Acute Effects of Interrupting Prolonged Sitting on Vascular Function in Type 2 Diabetes

In healthy and overweight/obese adults, interrupting prolonged sitting with activity bouts mitigates impairment in vascular function. However, it is unknown whether these benefits extend to those with type 2 diabetes (T2D); nor, whether an optimal frequency of activity interruptions exist. We examined the acute effects on vascular function in T2D of interrupting prolonged sitting with simple resistance activities (SRA) at different frequencies. In a randomized crossover trial, 24 adults with T2D (35-70 years) completed three 7-hour conditions: 1) uninterrupted sitting (SIT); 2) sitting with 3 minute bouts of SRA every 30 min (SRA3); and, 3) sitting with 6 minute bouts of SRA every 60 min (SRA6). Femoral artery flow-mediated dilation (FMD), resting shear rate, blood flow and endothelin-1 were measured at 0h, 1h, 3.5h, 4.5h, and 6.5-7h. Mean femoral artery FMD over 7 hours was significantly higher in SRA3 (4.1 ± 0.3%) compared to SIT (3.7 ± 0.3%, p = 0.04), but not in SRA6. Mean resting femoral shear rate over 7 hours was increased significantly for SRA3 (45.3±4.1/s, p<0.001) and SRA6 (46.2±4.1/s, p<0.001) relative to SIT (33.1±4.1/s). Endothelin-1 concentrations were not statistically different between conditions. Interrupting sitting with activity breaks every 30 minutes, but not 60 minutes, significantly increased mean femoral artery FMD over 7 hours, relative to SIT. Our findings suggest that more-frequent and shorter breaks may be more beneficial than longer, less-frequent breaks for vascular health in those with T2D.

Download Full-text

Simple intermittent resistance activity mitigates the detrimental effect of prolonged unbroken sitting on arterial function in overweight and obese adults

Journal of Applied Physiology ◽

10.1152/japplphysiol.00544.2018 ◽

2018 ◽

Vol 125 (6) ◽

pp. 1787-1794 ◽

Cited By ~ 12

Author(s):

Rachel E. Climie ◽

Michael J. Wheeler ◽

Megan Grace ◽

Elisabeth A. Lambert ◽

Neale Cohen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Shear Rate ◽

Adhesion Molecule ◽

Femoral Artery ◽

Sitting Time ◽

Cvd Risk ◽

Obese Adults ◽

Arterial Function ◽

Endothelin 1 ◽

Prolonged Sitting

Prolonged sitting contributes to cardiovascular disease (CVD) risk. The underlying mechanisms are unknown but may include changes in arterial function and vasoactive mediators. We examined the effects of prolonged unbroken sitting, relative to regular active interruptions to sitting time, on arterial function in adults at increased CVD risk. In a randomized crossover trial, 19 sedentary overweight/obese adults (mean ± SD age 57 ± 12 yr) completed 2 laboratory-based conditions: 5 h uninterrupted sitting (SIT) and 5 h sitting interrupted every 30 min by 3 min of simple resistance activities (SRA). Femoral artery function [flow-mediated dilation (FMD)], blood flow, and shear rate were measured at 0 h, 30 min, 1 h, 2 h, and 5 h. Brachial FMD was assessed at 0 and 5 h. Plasma was collected hourly for measurement of endothelin-1 (ET-1), nitrates/nitrites, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). There was a significant decline in femoral artery FMD, averaged over 5 h in the SIT condition, relative to SRA ( P < 0.001). Plasma ET-1 total area under the curve over 5 h increased in the SIT condition compared with SRA ( P = 0.006). There was no significant difference between conditions in femoral or brachial shear rate, brachial FMD, nitrates/nitrites, VCAM-1, or ICAM-1 ( P > 0.05 for all). Five hours of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating ET-1 in overweight/obese adults. There is the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting. NEW & NOTEWORTHY This is the first study to examine the effect of prolonged sitting on arterial function in adults at increased cardiovascular disease risk. We have shown that 5 h of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating endothelin-1 in overweight/obese adults. There is now the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.

Download Full-text

Acute Effects Of Interrupting Prolonged Sitting On Vascular Function In Type 2 Diabetes

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000670104.57762.50 ◽

2020 ◽

Vol 52 (7S) ◽

pp. 14-14

Author(s):

Frances Clare Taylor ◽

David W. Dunstan ◽

Ashleigh R. Homer ◽

Bronwyn A. Kingwell ◽

Paddy C. Dempsey ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vascular Function ◽

Acute Effects ◽

Prolonged Sitting

Download Full-text

7-OR: Effect of Dapagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, on Vascular Function in Patients with Type 2 Diabetes Compared with Gliclazide

Diabetes ◽

10.2337/db19-7-or ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 7-OR

Author(s):

SOO LIM ◽

DAVID CHERNEY

Keyword(s):

Type 2 Diabetes ◽

Vascular Function ◽

Sodium Glucose Cotransporter

Download Full-text

Metabolic and endothelial effects of trimetazidine on forearm skeletal muscle in patients with type 2 diabetes and ischemic cardiomyopathy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00083.2005 ◽

2006 ◽

Vol 290 (1) ◽

pp. E54-E59 ◽

Cited By ~ 35

Author(s):

Lucilla D. Monti ◽

Emanuela Setola ◽

Gabriele Fragasso ◽

Riccardo P. Camisasca ◽

Pietro Lucotti ◽

...

Keyword(s):

Type 2 Diabetes ◽

Lipid Oxidation ◽

Ischemic Cardiomyopathy ◽

Glucose Oxidation ◽

Diabetic Patients ◽

Vascular Effects ◽

Type 2 Diabetic Patients ◽

Double Blind ◽

Endothelin 1

The aim of the present study was to evaluate the effect of prolonged inhibition of β-oxidation on glucose and lipid muscle forearm metabolism and cGMP and endothelin-1 forearm release in patients with type 2 diabetes mellitus and ischemic cardiomyopathy. Fifteen patients were randomly allocated in a double-blind cross-over parallel study with trimetazidine (20 mg tid) or placebo lasting 15 days. At the end of each period, all patients underwent euglycemic hyperinsulinemic clamps with forearm indirect calorimetry and endothelial balance of vasodilator and vasoconstricor factors. Compared with placebo, trimetazidine induced 1) an increase in insulin-induced forearm glucose uptake and glucose oxidation accompained by a reduction in forearm lipid oxidation and citrate release and 2) a decrease of endothelin-1 release paralleled by a significant increase in forearm cGMP release. Forearm glucose oxidation significantly correlated with cGMP release ( r = 0.37, P < 0.04), whereas forearm lipid oxidation positively correlated with endothelin-1 release ( r = 0.40, P < 0.03). In conclusion, for the first time, we demonstrated that insulin-induced forearm glucose oxidation and forearm cGMP release were increased whereas forearm endothelin-1 release was decreased during trimetazidine treatment. Muscle's metabolic and vascular effects of trimetazidine add new interest in the use of trimetazidine in type 2 diabetic patients with cardiovascular disease.

Download Full-text

Effects of three types of bariatric interventions on myocardial infarct size and vascular function in rats with type 2 diabetes mellitus

Life Sciences ◽

10.1016/j.lfs.2021.119676 ◽

2021 ◽

pp. 119676

Author(s):

Oleg V. Kornyushin ◽

Dmitry L. Sonin ◽

Alexander S. Polozov ◽

Vitaly V. Masley ◽

Maria S. Istomina ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Infarct Size ◽

Vascular Function ◽

Myocardial Infarct ◽

Myocardial Infarct Size

Download Full-text

Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1

Journal of Applied Physiology ◽

10.1152/japplphysiol.00286.2016 ◽

2017 ◽

Vol 122 (1) ◽

pp. 38-47 ◽

Cited By ~ 30

Author(s):

Leryn J. Reynolds ◽

Daniel P. Credeur ◽

Camila Manrique ◽

Jaume Padilla ◽

Paul J. Fadel ◽

...

Keyword(s):

Nitric Oxide ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Blood Flow ◽

Vastus Lateralis ◽

Glucose Disposal ◽

Endothelin 1 ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients. NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

Download Full-text

An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0224 ◽

2020 ◽

Vol 45 (4) ◽

pp. 397-404

Author(s):

Tugba Gurpinar Çavuşoğlu ◽

Ertan Darıverenli ◽

Kamil Vural ◽

Nuran Ekerbicer ◽

Cevval Ulman ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Endothelial Dysfunction ◽

Vascular Function ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Diabetic Rat ◽

Insulin Levels ◽

Type 2 Diabetic

AbstractObjectivesType 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats.MethodsA type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated.ResultsBoth doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels.ConclusionsBuspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.

Download Full-text

Endothelin-1 predicts incident diabetic peripheral neuropathy in Type 2 Diabetes: a cohort study

Acta Endocrinologica ◽

10.1530/eje-19-0523 ◽

2020 ◽

Vol 182 (4) ◽

pp. 429-438

Author(s):

Sharon Li Ting Pek ◽

Su Chi Lim ◽

Keven Ang ◽

Pek Yee Kwan ◽

Wern Ee Tang ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Cohort Study ◽

Peripheral Neuropathy ◽

Diabetic Peripheral Neuropathy ◽

Diabetes Duration ◽

Endothelin 1

Introduction Diabetic peripheral neuropathy (DPN) is a common microvascular complication in patients with type 2 diabetes (T2D). Apart from hyperglycemia, few modifiable risk factors have been identified. Endothelin-1 is a potent vasoconstrictor peptide, implicated in the causal pathway of microangiopathy. We investigated whether baseline plasma endothelin-1 and other metabolic and vascular risk factors predicted the incidence of DPN. Design This is a 3-year observational, cohort study. Methods In patients with T2D (n = 2057), anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements. Forearm cutaneous endothelial reactivity was assessed by iontophoresis and laser Doppler flowmetry/imaging. Measurements were repeated on follow-up. Incident DPN was considered present if an abnormal finding in monofilament (<8 of 10 points) or neurothesiometer testing was ≥25 volts on either foot at 3-year follow-up, but normal at baseline. Plasma endothelin-1 was assessed by ELISA. Results At baseline, mean age of patients was 57.4 ± 10.8 years old and prevalence of DPN was 10.8%. Of the 1767 patients without DPN, 1250 patients returned for follow-up assessment ((2.9 ± 0.7) years), with a 10.7% incidence of DPN. Patients with incident DPN had significantly higher baseline endothelin-1 (1.43 (1.19–1.73) vs 1.30 (1.06–1.63)) pg/mL, P < 0.0001. Multivariable Cox proportional hazards ratio showed a 1-s.d. increase in log endothelin-1 (adjusted HR: 4.345 (1.451–13.009), P = 0.009), systolic blood pressure (per 10-unit) (adjusted HR: 1.107 (1.001–1.223), P = 0.047) and diabetes duration (adjusted HR: 1.025 (1.004–1.047), P = 0.017) predicted incident DPN, after adjustment for glycemic control, eGFR, albuminuria, peripheral arterial disease and retinopathy status. Conclusion Higher baseline endothelin-1, blood pressure and diabetes duration were significant and independent predictors for incident DPN. Validation of our findings in independent cohorts and molecular mechanistic studies will help better our understanding on the role of endothelin-1 in DPN.

Download Full-text