Leg Blood Flow and Fatigability In People With Type 2 Diabetes

2017 ◽  
Vol 49 (5S) ◽  
pp. 912
Author(s):  
Jonathon Senefeld ◽  
Kathleen M. Lukaszewicz ◽  
Jacqueline K. Limberg ◽  
Sandra K. Hunter
Author(s):  
Stine Høyer Finsen ◽  
Mie Rytz Hansen ◽  
Pernille B Lærkegaard Hansen ◽  
Stefan P Mortensen

Abstract Context Individuals with type 2 diabetes have an increased risk of endothelial dysfunction and cardiovascular disease. Plasma aldosterone could contribute by reactive oxygen species–dependent mechanisms by inducing a shift in the balance between a vasoconstrictor and vasodilator response to aldosterone. Objective We aimed to investigate the acute vascular effects of aldosterone in individuals with type 2 diabetes compared with healthy controls and if infusion of an antioxidant (n-acetylcysteine [NAC]) would alter the vascular response. Methods In a case–control design, 12 participants with type 2 diabetes and 14 healthy controls, recruited from the general community, were studied. Leg hemodynamics were measured before and during aldosterone infusion (0.2 and 5 ng min–1 [L leg volume]–1) for 10 minutes into the femoral artery with and without coinfusion of NAC (125 mg kg–1 hour–1 followed by 25 mg kg–1 hour–1). Leg blood flow and arterial blood pressure was measured, and femoral arterial and venous blood samples were collected. Results Compared with the control group, leg blood flow and vascular conductance decreased during infusion of aldosterone at the high dose in individuals with type 2 diabetes, whereas coinfusion of NAC attenuated this response. Plasma aldosterone increased in both groups during aldosterone infusion and there was no difference between groups at baseline or during the infusions. Conclusion These results suggests that type 2 diabetes is associated with a vasoconstrictor response to physiological levels of infused aldosterone and that the antioxidant NAC diminishes this response.


2008 ◽  
Vol 40 (4) ◽  
pp. 612-617 ◽  
Author(s):  
SOPHIE LALANDE ◽  
SILMARA GUSSO ◽  
PAUL L. HOFMAN ◽  
JAMES C. BALDI

2013 ◽  
Vol 113 (9) ◽  
pp. 2245-2252 ◽  
Author(s):  
Borja Sañudo ◽  
Rosa Alfonso-Rosa ◽  
Borja del Pozo-Cruz ◽  
Jesus del Pozo-Cruz ◽  
Delfín Galiano ◽  
...  

2000 ◽  
Vol 279 (5) ◽  
pp. E1097-E1103 ◽  
Author(s):  
Mikaela Sjöstrand ◽  
Agneta Holmäng ◽  
Lena Strindberg ◽  
Peter Lönnroth

Previous measurement of insulin in human muscle has shown that interstitial muscle insulin and glucose concentrations are ∼30–50% lower than in plasma during hyperinsulinemia in normal subjects. The aims of this study were to measure interstitial muscle insulin and glucose in patients with type 2 diabetes to evaluate whether transcapillary transport is part of the peripheral insulin resistance. Ten patients with type 2 diabetes and ten healthy controls matched for sex, age, and body mass index were investigated. Plasma and interstitial insulin, glucose, and lactate (measured by intramuscular in situ-calibrated microdialysis) in the medial quadriceps femoris muscle were analyzed during a hyperinsulinemic euglycemic clamp. Blood flow in the contralateral calf was measured by vein plethysmography. At steady-state clamping, at 60–120 min, the interstitial insulin concentration was significantly lower than arterial insulin in both groups (409 ± 86 vs. 1,071 ± 99 pmol/l, P < 0.05, in controls and 584 ± 165 vs. 1,253 ± 82 pmol/l, P < 0.05, in diabetic subjects, respectively). Interstitial insulin concentrations did not differ significantly between diabetic subjects and controls. Leg blood flow was significantly higher in controls (8.1 ± 1.2 vs. 4.4 ± 0.7 ml · 100 g−1· min−1in diabetics, P < 0.05). Calculated glucose uptake was less in diabetic patients compared with controls (7.0 ± 1.2 vs. 10.8 ± 1.2 μmol · 100 g−1· min−1, P < 0.05, respectively). Arterial and interstitial lactate concentrations were both higher in the control group (1.7 ± 0.1 vs. 1.2 ± 0.1, P < 0.01, and 1.8 ± 0.1 vs. 1.2 ± 0.2 mmol/l, P < 0.05, in controls and diabetics, respectively). We conclude that, during hyperinsulinemia, muscle interstitial insulin and glucose concentrations did not differ between patients with type 2 diabetes and healthy controls despite a significantly lower leg blood flow in diabetic subjects. It is suggested that decreased glucose uptake in type 2 diabetes is caused by insulin resistance at the cellular level rather than by a deficient access of insulin and glucose surrounding the muscle cell.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1715-P
Author(s):  
KATHERINE ROBERTS-THOMSON ◽  
RYAN D. RUSSELL ◽  
DONGHUA HU ◽  
TIMOTHY M. GREENAWAY ◽  
ANDREW C. BETIK ◽  
...  

2006 ◽  
Vol 54 (1) ◽  
pp. S118.6-S119 ◽  
Author(s):  
B. D. Moseley ◽  
R. Korson ◽  
J. Petrofsky ◽  
E. Lohman ◽  
S. Lee ◽  
...  

2017 ◽  
Vol 122 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Leryn J. Reynolds ◽  
Daniel P. Credeur ◽  
Camila Manrique ◽  
Jaume Padilla ◽  
Paul J. Fadel ◽  
...  

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.


2018 ◽  
Vol 315 (6) ◽  
pp. E1242-E1250 ◽  
Author(s):  
Donghua Hu ◽  
Ryan D. Russell ◽  
Devika Remash ◽  
Timothy Greenaway ◽  
Stephen Rattigan ◽  
...  

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.


2015 ◽  
Vol 14 (1) ◽  
pp. 1008-1016 ◽  
Author(s):  
C. Ling ◽  
C.Y. Cai ◽  
B.C. Chang ◽  
W.T. Shi ◽  
F.J. Wei ◽  
...  

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