Association of Exercise Intolerance in Type 2 Diabetes With Skeletal Muscle Blood Flow Reserve

Sacre, Julian W.; Jellis, Christine; Haluska, Brian; Jenkins, Carly; Coombes, Jeff S.; Marwick, Thomas H.; Keske, Michelle A.

doi:10.1016/j.jcmg.2014.12.033

Cited by 30 publications

(40 citation statements)

References 26 publications

(17 reference statements)

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“…Our model predicts that the rarefaction of capillaries within skeletal muscle causes overall lower tissue PO 2 and a more variable distribution of oxygen throughout a tissue volume. This result may inform experimental findings that associate the decrease in CD in prediabetes and type 2 diabetes with exercise intolerance because decreased tissue PO 2 would limit the work capacity of muscle.…”

Section: Discussionsupporting

confidence: 57%

A computational model of the effect of capillary density variability on oxygen transport, glucose uptake, and insulin sensitivity in prediabetes

2017

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Section: Discussionsupporting

confidence: 57%

A computational model of the effect of capillary density variability on oxygen transport, glucose uptake, and insulin sensitivity in prediabetes

2017

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“…However, other studies did not observe impaired Doppler indices, but reported LV size as a predictor of reduced oxygen uptake [45]. Finally, cardiac index reserve, a variable expressed by the combination of chronotropic index and SV index reserve, appears related to VO 2max as well [46], thus strengthening the possibility of causal link between subclinical diabetic cardiac myopathy and reduced exercise capacity in T2DM. Unfortunately, associations do not provide information on the causal relationships, therefore it would be more informative to evaluate the full VO 2 /cardiac index curves and, more importantly, to verify whether VO 2peak can be normalized by pharmacologically improving the cardiac inotropic function.…”

Section: Myocardiogenic Determinantsmentioning

confidence: 85%

Type 2 diabetes and reduced exercise tolerance: a review of the literature through an integrated physiology approach

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Pugliese

Sciuto

et al. 2020

Cardiovasc Diabetol

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The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) is well established. Early in the course of the diabetic disease, some degree of impaired exercise capacity (a powerful marker of health status with prognostic value) can be frequently highlighted in otherwise asymptomatic T2DM subjects. However, the literature is quite heterogeneous, and the underlying pathophysiologic mechanisms are far from clear. Imaging-cardiopulmonary exercise testing (CPET) is a non-invasive, provocative test providing a multi-variable assessment of pulmonary, cardiovascular, muscular, and cellular oxidative systems during exercise, capable of offering unique integrated pathophysiological information. With this review we aimed at defying the cardiorespiratory alterations revealed through imaging-CPET that appear specific of T2DM subjects without overt cardiovascular or pulmonary disease. In synthesis, there is compelling evidence indicating a reduction of peak workload, peak oxygen assumption, oxygen pulse, as well as ventilatory efficiency. On the contrary, evidence remains inconclusive about reduced peripheral oxygen extraction, impaired heart rate adjustment, and lower anaerobic threshold, compared to non-diabetic subjects. Based on the multiparametric evaluation provided by imaging-CPET, a dissection and a hierarchy of the underlying mechanisms can be obtained. Here we propose four possible integrated pathophysiological mechanisms, namely myocardiogenic, myogenic, vasculogenic and neurogenic. While each hypothesis alone can potentially explain the majority of the CPET alterations observed, seemingly different combinations exist in any given subject. Finally, a discussion on the effects-and on the physiological mechanisms-of physical activity and exercise training on oxygen uptake in T2DM subjects is also offered. The understanding of the early alterations in the cardiopulmonary response that are specific of T2DM would allow the early identification of those at a higher risk of developing HF and possibly help to understand the pathophysiological link between T2DM and HF.

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“…Our study showed that %HRR and !O2 at VT in T2 DM were significantly lower than that in CON. The VT and !O2peak are parameters that have been widely considered as clinical markers of aerobic fitness 40,41) , and lower aerobic fitness in T2DM is widely recognized independent of cardiovascular disease or other comorbidities such as obesity 42 ) . Our result that VT in patients with T2DM was significantly lower than that in CON is agree with these previous studies 42,43 ) .…”

Section: Discussionmentioning

confidence: 99%

“…The VT and !O2peak are parameters that have been widely considered as clinical markers of aerobic fitness 40,41) , and lower aerobic fitness in T2DM is widely recognized independent of cardiovascular disease or other comorbidities such as obesity 42 ) . Our result that VT in patients with T2DM was significantly lower than that in CON is agree with these previous studies 42,43 ) . The VT depends on oxidative metabolism in the muscles ( mitochondorial density, oxidative enzymes and percentage slow-twitch myosin heavy chain types) and oxygen supply to the mitochondria (cardiac output, capillary density, haematocrit, arterial-venous oxygen difference, and oxygen diffusion) 44 ) .…”

Section: Discussionmentioning

confidence: 99%

Near-infrared Spectroscopy of Vastus Lateralis Muscle during Incremental Cycling Exercise in patients with Type 2 Diabetes

et al. 2020

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It is clinically important to elucidate the precise mechanism of exercise intolerance in patients with type 2 diabetes (T2DM). The aim of this study was to examine whether there is a difference in the time course change of the oxygenation in the vastus lateralis (VL) muscle during submaximal incremental cycling exercise between patients with T2DM and age-matched healthy subjects. Methods: Nine elderly men with T2DM and 10 age-matched healthy men (CON) participated in this study. All participants performed an incremental cycling exercise.Total, deoxygenated and oxygenated hemoglobin/myoglobin in the VL muscle were assessed using near-infrared spectroscopy, and cardiorespiratory response was also evaluated during the exercise. Results: There were no significant differences in the time course changes of deoxygenated hemoglobin/myoglobin between groups (p > 0.05). However, the oxygenated hemoglobin/myoglobin in T2DM was significantly higher than that in CON at an intensity above ventilatory threshold during the incremental cycling exercise (p< 0.05). Conclusion: This study suggests that patients with T2DM had early limitation of oxygen extraction and lower capacity of oxygenated myoglobin dissociation in the VL muscle. The fact that patients with T2DM showed different oxygen kinetics in a peripheral tissue from healthy subjects may partly explain the potential mechanisms of exercise intolerance in T2DM.

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Association of Exercise Intolerance in Type 2 Diabetes With Skeletal Muscle Blood Flow Reserve

Abstract: Vo2peak is associated with muscle CBF reserve in T2DM, independent of parallel associations with cardiac functional reserve. This is consistent with a multifactorial basis for exercise intolerance in T2DM.

Cited by 30 publications

References 26 publications

A computational model of the effect of capillary density variability on oxygen transport, glucose uptake, and insulin sensitivity in prediabetes

A computational model of the effect of capillary density variability on oxygen transport, glucose uptake, and insulin sensitivity in prediabetes

Type 2 diabetes and reduced exercise tolerance: a review of the literature through an integrated physiology approach

Near-infrared Spectroscopy of Vastus Lateralis Muscle during Incremental Cycling Exercise in patients with Type 2 Diabetes

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