Insulin resistance is considered to be the hallmark of the pathophysiology of type 2 diabetes and metabolic syndrome, and it has been shown to predict the development of cardiovascular diseases.
1 In order to maintain cardiac contractility and the circulation of blood and oxygen to peripheral organs, the heart needs more energy than any other organ. Fatty acids are the main source of energy in an intact heart, and under stress or pathological conditions the myocardium also utilizes glucose to compensate for energy deficiencies. Insulin signaling may directly control cardiac metabolism; however, its main role may be the regulation of substrate delivery from the periphery to the heart.
2 In generalized insulin resistance, insulin-mediated glucose transport in cardiac muscle is impaired and associated with the development of heart failure unrelated to myocardial ischemia and hypertension.
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4 Many basic studies have underscored the biphasic changes of insulin signaling in the myocardium to systemic metabolic alterations in the evolution of heart failure. In early adaptation of the heart to systemic resistance, the expression of glucose transporter type 4 (GLUT4) can be repressed; however proximal insulin signaling to phosphatidylinositol-3-kinase and protein kinase B may remain intact accompanied by left ventricle (LV) remodeling. However, insulin signaling pathways can become desensitized over time, leading to cardiac decompensation via various mechanisms.
5 Metabolic imaging with
18F-fluorodeoxyglucose (FDG) PET/CT has been widely used to both assess myocardial viability and also evaluate exogenous glucose utilization rate. Several clinical and animal studies have observed myocardial glucometabolic derangements in patients with diabetes mellitus and heart failure using dynamic imaging, although the causal relationship could not be clearly verified. In addition, myocardial glucose metabolism can be altered by blood substrate levels and some medications for hyperlipidemia and diabetes.
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