Abstract
Diabetes has reached worldwide epidemic proportions, and threatens to be a significant economic burden to both patients and healthcare systems, and an important driver of cardiovascular mortality and morbidity. Improvement in lifestyle interventions (which includes increase in physical activity via exercise) can reduce diabetes and cardiovascular disease mortality and morbidity. Encouraging a population to increase physical activity and exercise is not a simple feat particularly in individuals with co-morbidities (obesity, heart disease, stroke, peripheral vascular disease, and those with cognitive and physical limitations). Translation of the physiological benefits of exercise within that vulnerable population would be an important step for improving physical activity goals and a stopgap measure to exercise. In large part many of the beneficial effects of exercise are due to the introduction of pulsatile shear stress (PSS) to the vascular endothelium. PSS is a well-known stimulus for endothelial homeostasis, and induction of a myriad of pathways which include vasoreactivity, paracrine/endocrine function, fibrinolysis, inflammation, barrier function, and vessel growth and formation. The endothelial cell mediates the balance between vasoconstriction and relaxation via the major vasodilator endothelial derived nitric oxide (eNO). eNO is critical for vasorelaxation, increasing blood flow, and an important signaling molecule that downregulates the inflammatory cascade. A salient feature of diabetes, is endothelial dysfunction which is characterized by a reduction of the bioavailability of vasodilators, particularly nitric oxide (NO). Cellular derangements in diabetes are also related to dysregulation in Ca2+ handling with increased intracellular Ca2+overload, and oxidative stress. PSS increases eNO bioavailability, reduces inflammatory phenotype, decreases intracellular Ca2+ overload, and increases antioxidant capacity. This narrative review and perspective will outline four methods to non-invasively increase PSS; Exercise (the prototype for increasing PSS), Enhanced External Counterpulsation (EECP), Whole Body Vibration (WBV), Passive Simulated Jogging and its predicate device Whole Body Periodic Acceleration, and will discuss current knowledge on their use in diabetes.
Highlights
Diabetes is a worldwide epidemic, with a global prevalence of over 425 million
The direct response of Endothelial derived nitric oxide synthase (eNOS) activation and nitric oxide (NO) production to pulsatile shear stress (PSS) in these experiments and others, have clearly shown that PSS is important for endothelial homeostasis. endothelial derived nitric oxide (eNO) is critical for vasorelaxation, increasing blood flow, and an important signaling molecule that downregulates the inflammatory cascade (Albrecht et al, 2003; Cirino et al, 2003; Kolluru et al, 2010; Forstermann and Sessa, 2012)
This review will focus on four non-pharmacologic methods for sustained shear stress, which increase pulsatile shear stress to the vascular endothelium and have been shown to confer a protective role in diabetes and other diseases; Exercise, External Counterpulsation (EECP), Whole Body Vibration (WBV), and Whole Body Periodic Acceleration (WBPA/pGz), or Passive Jogging Device (JD) Figure 1
Summary
Diabetes is a worldwide epidemic, with a global prevalence of over 425 million. Diabetes accounts for nearly 9.4% of the United States population with an estimated cost of over $300 billion annually (Willey et al, 2018). This review will focus on four non-pharmacologic methods for sustained shear stress, which increase pulsatile shear stress to the vascular endothelium and have been shown to confer a protective role in diabetes and other diseases; Exercise, EECP, WBV, and Whole Body Periodic Acceleration (WBPA/pGz), or Passive Jogging Device (JD) Figure 1. EECP adds additional pulsations to the endothelium, which have been shown to induce production of nitric oxide (Akhtar et al, 2006), improve flow mediated vasodilation (FMD) endothelial function (Shechter et al, 2003; Braith et al, 2010), attenuate proinflammatory signaling pathways (Zhang et al, 2010; Martin and Braith, 2012) and improve quality of life (Jan et al, 2020) amongst others. EECP, enhanced external counterpulsation; WBV, whole body vibration; WBPA, whole body periodic acceleration; JD, passive jogging device; eNO, endothelial derived nitric oxide; OGTT, oral glucose tolerance test; AUC, area under the curve.
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