scholarly journals Elevation in blood flow and shear rate prevents hyperglycemia-induced endothelial dysfunction in healthy subjects and those with type 2 diabetes

2015 ◽  
Vol 118 (5) ◽  
pp. 579-585 ◽  
Author(s):  
Arno Greyling ◽  
Tim H. A. Schreuder ◽  
Thijs Landman ◽  
Richard Draijer ◽  
Rebecca J. H. M. Verheggen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Flow ◽  
Shear Rate ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Interaction Effect ◽  
Healthy Subjects ◽  
Local Heating ◽  
Oral Glucose

Hyperglycemia, commonly present after a meal, causes transient impairment in endothelial function. We examined whether increases in blood flow (BF) protect against the hyperglycemia-mediated decrease in endothelial function in healthy subjects and patients with type 2 diabetes mellitus (T2DM). Ten healthy subjects and 10 age- and sex-matched patients with T2DM underwent simultaneous bilateral assessment of brachial artery endothelial function by means of flow-mediated dilation (FMD) using high-resolution echo-Doppler. FMD was examined before and 60, 120, and 150 min after a 75-g oral glucose challenge. We unilaterally manipulated BF by heating one arm between minute 30 and minute 60. Oral glucose administration caused a statistically significant, transient increase in blood glucose in both groups ( P < 0.001). Forearm skin temperature, brachial artery BF, and shear rate significantly increased in the heated arm ( P < 0.001), and to a greater extent compared with the nonheated arm in both groups (interaction effect P < 0.001). The glucose load caused a transient decrease in FMD% ( P < 0.05), whereas heating significantly prevented the decline (interaction effect P < 0.01). Also, when correcting for changes in diameter and shear rate, we found that the hyperglycemia-induced decrease in FMD can be prevented by local heating ( P < 0.05). These effects on FMD were observed in both groups. Our data indicate that nonmetabolically driven elevation in BF and shear rate can similarly prevent the hyperglycemia-induced decline in conduit artery endothelial function in healthy volunteers and in patients with type 2 diabetes. Additional research is warranted to confirm that other interventions that increase BF and shear rate equally protect the endothelium when challenged by hyperglycemia.

scholarly journals Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

2018 ◽  
Vol 315 (6) ◽  
pp. E1242-E1250 ◽  
Author(s):  
Donghua Hu ◽  
Ryan D. Russell ◽  
Devika Remash ◽  
Timothy Greenaway ◽  
Stephen Rattigan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Resistance Training ◽  
Blood Volume ◽  
Fasting Blood Glucose ◽  
Microvascular Blood Flow ◽  
Oral Glucose ◽  
Model Assessment

The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = −0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.

Vascular dysfunction and insulin stimulated blood flow : impact of physical inactivity and type 2 diabetes

2014 ◽  
Author(s):  
◽  
Leryn J. Boyle
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Flow ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Physical Inactivity ◽  
Vascular Dysfunction ◽  
Insulin Stimulation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Individuals with type 2 diabetes (T2D) have blunted femoral artery insulin mediated blood flow which is critical for the delivery and uptake of glucose into skeletal muscle. However, it is unclear in humans the precise mechanisms by which insulin resistance impairs insulin stimulated blood flow. Further, chronic physical inactivity is a powerful stimulus for reduced insulin sensitivity and vascular dysfunction; however, the effects of short term, modest reductions in physical activity are limited. Thus, we examined 1) if inactivity for 5 days would impair endothelial function in healthy individuals (study one) 2) if reducing whole body insulin sensitivity, via 5 days of inactivity, would impair the blood flow response to insulin stimulation in parallel with glycemic control (study two) and 3) phosphorylation of endothelial nitric oxide (eNOS) and endothelin-1 (ET-1) production to insulin stimulation would be decreased and increased, respectively, in insulin resistant individuals (study three). We demonstrated significant reductions in endothelial function with only 5 days of reduced daily steps while blood flow to glucose ingestion was unaltered. Further, in obese humans with type 2 diabetes it does not appear that that the reduction in blood flow to 1 hr of insulin stimulation is due to altered peNOS or ET-1. Collectively, these data suggest that reduced daily physical activity and chronic insulin resistance mediate negative impacts on vascular function and insulin stimulated blood flow and signaling.

scholarly journals Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

2019 ◽  
Vol 20 (15) ◽  
pp. 3775 ◽  
Author(s):  
Cesar A. Meza ◽  
Justin D. La Favor ◽  
Do-Houn Kim ◽  
Robert C. Hickner
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Enzymatic Production

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

Endothelial function of young healthy males following whole body resistance training

2005 ◽  
Vol 98 (6) ◽  
pp. 2185-2190 ◽  
Author(s):  
M. Rakobowchuk ◽  
C. L. McGowan ◽  
P. C. de Groot ◽  
J. W. Hartman ◽  
S. M. Phillips ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Rate ◽  
Resistance Training ◽  
Endothelial Function ◽  
Resistance Exercise ◽  
Brachial Artery ◽  
Whole Body ◽  
Flow Mediated Dilation ◽  
Body Resistance ◽  
Time Point

Given the increasing emphasis on performance of resistance exercise as an essential component of health, we evaluated, using a prospective longitudinal design, the potential for resistance training to affect arterial endothelial function. Twenty-eight men (23 ± 3.9 yr old; mean ± SE) engaged in 12 wk of whole body resistance training five times per week using a repeating split-body 3-day cycle. Brachial endothelial function was measured using occlusion cuff-induced flow-mediated dilation. After occlusion of the forearm for 4.5 min, brachial artery dilation and postocclusion blood flow was measured continuously for 15 and 70 s, respectively. Peak and 10-s postocclusion blood flow, shear rate, and brachial artery flow-mediated dilation (relative and normalized to shear rate) were measured pretraining (Pre), at 6 wk of training (Mid), and at 13 wk of training (Post). Results indicated an increase of mean brachial artery diameter by Mid and Post vs. Pre. Peak and 10-s postocclusion blood flow increased by Mid and remained elevated at Post; however, shear rates were not different at any time point. Relative and normalized flow-mediated dilation was also not different at any time point. This study is the first to show that peripheral arterial remodeling does occur with resistance training in healthy young men. In addition, the increase in postocclusion blood flow may indicate improved resistance vessel function. However, unlike studies involving endurance training, flow-mediated dilation did not increase with resistance training. Thus arterial adaptations with high-pressure loads, such as those experienced during resistance exercise, may be quite different compared with endurance training.

Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease

2004 ◽  
Vol 287 (6) ◽  
pp. E1209-E1215 ◽  
Author(s):  
Thomas Nyström ◽  
Mark K. Gutniak ◽  
Qimin Zhang ◽  
Fan Zhang ◽  
Jens Juul Holst ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Healthy Subjects ◽  
Stable Coronary Artery Disease ◽  
Artery Disease ◽  
Type 2 Diabetic ◽  
Diabetes Patients

GLP-1 stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying, and inhibits small bowel motility, all actions contributing to the anti-diabetogenic peptide effect. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease. Therefore, interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients. We investigated GLP-1's effect on endothelial function and insulin sensitivity (SI) in two groups: 1) 12 type 2 diabetes patients with stable coronary artery disease and 2) 10 healthy subjects with normal endothelial function and SI. Subjects underwent infusion of recombinant GLP-1 or saline in a random crossover study. Endothelial function was measured by postischemic FMD of brachial artery, using ultrasonography. SI [in (10−4 dl·kg−1·min−1)/(μU/ml)] was measured by hyperinsulinemic isoglycemic clamp technique. In type 2 diabetic subjects, GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(%) (3.1 ± 0.6 vs. 6.6 ± 1.0%, P < 0.05), with no significant effects on SI (4.5 ± 0.8 vs. 5.2 ± 0.9, P = NS). In healthy subjects, GLP-1 infusion affected neither FMD(%) (11.9 ± 0.9 vs. 10.3 ± 1.0%, P = NS) nor SI (14.8 ± 1.8 vs. 11.6 ± 2.0, P = NS). We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease. This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment.

scholarly journals Rivaroxaban compared with low-dose aspirin in individuals with type 2 diabetes and high cardiovascular risk: a randomised trial to assess effects on endothelial function, platelet activation and vascular biomarkers

Diabetologia ◽  
2021 ◽  
Author(s):  
Frank Pistrosch ◽  
Jan B. Matschke ◽  
Dorothea Schipp ◽  
Bernhard Schipp ◽  
Elena Henkel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Flow ◽  
Arterial Stiffness ◽  
Endothelial Function ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Subclinical Inflammation ◽  
Direct Factor

Abstract Aims/hypothesis Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation. Methods We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2–20 years), subclinical inflammation (high-sensitivity C-reactive protein 2–10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. Furthermore, we investigated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro. Results Rivaroxaban treatment for 20 weeks (n = 89) resulted in a significant improvement of post-ischaemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml, p = 0.004), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level vs aspirin. We did not find significant differences of arterial stiffness or further biomarkers. Neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets. The number of PMPs increased significantly with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl−1, p = 0.005) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl−1, p = 0.021). PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin. Rivaroxaban was associated with a higher number of bleeding events. Conclusions/interpretation Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding. Trial registration: ClinicalTrials.gov NCT02164578. Funding The study was supported by a research grant from Bayer Vital AG, Germany. Graphical abstract

scholarly journals Association of the polymorphism in the androgen receptor gene and endothelial function in men with type 2 diabetes

2015 ◽  
Vol 18 (4) ◽  
pp. 35-40 ◽  
Author(s):  
Irina Alekseevna Khripun ◽  
Sergey Vladislavovich Vorobyev ◽  
Michael Iosifovich Kogan
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Metabolism ◽  
Androgen Receptor ◽  
Endothelial Function ◽  
Flow Velocity ◽  
Brachial Artery ◽  
Cag Repeats ◽  
Atherogenic Index ◽  
Brachial Artery Diameter

In recent years, actively studied the effect of androgen deficiency on the cardiovascular system, including endothelial function. Genomic effects of testosterone caused by the length of CAG repeats polymorphism in the androgen receptor (AR) gene.Aim. To examine the association of the polymorphism in the AR gene and carbohydrate, lipid metabolism, endothelial function in men with type 2 diabetes.Materials and methods. We examined 88 men, aged 40-65 years (mean age 53±6,4years) with type 2 diabetes. All patients underwent the study of carbohydrate and lipid metabolism, the assessment of vasomotor endothelial function of the brachial artery by ultrasound sonography, were studied biochemical markers of endothelial dysfunction – ICAM-1, VCAM-1, p-selectin, e-selectin, resistin and number of CAG-repeats in the AR gene. Statistical analysis was performed using the application package SPSS 21,0 using regression analysis.Results. The number of CAG repeats had a significant positive regression to the level of total testosterone, a weak negative regression of the number of CAG repeats in the AR gene and lipid metabolism: triglycerides, LDL, atherogenic index. The assessment of the brachial artery ultrasonography revealed negative regression of the baseline brachial artery diameter and blood flow velocity in the endothelium-dependent vasodilation. The number of CAG repeats was significantly correlated with the levels of p-selectin and resistin. Thus, increasing the number of CAG repeats in the AR gene via a weakening of sensitivity to androgens leads to disruption of endothelial function in men with type 2 diabetes. Increasing the number of CAG repeats in the AR gene leads to deterioration of linear flow velocity during the test with reactive hyperemia with increasing production of p-selectin and resistin.Conclusions. The number of CAG repeats in the AR gene can be regarded as a predictor of the development and progression of cardiovascular lesions in men with type 2 diabetes.

scholarly journals Endothelial Function in Women with and without a History of Glucose Intolerance in Pregnancy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Shireen Brewster ◽  
John Floras ◽  
Bernard Zinman ◽  
Ravi Retnakaran
Keyword(s):  
Shear Rate ◽  
Endothelial Dysfunction ◽  
Glucose Tolerance ◽  
Endothelial Function ◽  
Glucose Intolerance ◽  
Brachial Artery ◽  
Reactive Hyperemia ◽  
Oral Glucose ◽  
Oral Glucose Tolerance Testing ◽  
In Pregnancy

Background/Aims. Gestational diabetes mellitus (GDM) and milder gestational impaired glucose tolerance (GIGT) identify women who are at risk of developing cardiovascular disease. Endothelial dysfunction, as indicated by impaired flow-mediated dilatation (FMD) on brachial artery ultrasound, is an early marker of vascular disease. Thus, we sought to evaluate endothelial function in women with and without recent glucose intolerance in pregnancy.Methods. One-hundred and seventeen women underwent oral glucose tolerance testing (OGTT) in pregnancy, enabling stratification into those with normal gestational glucose tolerance (n=59) and those with GDM or GIGT (n=58). 6 years postpartum, they underwent a repeat of OGTT and brachial artery FMD studies, enabling assessment of FMD and 4 secondary vascular measures: FMD after 60 seconds (FMD60), baseline arterial diameter, peak shear rate, and reactive hyperemia.Results. There were no differences between the normal gestational glucose tolerance and GDM/GIGT groups in FMD (mean 8.5 versus 9.3%,P=0.61), FMD60(4.1 versus 5.1%,P=0.33), baseline diameter (3.4 versus 3.4 mm,P=0.66), peak shear rate (262.6 versus 274.8 s−1,P=0.32), and reactive hyperemia (576.6 versus 496.7%,P=0.07). After covariate adjustment, there were still no differences between the groups.Conclusion. Despite their long-term cardiovascular risk, women with glucose intolerance in pregnancy do not display endothelial dysfunction 6 years postpartum.

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