Cardiometabolic risk comprises a cluster of traditional and emerging factors that are good indicators of a patient’s overall risk
for type 2 diabetes and cardiovascular disease. The insulin resistance, a key feature common to obesity and type 2 diabetes, is associated
with impaired vascular response and contributes to increased cardiovascular risk. Abnormal vascular insulin signalling induces endothelial
dysfunction, the initial step of atherosclerotic process, characterized by attenuated nitric oxide-mediated vasodilatation and atherogenic
response. Insulin resistance and endothelial dysfunction are two pathological conditions that can co-exist, even if their cause-effect
relationship is not yet clarified. Multiple signaling pathways shared by insulin resistance and endothelial dysfunction include hyperinsulinemia,
glucotoxicity, lipotoxicity, and inflammation. These mechanisms selectively impair PI3K-dependent insulin in vascular endothelium
harming endothelial balance and strengthening the evidence of the close association between metabolic and cardiovascular disease.
The present review analyzes the close relationship between endothelial dysfunction and insulin resistance and explores the common
mechanisms, with clinical considerations and pharmacological strategies.
Keywords: Endothelial dysfunction, insulin resistance, insulin signaling pathways, cardiometabolic risk, cardiovascular disease, type 2 diabetes, glucotoxicity, lipotoxicity, inflammation, hyperinsulinemia
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