Increases in muscle blood flow after a mixed meal are impaired at all stages of 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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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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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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Association of Exercise Intolerance in Type 2 Diabetes With Skeletal Muscle Blood Flow Reserve

JACC Cardiovascular Imaging ◽

10.1016/j.jcmg.2014.12.033 ◽

2015 ◽

Vol 8 (8) ◽

pp. 913-921 ◽

Cited By ~ 17

Author(s):

Julian W. Sacre ◽

Christine L. Jellis ◽

Brian A. Haluska ◽

Carly Jenkins ◽

Jeff S. Coombes ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Blood Flow ◽

Muscle Blood Flow ◽

Exercise Intolerance ◽

Skeletal Muscle Blood Flow ◽

Flow Reserve

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1715-P: Impaired Postprandial Adipose Tissue Microvascular Blood Flow in Healthy People with a Family History of Type 2 Diabetes

Diabetes ◽

10.2337/db20-1715-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1715-P

Author(s):

KATHERINE ROBERTS-THOMSON ◽

RYAN D. RUSSELL ◽

DONGHUA HU ◽

TIMOTHY M. GREENAWAY ◽

ANDREW C. BETIK ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Flow ◽

Adipose Tissue ◽

Family History ◽

Healthy People ◽

Microvascular Blood Flow ◽

History Of

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226 THE EFFECTS OF CONTRAST BATHS ON SKIN BLOOD FLOW IN PEOPLE WITH TYPE 2 DIABETES AND AGE-MATCHED CONTROLS.

Journal of Investigative Medicine ◽

10.2310/6650.2005.x0004.225 ◽

2006 ◽

Vol 54 (1) ◽

pp. S118.6-S119 ◽

Cited By ~ 1

Author(s):

B. D. Moseley ◽

R. Korson ◽

J. Petrofsky ◽

E. Lohman ◽

S. Lee ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Flow ◽

Skin Blood Flow

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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.

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A Mixed Meal Potentiates the Insulin Sensitivity of Glucose Transport and Metabolism in Adipocytes from Patients with Type 2 Diabetes Mellitus

Diabetic Medicine ◽

10.1111/j.1464-5491.1988.tb01104.x ◽

1988 ◽

Vol 5 (8) ◽

pp. 761-765

Author(s):

A. Lange ◽

J. Bak ◽

P. H. Andersen ◽

B. Richelsen ◽

O. Pedersen

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Sensitivity ◽

Glucose Transport ◽

Mixed Meal

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00234.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. E1242-E1250 ◽

Cited By ~ 1

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.

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