Type 2 Diabetic Individuals Have Impaired Leg Blood Flow Responses to Exercise

Abstract

OBJECTIVE -Diabetic individuals have impaired endothelium-dependent forearm vasodilatory responses to ischemia, acetylcholine, and other endothelium-dependent agonists. The functional significance of impaired endothelium-dependent dilation in diabetic individuals is uncertain but is most likely to be manifest during leg muscle exercise and may have relevance to peripheral vascular disease and leg ischemia, which is prevalent in diabetic individuals. The current study aimed to determine the relationship between leg blood flow (LBF) responses to endothelium-dependent vasodilation and dynamic large muscle exercise. RESEARCH DESIGN AND METHODS -LBF responses (thermodilution)to intrafemoral arterial infusions of an endothelium-dependent (acetylcholine) and endotheliumindependent (sodium nitroprusside) vasodilator and a standardized 25-min cycling bout at 60% VO 2peak were compared in nine male type 2 diabetic subjects and nine age-, sex-, VO 2peak -, and weight-matched control subjects.RESULTS -LBF responses to acetylcholine and exercise but not sodium nitroprusside were significantly (P Ͻ 0.05) attenuated in patients with diabetes compared with healthy control subjects. The percentage increase in LBF in response to exercise and acetylcholine were significantly correlated (r ϭ 0.54, P ϭ 0.02). Furthermore, resting plasma glucose was significantly related to the LBF response to exercise (r ϭ Ϫ0.66, P ϭ 0.003) independently of insulin, HbA 1c , lipids, BMI, and blood pressure.CONCLUSIONS -The increase in LBF during exercise is substantially attenuated in type 2 diabetic compared with matched control subjects. Impaired endothelium-dependent vasodilation secondary to elevated plasma glucose may underlie this observation. This mechanism may be of importance in determining the leg ischemic threshold in diabetic individuals with peripheral vascular disease. Diabetes Care 26:899 -904, 2003

Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome

“…2). Similar results were also found in patients with type 2 diabetes (14). Because previous studies have supported a critical role of prostaglandin(s) in mediating functional vasodilation (10,19,20,24,30), it is possible that the impaired functional vasodilation in metabolic syndrome may be due to altered AA metabolism.…”

“…For example, SNP-induced dilation of isolated cerebral arteries was similar between 17-wk-old LZRs and OZRs (25). SNP-induced vasodilation was similar to controls for individuals with type 2 diabetes, although both ACh-induced and functional vasodilation were blunted (14). Previous studies have suggested that NO may not be important in mediating functional hyperemia (2,27,28,31).…”

“…However, in patients and animals with metabolic syndrome, endothelial dysfunction may occur early in the pathology of this syndrome (4), possibly contributing to the impaired functional hyperemia seen in metabolic syndrome. For example, patients with type 2 diabetes exhibit an impaired endothelial-dependent vasodilatory response to ACh and a significant impairment of the functional hyperemic response to leg cycle ergometer exercise (14). Our laboratory and others (8,32) have demonstrated that the obese Zucker rat (OZR), a model of metabolic syndrome, have both an attenuated functional and ACh-induced vasodilation in skeletal muscle arterioles.…”

Systolic and Diastolic Abnormalities Reduce the Cardiac Response to Exercise in Adolescents With Type 2 Diabetes

“…Instead, the T2DM subjects achieved a smaller increase in cardiac output, despite having higher left ventricular stroke work during exercise. Vascular function is impaired in adults with T2DM (35,36) and ObeseND adolescents (37). Therefore, it appears that attenuated peripheral vasodilation during exercise, combined with a limited ability to increase cardiac contractility may have contributed to a smaller increase in cardiac output during steady-state exercise.…”

Microvascular oxygen partial pressure during hyperbaric oxygen in diabetic rat skeletal muscle

“…Type 2 diabetes also presents a severe impairment of arterial (19,34) and microcirculatory (27, 28) hemodynamics in skeletal muscle at rest and during exercise. Key contributors to this condition are thought to include upregulation of endothelin-1 (37), prostaglandin (1), and myogenic (43) vasoconstrictor pathways combined with downregulation of vasodilatory endothelial function and nitric oxide bioavailability (17,24,48). Given the above, it is not surprising that the dynamics of Q O 2 , following exercise onset, for example, may be deficient as evidenced by the aberrant Pmv O 2 profile to muscle contractions, which reflects an imbalance between Q O 2 and V O 2 responses [type I (3); type 2 (28)].…”