosis with advanced glycation end-products

Atherosclerosis is a leading cause of death worldwide; it emerges as a result of multiple dynamical cell processes, including hemodynamics, endothelial damage, innate immunity and sterol biochemistry. Making matters worse, nearly 463 million people have diabetes, which increases atherosclerosis-related inflammation, diabetic patients are twice as likely to have a heart attack or stroke. The pathophysiology of diabetic vascular disease is generally understood. Dyslipidemia with increased levels of atherogenic low-density lipoprotein, hyperglycemia, oxidative stress and increased inflammation are factors that increase the risk and accelerate development of atherosclerosis. In a recent paper, Xie [Well-posedness of a mathematical model of diabetic atherosclerosis. J Math Anal Appl. 2022;505(2):125606], we have developed a mathematical model that includes the effect of hyperglycemia and insulin resistance on plaque growth. In this paper, we propose a more comprehensive mathematical model for diabetic atherosclerosis which include more variables; in particular, it includes the variable for Advanced Glycation End-Products (AGEs) concentration. Hyperglycemia trigger vascular damage by forming AGEs, which are not easily metabolized and may accelerate the progression of vascular disease in diabetic patients. The model is given by a system of partial differential equations (PDEs) with a free boundary. We also establish the local existence and uniqueness of solution to the model. The methodology is to reduce the free boundary to a fixed boundary and the system of PDEs to an abstract evolution equation in Banach spaces, and apply the theory of analytic semigroup.

Subclinical Diabetic Peripheral Vascular Disease and Epidemiology Using Logistic Regression Mathematical Model and Medical Image Registration Algorithm.

The study aims to explore the effect of subclinical diabetic peripheral vascular disease and an epidemiological investigation of colour Doppler ultrasound images based on a logistic regression mathematical model and a medical image registration algorithm. Subclinical diabetes patients were selected as subjects, and after ultrasound colour Doppler ultrasonography of peripheral blood vessels, ultrasound images were taken. The experimental results show that the area under the curve (AUC) predicted by the model was 0.748, the sensitivity was 94.12%, and the specificity was 67.93%. All Δ were smaller than a single pixel. The detection rate of colour Doppler ultrasonography was 82.6%, which was significantly better than that of clinical examination (P < 0.01). The age, course of disease, SBP, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) of the peripheral vascular disease group were significantly different from those of the no peripheral vascular disease group (P < 0.05). The incidence of peripheral vascular diseases and nonperipheral vascular diseases in male patients was remarkably higher than that in female patients (P < 0.05). Moreover, with the increase of age, the incidence of peripheral vascular disease and nonperipheral vascular disease in diabetic patients showed a trend of gradual increase (P < 0.05). In summary, the mathematical model and registration method have high accuracy for medical image registration of patients with the diabetes epidemic. In addition, the age, course of disease, SBP, LDL-C, TG, and TC of diabetic patients were significantly different from those of normal people, which can provide a reference for the development of later diabetes epidemiology.

Novel engineered, membrane‐tethered VEGF‐A variants promote formation of filopodia, proliferation, survival, and cord or tube formation by endothelial cells via persistent VEGFR2/ERK signaling and activation of CDC42/ROCK pathways

Therapeutic angiogenesis would be clinically valuable in situations such as peripheral vascular disease in diabetic patients and tissue reperfusion following ischemia or injury, but approaches using traditional isoforms of vascular endothelial growth factor-A (VEGF) have had little success. The isoform VEGF165 is both soluble and matrix-associated, but can cause pathologic vascular changes. Freely diffusible VEGF121 is not associated with pathologic angiogenesis, but its failure to remain in the vicinity of the targeted area presents therapeutic challenges. In this study, we evaluate the cellular effects of engineered VEGF variants that tether extracellular VEGF121 to the cell membrane with the goal of activating VEGF receptor 2 (VEGFR2) in a sustained, autologous fashion in endothelial cells. When expressed by primary human retinal endothelial cells (hRECs), the engineered, membrane-tethered variants eVEGF-38 and eVEGF-53 provide a lasting VEGF signal that induces cell proliferation and survival, increases endothelial permeability, promotes the formation of a cord/tube network, and stimulates the formation of elongated filopodia on the endothelial cells. The engineered VEGF variants activate VEGFR2, MAPK/ERK, and the Rho GTPase mediators CDC42 and ROCK, activities that are required for the formation of the elongated filopodia. The sustained, pro-angiogenic activities induced by eVEGF-38 and eVEGF-53support the potential of engineered VEGF variants-overexpressing endothelial cells as a novel combination of gene and cell-based therapeutic strategy for stimulating endothelial cell-autologous therapeutic angiogenesis.

Assessment of plasma level of cyclophilin A in type 2 diabetic patients suffering from vascular diseases

Background Peptidyl-prolyl isomerase cyclophilin A (CypA) plays important roles in inflammation. However, little is known about the mechanisms by which CypA exerts its effects. It is secreted in human by monocytes activated by high glucose level. It has a role as an inflammatory mediator in vascular tissue damage. Aim This study aims to compare plasma levels of CypA in type 2 diabetic patients with or without coronary artery disease (CAD) with those in healthy participants to determine the potential role of CypA in promoting vascular disease in diabetic patient and to study the association of high-sensitivity C-reactive protein with CypA levels. Patients and methods The present study was conducted on 80 participants who were divided into four groups: group 1, which included apparently healthy individuals; group 2, which included patients with type 2 diabetes mellitus (DM) without CAD; group 3, which included patients with type 2 DM with CAD; and group 4, which included patients with CAD without DM. The plasma level of CypA was measured using a CypA enzyme-linked immunosorbent assay kit. Results The results showed an increase in the median CypA concentration in all patient groups in comparison with the controls ( P P P Conclusion This study demonstrated that CypA has a potential role in promoting vascular disease in diabetic patients and revealed that CypA is a good biomarker for CAD with or without DM better than high-sensitivity C-reactive protein.

Serum markers for early detection of peripheral vascular disease in diabetic patients

Serum markers for early detection of peripheral vascular disease in diabetic patients

Monocyte-Derived Procoagulant Microvesicles Induced by High Glucose Can Be Attenuated by the Antioxidant N-Acetyl-L-Cysteine, Partly Through the P38/MAPK Pathway.

Microvesicles (MVs) are small membrane vesicles that are derived from many different cell types by a process of exocytic budding of the plasma membrane. MVs may be associated with a higher incidence of vascular disease in diabetic patients, but the mechanism of this association is unclear. Diabetic patients also show hypercoagulability and platelet hyperaggregability. In this study, we investigated the generation and activity of high glucose (HG)-induced MVs from monocytes to elucidate the potential mechanism of such MVs in diabetes. HG-induced MV generation from THP-1 monocytes before and after N-acetyl-L-cysteine (NAC) treatment was examined by enzyme-linked immunosorbent assay. MV activity was measured by spectrophotometry. Apoptosis and generation of reactive oxidative species (ROS) from THP-1 cells were detected by flow cytometry. Extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and P38/MAPK pathway components were also analyzed in treated monocytes. MVs were generated from THP-1 cells after 20 hr of exposure to HG (4.6-fold higher than untreated control cells), which was concomitant with a 3.3-fold increase in apoptosis (P < 0.01). The procoagulant activity (PCA) of the generated MVs was increased significantly by 4.1-fold (P < 0.01) relative to untreated cells. ROS levels peaked 2 hr after HG exposure. The frequency of MVs was greatly decreased after NAC treatment (P < 0.01). Both the ERK/MAPK and P38/MAPK pathway were activated after HG stimulation, whereas treatment with a P38 inhibitor decreased MV generation by 66% compared to untreated control. The generation of monocyte-derived MVs induced by HG was associated with PCA, concomitant with apoptosis and ROS generation. The P38/MAPK pathway was partly involved in this process as evidenced by the reduction in MV generation following treatment with a P38 inhibitor. Our results could provide insights into novel mechanisms of thrombogenicity in an HG state.

High density lipoprotein modulates osteocalcin expression in circulating monocytes: a potential protective mechanism for cardiovascular disease in type 1 diabetes

BackgroundCardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes (T1D). A pro-calcific drift of circulating monocytes has been linked to vascular calcification and is marked by the surface expression of osteocalcin (OCN). We studied OCN+ monocytes in a unique population with ≥50 years of T1D, the 50-Year Joslin Medalists (J50M).MethodsCD45 bright/CD14+/OCN+ cells in the circulating mononuclear blood cell fraction were quantified by flow cytometry and reported as percentage of CD45 bright cells. Mechanisms were studied by inducing OCN expression in human monocytes in vitro.ResultsSubjects without history of CVD (n = 16) showed lower levels of OCN+ monocytes than subjects with CVD (n = 14) (13.1 ± 8.4% vs 19.9 ± 6.4%, p = 0.02). OCN+ monocytes level was inversely related to total high density lipoprotein (HDL) cholesterol levels (r = −0.424, p = 0.02), large (r = −0.413, p = 0.02) and intermediate (r = −0.445, p = 0.01) HDL sub-fractions, but not to small HDL. In vitro, incubation with OxLDL significantly increased the number of OCN+ monocytes (p < 0.01). This action of OxLDL was significantly reduced by the addition of HDL in a concentration dependent manner (p < 0.001). Inhibition of the scavenger receptor B1 reduced the effects of both OxLDL and HDL (p < 0.05).ConclusionsLow OCN+ monocytes levels are associated with lack of CVD in people with long duration T1D. A possible mechanism for the increased OCN+ monocytes could be the elevated levels of oxidized lipids due to diabetes which may be inhibited by HDL. These findings suggest that circulating OCN+ monocytes could be a marker for vascular disease in diabetic patients and possibly modified by HDL elevation.

Berberine reduced blood pressure and improved vasodilation in diabetic rats.

Hyperglycemia and hypertension are considered to be the two leading risk factors for vascular disease in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and hypertension at the same time in diabetes. The objectives of this study are to investigate whether berberine treatment could directly reduce blood pressure and identify the molecular mechanism underlying the vascular protection of berberine in diabetic rats. Berberine was intragastrically administered with different dosages of 50, 100 and 200 mg/kg/day to diabetic rats for 8 weeks since the injection of streptozotocin. The endothelium-dependent/-independent relaxation in middle cerebral arteries was investigated. The activity of large-conductance Ca2+-activated K+ channel (BKCa) was investigated by recording whole-cell currents, analyzing single-channel activities and assessing the expressions of α- and β1-subunit at protein or mRNA levels. Results of the study suggest that chronic administration of 100 mg/kg/day berberine not only lowered blood glucose but also reduced blood pressure and improved vasodilation in diabetic rats. Furthermore, berberine markedly increased the function and expression of BKCa β1-subunit in cerebral vascular smooth muscle cells (VSMCs) isolated from diabetic rats or when exposed to hyperglycemia condition. The present study provided initial evidences that berberine reduced blood pressure and improved vasodilation in diabetic rats by activation of BKCa channel in VSMCs, which suggested that berberine might provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetes. Furthermore, our work indicated that activation of BKCa channel might be the underlying mechanism responsible for the vascular protection of berberine in diabetes.

Detection of Peripheral Arterial Disease Within the Foot Using Vascular Optical Tomographic Imaging: A Clinical Pilot Study

Vascular optical tomographic imaging (VOTI) is a novel imaging modality that is capable of detecting hemoglobin concentrations in tissue. VOTI is non-invasive, non-ionizing and does not require contrast injection. This technology was applied to the diagnosis of peripheral arterial disease (PAD) within lower extremities of diabetic patients with calcified arteries. This could be of substantial benefit as these patients suffer from comorbidities such as arterial incompressibility, which complicates diagnosis and monitoring. Forty individuals (10 non-diabetic patients with PAD, 10 diabetic patients with PAD, and 20 healthy volunteers) were enrolled in a diagnostic pilot study using the VOTI system. The patients were imaged during at high pressure cuff occlusion. The VOTI system was capable of quantifying the blood volume changes within the foot during the thigh cuff occlusion and outputting diagnostic parameters, such as change in hemoglobin concentration, enabling the assessment of foot perfusion. This study resulted in a statistically significant difference between the healthy cohort and both the non-diabetic and the diabetic PAD cohorts (p = .006, p = .006). Receiver operating characteristic (ROC) curve analysis showed that PAD diagnosis could be made with over 80% sensitivity or specificity depending on the characteristic cutoff point. In addition, VOTI was capable of providing the locations of under-perfused regions within the foot and evaluating the severity of arterial disease, even within diabetic patients with calcified arteries, who are traditionally difficult to diagnose. VOTI can effectively diagnose PAD independently of arterial compressibility, making it very useful for assessing vascular disease in diabetic patients.

The role of LDL-apheresis in the treatment of ulcers due to peripheral vascular disease in diabetic patients: a case report

The role of LDL-apheresis in the treatment of ulcers due to peripheral vascular disease in diabetic patients: a case report

Does adiponectin level explain the atherogenic properties of Hp 2-2 phenotype in type 2 diabetic patients?

ObjectivesHaptoglobin (Hb) and adiponectin are antioxidant proteins and independent predictors of atherosclerotic vascular disease in diabetic patients. The link between Hp phenotype and circulating adiponectin levels were examined. MethodsDiabetic patients were divided into two groups by Hp phenotype: Hp 2-2 group and non-Hp 2–2 group (Hp 2-1 and Hp 1-1). Blood glucose, HbA1C, insulin, lipids, CRP, HOMA-IR, 25OH vitamin D, leptin and adiponectin levels were measured. Pulse wave velocity (PWV) was performed using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). ResultsPWV was significantly higher in patients homozygous for the 2 allele (Hp 2-2) compared to non-Hp 2–2 patients (Hp 1-1 and Hp 1-2), p < 0.0001. Adiponectin was significantly lower in Hp 2-2 patients than in non-Hp 2–2 group (p < 0.016). Neither leptin nor the leptin adiponectin ratio (LAR) differed significantly between groups. ConclusionsPWV was significantly higher and plasma adiponectin levels were significantly lower in diabetic patients homozygous for the 2 allele (Hp 2-2). These differences were detected despite the lack of by-phenotype differences in glycemic control, blood pressure level or presence of cardiovascular risk factor and suggest an active role of adiponectin in the pathophysiology of vascular disease in this population.

P 1: Do adiponectin levels explain the atherogenic properties of Hp 2-2 phenotype in type 2 diabetic patients?

Haptoglobin (Hb) and adiponectin are antioxidant proteins and independent predictors of atherosclerotic vascular disease in diabetic patients. The link between Hp phenotype and circulating adiponectin levels were examined. Diabetic patients were divided into two groups by Hp phenotype: Hp 2-2 group and non-Hp 2-2 group (Hp2-1 and Hp 1–1). Blood glucose, HbA1C, insulin, lipids, CRP, HOMA-IR, 25OH vitamin D, leptin and adiponectin levels were measured. Pulse wave velocity (PWV) was performed using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). PWV was significantly higher in patients homozygous for the 2 allele (Hp 2-2) compared to non-Hp 2–2 patients (Hp 1-1 and Hp 1–2), p<0.0001. Adiponectin was significantly lower in Hp2-2 patients than in non-Hp 2-2 group (p<0.016). Neither leptin nor the leptin adiponectin ratio (LAR) differed significantly between groups. PWV was significantly higher and plasma adiponectin levels were significantly lower in diabetic patients homozygous for the 2 allele (Hp 2-2). These differences were detected despite the lack of by-phenotype differences in glycemic control, blood pressure level or presence of cardiovascular risk factor and suggest an active role of adiponectin in the pathophysiology of vascular disease in this patients population.

Lipoprotein(a), type 2 diabetes and nephropathy; the mystery continues

Lipoprotein(a), type 2 diabetes and nephropathy; the mystery continues

A grand challenge about multiple metabolic control: health care delivery from tertiary level hospital to primary care health center

Because of the economic growth and changes in lifestyle, diabetes has become a major public health problem in China. A national study from 2007 to 2008 showed that the age-standardized prevalences of diabetes and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes and 148.2 million adults with prediabetes. Data from Shanghai urban communities surveys indicated that the 3-year cumulative incidence rates of diabetes and pre-diabetes were nearly 5% and 11%, respectively. In diabetic patients, the prevalence of diabetic retinopathy was 16.9%. One of five known diabetic (KDM) patients and one of ten newly diagnosed diabetic patients had diabetic retinopathy. Even in the prediabetic group, the prevalence was over 5%. Among diabetes and prediabetes, the prevalence of albuminuria was 25.7% and 12.7%, respectively. The prevalence of peripheral vascular disease in diabetic patients was nearly 15%, much higher than that in prediabetes. Type 2 diabetes and its complications are imposing heavy economic burdens on individuals, families, health systems and countries including China. Since 2003, with the support of Department of Disease Control of Chinese Ministry of Health, Chinese Diabetes Society of the Chinese Medical Association published the Guideline for Diabetes Prevention and Treatment in Chinese. The guideline has been revised twice according to the evidence-based clinical trials. So far, multiple metabolic disorders control of diabetic patients is a global problem. Recently, we developed a Hospital-Community Diabetes Integrated Management to increase “three rates”, which were control rate, screening rate of chronic complication and awareness rate of diabetes knowledge in Shanghai communities. We established collaboration between urban hospitals (Tertiary hospitals) and community health services. The hospital and community health services center have their own responsibilities. Tertiary hospital was in charge of training, establishing management guideline and providing referral platform. The community health services center was in charge of organizing management team and medical record, implementing the management according to the guideline and starting dual referral. Up till now nearly 9,000 high risk individuals completed diabetes screening in 3 communities. And more than 5,000 and medical records were managed by the community health services. The “three rates” improved significantly as consequence.

Hypoglycaemia is more frequent in type 2 diabetic patients with co-morbid vascular disease: an analysis of the DiaRegis registry

Patients with type-2 diabetes are at risk for treatment- and disease-related complications. Little is known about the interrelation of hypoglycaemia and co-morbid vascular disease (VD), defined as coronary heart disease, stroke and peripheral arterial disease. Hypoglycaemia is associated with co-morbid VD in diabetic patients. DiaRegis is a prospective registry that included patients with type-2 diabetes in 2009/2010. Metric variables are displayed as median and quartiles. For the comparison of patients with or without VD Odds Ratios (OR) were determined from univariate analyses and adjusted for differences in patient characteristics (multivariable analysis). Data on hypoglycaemia and VD within the last 12 months were available for 3741 patients (98.2%) with a median (IQR) age of 65.9 (57.6-72.9) years; 46.7% were female. VD patients (n = 909; 24.3%) were older (70.7 vs 63.9 years; p < 0.0001), less often female (33.6% vs 50.9%; p < 0.0001) and had had diabetes for a longer duration (6.4 vs 5.4 years; p < 0.0001). Mean cholesterol (total, HDL and LDL) was also slightly lower (p < 0.0001). Glycaemic control (HbA1c, fasting and postprandial glucose) was comparable. VD patients received less metformin (80.7 vs 85.2%; p < 0.01) and more sulfonylureas (31.8 vs 27.6%; p < 0.05). There was an increased incidence of symptomatic hypoglycaemia with or without requiring help and with a need for medical assistance. After adjusting a number of baseline variables the rates of symptomatic hypoglycaemias with help remained significantly increased (OR 3.73 (95% CI 1.31-10.65) in patients with VD. As hypothesized there is a strong association between the incidence of hypoglycaemia and vascular disease at comparable glycaemic control, which confirms prior randomized controlled trial data suggesting an interrelationship between hypoglycaemia and vascular disease.

Lower Limb Vascular Disease in Diabetic Patients:: A Study with Calf Compression Contrast-enhanced Magnetic Resonance Angiography at 3.0 Tesla

To retrospectively analyze the significance of 3.0-T contrast-enhanced (CE) magnetic resonance angiography (MRA) with calf compression in the lower limbs of diabetic patients with peripheral vascular disease. Sixty-one type 2 diabetes patients underwent both MRA and digital subtraction angiography (DSA) within 1 week. The patients were divided into two groups: one with (pressure) and one without (conventional) calf compression during MRA. Two radiologists evaluated the quality of MRA images and compared the two groups. Cohen's kappa statistic was used to determine the concordance between MRA and DSA. Image quality in the calf and foot was better in the group with calf pressure than the conventional group without applied pressure (P = .001 [calf], 0.008 [foot]). Significantly more runoff vessels in the calf were detected with MRA than with DSA (P = .0043 [conventional], 0.0031 [pressure]). The kappa values were 0.928 in the conventional group and 0.979 in the pressure group, but in the conventional group, the diagnostic accuracy of CE-MRA was lower than that of DSA (P = .002). Diagnostic accuracy in the pressure group was significantly higher than that in the conventional group (P = .009). The overall sensitivity and specificity for >50% stenosis or occlusion was 93.8% and 98.5%, respectively, in the conventional group and 98.7% and 99.6%, respectively, in the pressure group. With calf compression, venous overlap (P = .0396, .0425) and deep vein overlap (P = .022, .022) were significantly reduced in the leg and foot. Calf compression with 3.0-T CE-MRA was convenient and practical and could improve image quality and diagnostic accuracy in diabetic patients with peripheral vascular disease by reducing venous overlap.

Impaired endothelial antithrombotic activity following short-term interruption of continuous subcutaneous insulin infusion in type1 diabetic patients

Review of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia. However, the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear. It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion (CSII) in type I diabetic patients. Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest. Blood glucose, insulin and 3-hydroxybutirate were measured to verify the metabolic response. A vein-occlusive (VO) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest. Coagulation factor VII and VIII were evaluated by one-stage PT and PTT method, respectively. TF, vWF, tPA and PAI-1 antigens were determined by ELISA, whereas tPA and PAI-1 activities using chromogenic methods. Plasma malondialdehyde (MDA) and protein carbonyl groups (PCG) levels were determined by HPLC and spectrophotometry, respectively. After the insulin deprivation phase, post-VO tPA antigen level significantly decreased (P = 0.0391), whereas TF and post-VO PAI-1 activity and antigen levels significantly increased (P = 0.0156 and P = 0.0234, respectively). Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values, respectively. In conclusion, the impairment of the fibrinolytic potential and the increases in TF, MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis. Thus, early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events.

Differential inhibition by hyperglycaemia of shear stress‐ but not acetylcholine‐mediated dilatation in the iliac artery of the anaesthetized pig

Clinical hyperglycaemia affects vascular endothelial function, but the effect on shear stress-induced arterial dilatation has not yet been established. We hypothesized that hyperglycaemia would inhibit this response via impaired glycocalyx mechanotransduction. Experiments were carried out in the anaesthetized pig in which pressure, blood flow and diameter of the left iliac artery were measured at two sites: proximal (d1) and distal (d2). Infusion of glucose, sufficient to raise blood glucose to 16-30 mm along the whole length of the artery, attenuated the shear stress-dependent dilatation in both sections of the artery with preservation of the responses to acetylcholine. The distal site was then isolated using snares and the lumen exposed to blood containing 25-35 mm glucose for 20 min. In the control situation, after exposure of both sections to normoglycaemia (5.7 mm glucose), both sections of artery showed increases in diameter in response to shear stress and acetylcholine. Hyperglycaemia attenuated the shear stress-dependent dilatation in the distal section only (P < 0.25), but not the response to acetylcholine. It is concluded from these results that the hyperglycaemia-impaired dilatation is consistent with loss of mechanotransducing properties of the endothelial glycocalyx by hyperglycaemia. These findings offer a possible explanation for the increased incidence of vascular disease in diabetic patients.