Exercise-induced hyperemia is associated with knee extensor fatigability in adults with type 2 diabetes

The aim of this study was to compare fatigability, contractile function, and blood flow to the knee extensor muscles after dynamic exercise in patients with type 2 diabetes mellitus (T2DM) and controls. The hypotheses were that patients with T2DM would demonstrate greater fatigability than controls, and greater fatigability would be associated with a lower exercise-induced increase in blood flow and greater impairments in contractile function. Patients with T2DM ( n = 15; 8 men; 62.4 ± 9.0 yr; 30.4 ± 7.7 kg/m2; 7,144 ± 3,294 steps/day) and 15 healthy control subjects (8 men, 58.4 ± 6.9 yr; 28.4 ± 4.6 kg/m2; 7,893 ± 2,323 steps/day) were matched for age, sex, body mass index, and physical activity. Fatigability was quantified as the reduction in knee extensor power during a 6-min dynamic exercise. Before and after exercise, vascular ultrasonography and electrical stimulation were used to assess skeletal muscle blood flow and contractile properties, respectively. Patients with T2DM had greater fatigability (30.0 ± 20.1% vs. 14.6 ± 19.0%, P < 0.001) and lower exercise-induced hyperemia (177 ± 90% vs. 194 ± 79%, P = 0.04) than controls but similar reductions in the electrically evoked twitch amplitude (37.6 ± 24.8% vs. 31.6 ± 30.1%, P = 0.98). Greater fatigability of the knee extensor muscles was associated with postexercise reductions in twitch amplitude ( r = 0.64, P = 0.001) and lesser exercise-induced hyperemia ( r = −0.56, P = 0.009). Patients with T2DM had greater lower-limb fatigability during dynamic exercise, which was associated with reduced contractile function and lower skeletal muscle blood flow. Thus, treatments focused on enhancing perfusion and reversing impairments in contractile function in patients with T2DM may offset lower-limb fatigability and aid in increasing exercise capacity. NEW & NOTEWORTHY Although prior studies compare patients with type 2 diabetes mellitus (T2DM) with lean controls, our study includes controls matched for age, body mass, and physical activity to more closely assess the effects of T2DM. Patients with T2DM demonstrated no impairment in macrovascular endothelial function, evidenced by similar flow-mediated dilation to controls. However, patients with T2DM had greater fatigability and reduced exercise-induced increase in blood flow (hyperemia) after a lower-limb dynamic fatiguing exercise compared with controls.

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Mechanisms for the increased fatigability of the lower limb in people with type 2 diabetes

Journal of Applied Physiology ◽

10.1152/japplphysiol.00160.2018 ◽

2018 ◽

Vol 125 (2) ◽

pp. 553-566 ◽

Cited By ~ 7

Author(s):

Jonathon Senefeld ◽

Steven B. Magill ◽

April Harkins ◽

Alison R. Harmer ◽

Sandra K. Hunter

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Body Mass Index ◽

Magnetic Stimulation ◽

Knee Extensor ◽

Voluntary Activation ◽

Men And Women ◽

Extensor Muscles ◽

Knee Extensor Muscles

Fatiguing exercise is the basis of exercise training and a cornerstone of management of type 2 diabetes mellitus (T2D); however, little is known about the fatigability of limb muscles and the involved mechanisms in people with T2D. The purpose of this study was to compare fatigability of knee extensor muscles between people with T2D and controls without diabetes and determine the neural and muscular mechanisms for a dynamic fatiguing task. Seventeen people with T2D [ten men and seven women: 59.6 (9.0) yr] and twenty-one age-, body mass index-, and physical activity-matched controls [eleven men and ten women: 59.5 (9.6) yr] performed one hundred twenty high-velocity concentric contractions (one contraction/3 s) with a load equivalent to 20% maximal voluntary isometric contraction (MVIC) torque with the knee extensors. Transcranial magnetic stimulation (TMS) and electrical stimulation of the quadriceps were used to assess voluntary activation and contractile properties. People with T2D had larger reductions than controls in power during the fatiguing task [42.8 (24.2) vs. 26.4 (15.0)%; P < 0.001] and MVIC torque after the fatiguing task [37.6 (18.2) vs. 26.4 (12.1)%; P = 0.04]. People with T2D had greater reductions than controls in the electrically evoked twitch amplitude after the fatiguing task [44.0 (20.4) vs. 35.4 (12.1)%, respectively; P = 0.01]. However, the decrease in voluntary activation was similar between groups when assessed with electrical stimulation [12.1 (2.6) vs. 12.4 (4.4)% decrease; P = 0.84] and TMS ( P = 0.995). A greater decline in MVIC torque was associated with larger reductions of twitch amplitude ( r2 = 0.364, P = 0.002). Although neural mechanisms contributed to fatigability, contractile mechanisms were responsible for the greater knee extensor fatigability in men and women with T2D compared with healthy controls. NEW & NOTEWORTHY Transcranial magnetic stimulation and percutaneous muscle stimulation were used to determine the contributions of neural and contractile mechanisms of fatigability of the knee extensor muscles after a dynamic fatiguing task in men and women with type 2 diabetes (T2D) and healthy age-, body mass index-, and physical activity-matched controls. Although neural and contractile mechanisms contributed to greater fatigability of people with T2D, fatigability was primarily associated with impaired contractile mechanisms and glycemic control.

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Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus

Experimental Physiology ◽

10.1113/expphysiol.2013.077297 ◽

2014 ◽

Vol 99 (9) ◽

pp. 1253-1264 ◽

Cited By ~ 9

Author(s):

Tim H. A. Schreuder ◽

Jaap H. van Lotringen ◽

Maria T. E. Hopman ◽

Dick H. J. Thijssen

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Blood Flow ◽

Type 2 Diabetes Mellitus ◽

Endothelial Function ◽

Acute Exercise ◽

Exercise Induced ◽

Induced Changes

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Role of α1-adrenergic vasoconstriction in the regulation of skeletal muscle blood flow with advancing age

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01016.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. H497-H504 ◽

Cited By ~ 28

Author(s):

D. Walter Wray ◽

Steven K. Nishiyama ◽

Russell S. Richardson

Keyword(s):

Blood Flow ◽

Muscle Blood Flow ◽

Knee Extensor ◽

The Elderly ◽

Work Rate ◽

Leg Blood Flow ◽

Vasoconstrictor Response ◽

Leg Exercise ◽

Exercise Induced ◽

Induced Changes

α1-Adrenergic vasoconstriction during dynamic leg exercise is diminished in younger individuals, although the extent of this exercise-induced “sympatholysis” in the elderly remains uncertain. Thus, in nine young (25 ± 1 yr) and six older (72 ± 2 yr) healthy volunteers, we evaluated changes in leg blood flow (ultrasound Doppler) during blood flow-adjusted intra-arterial infusion of phenylephrine (PE; a selective α1-adrenergic agonist) at rest and during knee-extensor leg exercise at 20, 40, and 60% of maximal work rate (WRmax). To probe the potential contributors to exercise-induced changes in α1-adrenergic receptor sensitivity, exercising leg O2 consumption (V̇o2) and lactate efflux were also evaluated ( n = 10). At rest, the PE-induced vasoconstriction (i.e., decrease in leg blood flow) was diminished in older (−37 ± 3%) compared with young (−54 ± 4%) subjects. During exercise, the magnitude of α1-adrenergic vasoconstriction in the active leg decreased in both groups. However, compared with young, older subjects maintained a greater vasoconstrictor response to PE at 40% WRmax (−14 ± 3%, older; −7 ± 2%, young) and 60% WRmax (−11 ± 3%, older; −4 ± 3%, young). It is possible that this observation may be attributed to lower absolute work rates in the older group, because, for a similar absolute work rate (≈10 W) and leg V̇o2 (≈0.36 l/min), vasoconstriction to PE was not different between groups (−14 ± 3%; older; −17 ± 5%, young). Together, these data challenge the concept of reduced sympatholysis in the elderly, suggesting instead that the inhibition of α1-adrenergic vasoconstriction in the exercising leg is associated with work performed and, therefore, more closely related to the rate of oxidative metabolism than to age per se.

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Taming the “sleeping giant”: the role of endothelin-1 in the regulation of skeletal muscle blood flow and arterial blood pressure during exercise

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00603.2012 ◽

2013 ◽

Vol 304 (1) ◽

pp. H162-H169 ◽

Cited By ~ 29

Author(s):

Zachary Barrett-O'Keefe ◽

Stephen J. Ives ◽

Joel D. Trinity ◽

Garrett Morgan ◽

Matthew J. Rossman ◽

...

Keyword(s):

Blood Flow ◽

Cardiovascular Response ◽

Muscle Blood Flow ◽

Knee Extensor ◽

Leg Blood Flow ◽

Arterial Blood ◽

Before And After ◽

Exercise Induced ◽

Response To Exercise

The cardiovascular response to exercise is governed by a combination of vasodilating and vasoconstricting influences that optimize exercising muscle perfusion while protecting mean arterial pressure (MAP). The degree to which endogenous endothelin (ET)-1, the body's most potent vasoconstrictor, participates in this response is unknown. Thus, in eight young (24 ± 2 yr), healthy volunteers, we examined leg blood flow, MAP, tissue oxygenation, heart rate, leg arterial-venous O2 difference, leg O2 consumption, pH, and net ET-1 and lactate release at rest and during knee extensor exercise (0, 5, 10, 15, 20, and 30 W) before and after an intra-arterial infusion of BQ-123 [ET subtype A (ETA) receptor antagonist]. At rest, BQ-123 did not evoke a change in leg blood flow or MAP. During exercise, net ET-1 release across the exercising leg increased approximately threefold. BQ-123 increased leg blood flow by ∼20% across all work rates (changes of 113 ± 76, 176 ± 83, 304 ± 108, 364 ± 130, 502 ± 117, and 570 ± 178 ml/min at 0, 5, 10, 15, 20, and 30 W, respectively) and attenuated the exercise-induced increase in MAP by ∼6%. The increase in leg blood flow was accompanied by a ∼9% increase in leg O2 consumption with an unchanged arterial-venous O2 difference and deoxyhemoglobin, suggesting a decline in intramuscular efficiency after ETA receptor blockade. Together, these findings identify a significant role of the ET-1 pathway in the cardiovascular response to exercise, implicating vasoconstriction via the ETA receptor as an important mechanism for both the restraint of blood flow in the exercising limb and maintenance of MAP in healthy, young adults.

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Lack of independent effect of type 2 diabetes beyond characteristic comorbidities and medications on small muscle mass exercising muscle blood flow and exercise tolerance

Physiological Reports ◽

10.14814/phy2.12487 ◽

2015 ◽

Vol 3 (8) ◽

pp. e12487 ◽

Cited By ~ 2

Author(s):

Veronica J. Poitras ◽

Robert F. Bentley ◽

Diana H. Hopkins-Rosseel ◽

Stephen A. LaHaye ◽

Michael E. Tschakovsky

Keyword(s):

Type 2 Diabetes ◽

Blood Flow ◽

Muscle Mass ◽

Exercise Tolerance ◽

Muscle Blood Flow ◽

Independent Effect ◽

Small Muscle

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Immediate Effect of Whole-Body Vibration on Skin Temperature and Lower-Limb Blood Flow in Older Adults with Type 2 Diabetes: Pilot Study

Applied Sciences ◽

10.3390/app10020690 ◽

2020 ◽

Vol 10 (2) ◽

pp. 690 ◽

Cited By ~ 1

Author(s):

Kennedy Freitas Pereira Alves ◽

Ana Paula de Lima Ferreira ◽

Luana Caroline de Oliveira Parente ◽

François Talles Medeiros Rodrigues ◽

Thais Vitorino Marques ◽

...

Keyword(s):

Type 2 Diabetes ◽

Older Adults ◽

Blood Flow ◽

Skin Temperature ◽

Lower Limb ◽

Whole Body Vibration ◽

Whole Body ◽

Limb Blood Flow ◽

Body Vibration

The purpose of this study was to evaluate the response of a single whole-body vibration (WBV) training session to peripheral skin temperature and peripheral blood flow of older adults with type 2 diabetes. A double-blind, controlled clinical trial was conducted following the Consolidated Standards of Reporting Trials (CONSORT) guidelines. A single session of WBV (24 Hz; amplitude 4 mm; vibration time 45 s, with a series of eight repetitions with recovery between repetitions of 30 s; total time of 10 min) or sham vibration on the Kikos P204 Vibrating Platform was employed. To assess skin temperature, the FLIR E40bxs thermographic camera and the ultrasonic vascular Doppler for flow velocity were used. Evaluation occurred before and after a WBV or sham intervention. The sample consisted of three men and 17 women. In the WBV group, there was a decrease in the temperature from 29.7 °C (±1.83) to 26.6 °C (±2.27), with p = 0.01. Temperature following sham decreased from 28.6 °C (±1.84) to 26.3 °C (±2.49), with p = 0.01. Regarding blood flow, there was a decrease in the analyzed arteries, especially the left posterior tibial artery, where there was a statistically significant flow reduction from 27.1 m/s (±25.36) to 20.5 m/s (±19.66), post WBV (p = 0.01). In the sham group, an increased flow velocity was observed for all the arteries analyzed, except for the left dorsal artery. Immediately following a full-body vibration session, peripheral skin temperature and lower-limb blood flow tend to decrease in diabetic patients. However, from the design of study developed, we cannot infer the maintenance of this effect in the medium and long term.

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Postexercise Hemodynamics in Patients With Type 2 Diabetes: Effect of Exercise Intensity and Duration

Journal of Clinical Exercise Physiology ◽

10.31189/2165-6193-6.1.1 ◽

2017 ◽

Vol 6 (1) ◽

pp. 1-8

Author(s):

Thomas K. Pellinger ◽

Catherine B. Pearce ◽

Grant H. Simmons ◽

Jack L. Snitzer

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Blood Flow ◽

Systolic Blood Pressure ◽

Vascular Function ◽

Muscle Blood Flow ◽

Vascular Conductance ◽

Femoral Blood Flow ◽

Femoral Blood

Background: For individuals with type 2 diabetes (T2D), the hemodynamic response to regular exercise is critical for regulating blood glucose, protecting vascular function, and reducing cardiovascular disease risk, but the hemodynamic responses to differing doses of acute exercise in T2D are unclear. We aimed to compare postexercise (PE) hemodynamics in patients with T2D in response to 4 doses of dynamic exercise. Methods: Eight subjects with well-controlled T2D (42–64 years old.; hemoglobin A1c: 6.6% ± 0.9%) participated in 4 study days, during which they exercised on a cycle ergometer at 4 different combinations of exercise duration and intensity: 30 min at 40% V˙O2peak (30@40), 30 min at 60% V˙O2peak (30@60), 60 min at 40% V˙O2peak (60@40), and 60 min at 60% V˙O2peak (60@60). Heart rate, arterial pressure, and femoral blood flow (Doppler ultrasound) were measured pre-exercise and every 15 min through 120 min PE. Femoral vascular conductance was calculated as flow/pressure. Results: Compared with pre-exercise baseline, femoral blood flow and femoral vascular conductance were higher through at least 105 min of recovery in all conditions (all P < .05), except for the 30@40 trial. Compared with the pre-exercise measures, systolic blood pressure was lower through at least 75 min of recovery in all conditions (all P < .05), except for the 30@40 trial. Conclusion: These results suggest that exercise must be at least moderate in intensity or prolonged in duration (>30 min) to promote sustained PE elevations in skeletal muscle blood flow and reductions in systolic blood pressure in patients with T2D.

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Endothelin-1-mediated vasoconstriction at rest and during dynamic exercise in healthy humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00867.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. H2550-H2556 ◽

Cited By ~ 41

Author(s):

D. Walter Wray ◽

Steven K. Nishiyama ◽

Anthony J. Donato ◽

Mikael Sander ◽

Peter D. Wagner ◽

...

Keyword(s):

Blood Flow ◽

Exercise Intensity ◽

Muscle Blood Flow ◽

Knee Extensor ◽

Dynamic Exercise ◽

Dependent Manner ◽

Drug Infusion ◽

Leg Blood Flow ◽

Healthy Humans ◽

Arterial Blood

It is now generally accepted that α-adrenoreceptor-mediated vasoconstriction is attenuated during exercise, but the efficacy of nonadrenergic vasoconstrictor pathways during exercise remains unclear. Thus, in eight young (23 ± 1 yr), healthy volunteers, we contrasted changes in leg blood flow (ultrasound Doppler) before and during intra-arterial infusion of the α1-adrenoreceptor agonist phenylephrine (PE) with that of the nonadrenergic endothelin A (ETA)/ETB receptor agonist ET-1. Heart rate, arterial blood pressure, common femoral artery diameter, and mean blood velocity were measured at rest and during knee-extensor exercise at 20%, 40%, and 60% of maximal work rate (WRmax). Drug infusion rates were adjusted for blood flow to maintain comparable doses across all subjects and conditions. At rest, PE infusion (8 ng·ml−1·min−1) provoked a rapid and significant decrease in leg blood flow (−51 ± 3%) within 2.5 min. Resting ET-1 infusion (40 pg·ml−1·min−1) significantly decreased leg blood flow within 5 min, reaching a maximal vasoconstriction (−34 ± 3%) after 25–30 min of continuous infusion. Compared with rest, an exercise intensity-dependent attenuation to PE-mediated vasoconstriction was observed (−18 ± 5%, −7 ± 2%, and −1 ± 3% change in leg blood flow at 20%, 40%, and 60% of WRmax, respectively). Vasoconstriction in response to ET-1 was also blunted in an exercise intensity-dependent manner (−13 ± 3%, −7 ± 4%, and 2 ± 3% change in leg blood flow at 20%, 40%, and 60% of WRmax, respectively). These findings support a significant contribution of ET-1 and α-adrenergic receptors in the regulation of skeletal muscle blood flow in the human leg at rest and suggest a similar, intensity-dependent “lysis” of peripheral ET and α-adrenergic vasoconstriction during dynamic exercise.

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