Atherosclerosis: Pathophysiology of insulin resistance, hyperglycemia, hyperlipidemia, and inflammation

作者：Joshua Beverly, Matthew J. Budoff · 发表于：Journal of Diabetes · 年份：2019 · DOI：10.1111/1753-0407.12970 · 被引用次数：227 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Diabetes, Cardiovascular Risks, and Lipoproteins、Lipoproteins and Cardiovascular Health

Atherosclerotic cardiovascular disease (CVD) is on course to surpass infectious diseases as the leading cause of morbidity and mortality worldwide.1 Multiple risk factors are responsible for this trend including the increasing average life expectancy and reducing rates of communicable diseases in addition to potentially modifiable risk factors, such as tobacco use, hypertension, hyperlipidemia, and diabetes mellitus.1 The development of atherosclerosis is driven by multiple factors including hypertension, dyslipidemia, inflammation, insulin resistance, and hyperglycemia. While many techniques are available to accurately measure atherosclerosis (coronary artery calcium scanning, CT angiography, intravascular ultrasound), understanding the pathophysiology of the disease may help drive discovery to ultimately prevent the disease. An important distinction to draw is the role of insulin resistance vs hyperglycemia in the development of atherosclerosis. Although both likely have a synergistic atherogenic effect in the setting of type 2 diabetes, insulin resistance has been shown to have a strong link to CVD, even in the absence of hyperglycemia.2 Insulin resistance promotes a pro-inflammatory state and dyslipidemia in addition to perturbed insulin signaling on important intimal cells (endothelial, vascular smooth muscle cells [SMCs], and macrophages) resulting with advanced plaque progression in the setting of hyperinsulinemia.2 Normal insulin signaling in skeletal muscle starts wi...