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The Acute Effects of Prolonged Uninterrupted Sitting on Vascular Function: A Systematic Review and Meta-analysis.
Taylor, FC, Pinto, AJ, Maniar, N, Dunstan, DW, Green, DJ
Medicine and science in sports and exercise. 2022;(1):67-76
Abstract
OBJECTIVE This study aimed to determine the dose-response relationship between prolonged sitting and vascular function in healthy individuals and those with metabolic disturbances and to investigate the acute effects, on vascular function, of interventions that target interrupting prolonged sitting. DESIGN This is a systematic review with meta-analysis. DATA SOURCES Ovid Embase, Ovid Medline, PubMed, and CINAHL were searched from inception to 4 December 2020. ELIGIBILITY CRITERIA Randomized crossover trials, quasi-randomized trials, and parallel group trials where vascular function (flow-mediated dilation [FMD]) was assessed before and after an acute period of sedentary behavior was used in this study. RESULTS Prolonged sitting resulted in a significant decrease in the standardized mean change (SMC) for lower-limb FMD at the 120-min (SMC = -0.85, 95% confidence interval [CI] = -1.32 to -0.38) and 180-min (SMC = -1.18, 95% CI = -1.69 to -0.66) time points. A similar pattern was observed for lower-limb shear rate. No significant changes were observed for any outcomes in the upper limb. Subgroup analysis indicated that prolonged sitting decreased lower-limb FMD in healthy adults (SMC = -1.33, 95% CI = -1.89 to -0.78) who had higher a priori vascular endothelial function, but not in those with metabolic and vascular dysfunction (SMC = -0.51, 95% CI = -1.18 to 0.15). Interrupting sitting with active interruptions increased the standardized mean difference for FMD, relative to prolonged sitting, but it was not statistically significant (0.13, 95% CI = -0.20 to 0.45). CONCLUSIONS Lower-limb vascular function is progressively impaired as a consequence of prolonged sitting, up to 180 min. A similar trend was not observed in upper-limb vascular function. Subgroup analysis indicated that prolonged sitting negatively affects healthy populations, a finding not observed in those with metabolic disturbances. Regularly interrupting sitting with activity may be beneficial for those with metabolic disturbances.
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Dapagliflozin effect on endothelial dysfunction in diabetic patients with atherosclerotic disease: a randomized active-controlled trial.
Sposito, AC, Breder, I, Soares, AAS, Kimura-Medorima, ST, Munhoz, DB, Cintra, RMR, Bonilha, I, Oliveira, DC, Breder, JC, Cavalcante, P, et al
Cardiovascular diabetology. 2021;(1):74
Abstract
BACKGROUND The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. METHODS In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). RESULTS Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. CONCLUSIONS Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.
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Effects of indulgent food snacking, with and without exercise training, on body weight, fat mass, and cardiometabolic risk markers in overweight and obese men.
Tucker, WJ, Jarrett, CL, D'Lugos, AC, Angadi, SS, Gaesser, GA
Physiological reports. 2021;(22):e15118
Abstract
We hypothesized that exercise training would prevent gains in body weight and body fat, and worsening of cardiometabolic risk markers, during a 4-week period of indulgent food snacking in overweight/obese men. Twenty-eight physically inactive men (ages 19-47 yr) with body mass index (BMI) ≥25 kg/m2 consumed 48 donuts (2/day, 6 days/week; ~14,500 kcal total) for 4 weeks while maintaining habitual diet. Men were randomly assigned to control (n = 9), moderate-intensity continuous training (MICT; n = 9), or high-intensity interval training (HIIT; n = 10). Exercise training occurred 4 days/week, ~250 kcal/session. Controls did not increase body weight, body fat, or visceral abdominal fat. This was partially explained by a decrease in self-reported habitual energy (-239 kcal/day, p = 0.05) and carbohydrate (-47 g/day; p = 0.02) intake. Large inter-individual variability in changes in body weight, fat, and fat-free mass was evident in all groups. Fasting blood pressure, and blood concentrations of glucose, insulin, and lipids were unchanged in all groups. Glucose incremental area under the curve during an oral glucose tolerance test was reduced by 25.6% in control (p = 0.001) and 32.8% in MICT (p = 0.01) groups. Flow-mediated dilation (FMD) was not changed in any group. VO2max increased (p ≤ 0.001) in MICT (9.2%) and HIIT (12.1%) groups. We conclude that in physically inactive men with BMI ≥25 kg/m2 , consuming ~14,500 kcal as donuts over 4 weeks did not adversely affect body weight and body fat, or several markers of cardiometabolic risk. Consumption of the donuts may have prevented the expected improvement in FMD with HIIT.
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Reference Intervals for Brachial Artery Flow-Mediated Dilation and the Relation With Cardiovascular Risk Factors.
Holder, SM, Bruno, RM, Shkredova, DA, Dawson, EA, Jones, H, Hopkins, ND, Hopman, MTE, Bailey, TG, Coombes, JS, Askew, CD, et al
Hypertension (Dallas, Tex. : 1979). 2021;(5):1469-1480
Abstract
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Circulating biomarkers of nitric oxide bioactivity and impaired muscle vasoreactivity to exercise in adults with uncomplicated type 1 diabetes.
Lespagnol, E, Tagougui, S, Fernandez, BO, Zerimech, F, Matran, R, Maboudou, P, Berthoin, S, Descat, A, Kim, I, Pawlak-Chaouch, M, et al
Diabetologia. 2021;(2):325-338
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Abstract
AIMS/HYPOTHESIS Early compromised endothelial function challenges the ability of individuals with type 1 diabetes to perform normal physical exercise. The exact mechanisms underlying this vascular limitation remain unknown, but may involve either formation or metabolism of nitric oxide (NO), a major vasodilator, whose activity is known to be compromised by oxidative stress. METHODS Muscle microvascular reactivity (near-infrared spectroscopy) to an incremental exhaustive bout of exercise was assessed in 22 adults with uncomplicated type 1 diabetes (HbA1c 64.5 ± 15.7 mmol/mol; 8.0 ± 1.4%) and in 21 healthy individuals (18-40 years of age). NO-related substrates/metabolites were also measured in the blood along with other vasoactive compounds and oxidative stress markers; measurements were taken at rest, at peak exercise and after 15 min of recovery. Demographic characteristics, body composition, smoking status and diet were comparable in both groups. RESULTS Maximal oxygen uptake was impaired in individuals with type 1 diabetes compared with in healthy participants (35.6 ± 7.7 vs 39.6 ± 6.8 ml min-1 kg-1, p < 0.01) despite comparable levels of habitual physical activity (moderate to vigorous physical activity by accelerometery, 234.9 ± 160.0 vs 280.1 ± 114.9 min/week). Compared with non-diabetic participants, individuals with type 1 diabetes also displayed a blunted exercise-induced vasoreactivity (muscle blood volume at peak exercise as reflected by ∆ total haemoglobin, 2.03 ± 5.82 vs 5.33 ± 5.54 μmol/l; interaction 'exercise' × 'group', p < 0.05); this was accompanied by lower K+ concentration (p < 0.05), reduced plasma L-arginine (p < 0.05)-in particular when HbA1c was high (mean estimation: -4.0, p < 0.05)-and lower plasma urate levels (p < 0.01). Nonetheless, exhaustive exercise did not worsen lipid peroxidation or other oxidative stress biomarkers, and erythrocytic enzymatic antioxidant resources were mobilised to a comparable extent in both groups. Nitrite and total nitrosation products, which are potential alternative NO sources, were similarly unaltered. Graphical abstract CONCLUSIONS/INTERPRETATION Participants with uncomplicated type 1 diabetes displayed reduced availability of L-arginine, the essential substrate for enzymatic nitric oxide synthesis, as well as lower levels of the major plasma antioxidant, urate. Lower urate levels may reflect a defect in the activity of xanthine oxidase, an enzyme capable of producing NO from nitrite under hypoxic conditions. Thus, both canonical and non-canonical NO production may be reduced. However, neither of these changes exacerbated exercise-induced oxidative stress. TRIAL REGISTRATION clinicaltrials.gov NCT02051504.
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Effects of tree nut and groundnut consumption compared with those of l-arginine supplementation on fasting and postprandial flow-mediated vasodilation: Meta-analysis of human randomized controlled trials.
Smeets, ETHC, Mensink, RP, Joris, PJ
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1699-1710
Abstract
INTRODUCTION l-arginine supplementation may improve vascular endothelial function. As tree nuts and groundnuts are a source of the amino acid l-arginine, we performed a meta-analysis of human randomized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of l-arginine supplementation on fasting and postprandial endothelial function as assessed by flow-mediated vasodilation of the brachial artery (FMD). METHODS Summary estimates of weighted mean differences (WMDs) in FMD and 95% confidence intervals (CIs) were calculated using random-effect meta-analyses. RESULTS A total of thirteen RCTs focusing on tree nut and groundnut consumption and nineteen RCTs investigating effects of l-arginine supplementation were included. Longer-term consumption of tree nuts and groundnuts increased fasting FMD by 1.09 %-point (PP) (95% CI: 0.49, 1.69, P < 0.001; I2: 76.7%, P < 0.001), while l-arginine supplementation (daily range: 3-21 g) increased fasting FMD by 0.53 PP (95% CI: 0.12, 0.93; P = 0.012; I2: 91.6%, P < 0.001). Effects between treatments were not statistically different (P = 0.31). Tree nut and groundnut consumption did not affect postprandial FMD responses (1.25 PP, 95% CI: -0.31, 2.81, P = 0.12; I2: 91.4%, P < 0.001), whereas l-arginine supplementation (range: 3-15 g) improved FMD during the postprandial phase by 2.02 PP (95% CI: 0.92, 3.13, P < 0.001; I2: 99.1%, P < 0.001). However, treatment effects did not differ significantly (P = 0.60). Overall, these results derive from high-quality evidence. CONCLUSION Longer-term consumption of tree nuts and groundnuts, as well as l-arginine supplementation did improve fasting endothelial function, as assessed by FMD. However, the positive effects of tree nuts and groundnuts could not be fully explained by the amount of l-arginine in these nuts. Only l-arginine supplementation did improve postprandial FMD, but effects were not different from those of tree nuts and groundnuts. Future studies should focus on the identifications of the bioactive nutrients in tree nuts and groundnuts and mechanistic pathways behind differences in postprandial and longer-term fasting changes in FMD.
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Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: a randomized trial.
Tuttolomondo, A, Cirrincione, A, Casuccio, A, Del Cuore, A, Daidone, M, Di Chiara, T, Di Raimondo, D, Corte, VD, Maida, C, Simonetta, I, et al
Cardiovascular diabetology. 2021;(1):1
Abstract
BACKGROUND Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage. AIMS We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditional antidiabetic treatment compared with traditional antidiabetic treatment alone in subjects with type 2 diabetes. METHODS Men and women (aged ≥ 50 years) with established or newly detected type 2 diabetes whose HbA1c level was 9.5% or less on stable doses of up to two oral glucose- lowering drugs with or without basal insulin therapy were eligible for randomization. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness (PWV: pulse wave velocity and augmentation index) and endothelial function (RHI: reactive hyperaemia index) were evaluated at baseline and at three-month and nine-month examination visits. At each visit (at 3 and 9 months), the subjects were also evaluated for glycaemic variables such as fasting plasma glucose (FPG) and HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels. RESULTS At the three-month follow-up, the subjects treated with dulaglutide showed significantly lower serum levels of FPG and HbA1c than control subjects treated with conventional therapy. At the 9-month follow-up, subjects treated with dulaglutide showed significant lower values of the mean diastolic blood pressure, BMI, total serum cholesterol, LDL cholesterol, FPG, HbA1c and PWV and higher mean RHI values than control subjects treated with conventional therapy. CONCLUSIONS Our randomized trial showed that subjects with type 2 diabetes treated with conventional therapy plus 1.5 mg/day of subcutaneous dulaglutide compared with subjects treated with conventional therapy alone showed favourable metabolic effects associated with positive effects on vascular health markers such as arterial stiffness and endothelial function markers. These findings are consistent with previous study findings indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.
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Acute resveratrol supplementation in coronary artery disease: towards patient stratification.
Diaz, M, Avila, A, Degens, H, Coeckelberghs, E, Vanhees, L, Cornelissen, V, Azzawi, M
Scandinavian cardiovascular journal : SCJ. 2020;(1):14-19
Abstract
Objective: Resveratrol (RV) is a polyphenol with antioxidant, anti-inflammatory and cardio-protective properties. Our objective was to investigate whether acute supplementation with high doses of RV would improve flow-mediated dilation (FMD) and oxygen consumption (VO2) kinetics in older coronary artery disease (CAD) patients. Design: We employed a placebo-controlled, single-blind, crossover design in which ten participants (aged 66.6 ± 7.8 years) received either RV or placebo (330 mg, 3× day-1) during three consecutive days plus additional 330 mg in the morning of the fourth day with a seven-day wash-out period in-between. On the fourth day, FMD of the brachial artery and VO2 on-kinetics were determined. Results: RV improved FMD in patients who had undergone coronary artery bypass grafting (CABG; -1.4 vs. 5.0%; p = .004), but not in those who had undergone percutaneous coronary intervention (PCI; 4.2 vs. -0.2%; NS). Conclusion: Acute high dose supplementation with RV improved FMD in patients after CABG surgery but impaired FMD in patients who underwent PCI. The revascularization method-related differential effects of RV may be due to its direct effects on endothelial-dependent dilator responses. Our findings have important implications for personalized treatment and stratification of older CAD patients.
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Acute consumption of flavanol-rich cocoa beverage improves attenuated cutaneous microvascular function in healthy young African Americans.
Kim, K, Brothers, RM
Microvascular research. 2020;:103931
Abstract
Flavanols have beneficial effects on vascular health and we have recently demonstrated that cerebral vasodilatory capacity in healthy young African Americans (AA) is improved with acute flavanol intake relative to aged-matched Caucasian Americans (CA). However, whether the positive benefits of acute flavanol consumption would also be present in the cutaneous microvascular circulation of AA remains unknown. Thus, we hypothesized that acute consumption of flavanol-rich cocoa (FC) would improve the previously reported reduced cutaneous microvascular responses to local heating in young AA. Seven AA and seven CA participated in this double-blind crossover study. Data were collected on two different days, separated by a minimum of one week. Two intradermal microdialysis membranes were inserted in the forearm and each site was randomly assigned to receive lactated Ringer's solution or NO synthase (NOS) inhibitor. Participants were randomly assigned to consume either a non-flavanol containing (NF) beverage or FC beverage. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flux/mean arterial pressure and normalized as % maximal CVC (%CVCmax). The difference in %CVCmax between the Ringer's site and NOS inhibited site was calculated to assess NO contribution (Δ %CVCmax). In the Ringer's site, acute consumption of FC beverage improved %CVCmax during 39 °C heating when compared to NF beverage in AA (NF: 36 ± 6 vs. FC: 47 ± 5%CVCmax; P < .01) while there was similar %CVCmax during 39 °C heating between beverages in CA (NF: 55 ± 4 vs. FC: 59 ± 5%CVCmax; P = .40). During 39 °C heating, NO contribution was significantly higher with FC beverage than NF beverage in AA (NF: 27 ± 5 vs. FC: 35 ± 4 Δ %CVCmax; P = .03) while there was similar NO contribution between beverages in CA (NF: 42 ± 4 vs. FC: 45 ± 4 Δ %CVCmax; P = .36). This data suggests that acute consumption of FC could be a therapeutic solution to improve an attenuated microvascular function in young AA.
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Increased fractalkine and vascular dysfunction in obesity and in type 2 diabetes. Effects of oral antidiabetic treatment.
Schinzari, F, Tesauro, M, Campia, U, Cardillo, C
Vascular pharmacology. 2020;:106676
Abstract
Activation of fractalkine and other chemokines plays an important role in atherogenesis and, in conjunction with endothelial dysfunction, promotes premature vascular damage in obesity and diabetes. We hypothesized that increased circulating fractalkine coexists with impaired vasomotor function in metabolically healthy or unhealthy obesity, and that treatment with antidiabetic drugs may impact these abnormalities in type 2 diabetes. Compared to lean subjects, in both obese groups the vasodilator responses to acetylcholine and sodium nitroprusside were impaired (both P < .001); ETA-receptor blockade resulted in greater vasodilation (both P < .001); and plasma levels of fractalkine, E-selectin and monocyte chemoattractant protein (MCP)-1 were increased (all P < .05). In diabetic patients, oral antidiabetic drugs (glyburide, metformin or pioglitazone) reduced circulating levels fractalkine and E-selectin (both P < .05), without affecting vascular responses (all P > .05). Our findings indicate that insulin resistant states are associated with elevated atherogenic chemokines and impaired vascular reactivity. Antidiabetic treatment results in lower circulating fractalkine, which may provide cardiovascular benefits.