Cause or Effect?
Microvascular Dysfunction in Insulin-Resistant States
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- adipose tissue
- contrast echocardiography
- insulin resistance
- type 2 diabetes mellitus
See Article by Hu et al
Conventionally, it is understood that the vasculature is one of many tissues that are adversely affected in patients with type 2 diabetes mellitus (T2DM). Accelerated development of arterial atherosclerosis and microvascular dysfunction are 2 of the diabetic complications that cardiovascular clinicians commonly encounter. Microvascular dysfunction, defined as inadequate microvascular response to metabolic demand at rest or during a physiological or metabolic challenge that normally requires a reduction in vascular resistance, occurs as a consequence of multiple pathways that become abnormal in response to obesity, insulin resistance (IR), hyperglycemia, and T2DM. These pathways are diverse and include reduced bioavailability of nitric oxide and other vasodilators (eg, eicosanoids and other arachidonic acid metabolites), increased production or sensitivity to vasoconstrictors, including endothelin or angiotensin-II, heightened response to α-adrenergic signaling, functional abnormalities in cation channels, diffuse glycosylation, and increased reactive oxygen species.1,2 Tissues affected by secondary microvascular dysfunction include the heart, skeletal muscle, adipose tissue, and the kidney.
A somewhat underappreciated concept is that microvascular dysfunction can actually contribute to the pathogenesis of IR and T2DM. Much of research supporting this notion has focused on the microcirculation of skeletal muscle which in humans is a major storage site for glucose. In limb skeletal muscle, insulin produces an augmentation in limb skeletal muscle blood flow in a dose-dependent fashion.3,4 This vascular action of insulin is thought to influence the delivery of glucose, and possibly insulin itself, to muscle and other glucose storage sites.5 The measurement of blood flow alone may not tell the whole story of how vascular responses influence glucose homeostasis. …