Insulin Resistance and Cardiovascular Disease

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About this Research Topic

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Background

Diabetes affects 425 million individuals worldwide, with numbers projected to increase to >600 million in the next 20 years. Despite advances in therapies, cardiovascular complications remain the main cause of morbidity and mortality in this population. The risk of developing such complications is variable across this highly heterogeneous population and is determined by a range of factors including age, duration of diabetes, glycaemic control, and insulin resistance (IR). In type 1 diabetes (T1D), patients experience insulin deficiency caused by reduced insulin production, whereas in type 2 diabetes (T2D), patients have relative insulin deficiency secondary to IR, usually due to obesity.



In the heart, the major factors contributing to the development of IR are increased oxidative stress, hyperglycemia, and elevated lipid levels. The effects of cardiac IR are further exacerbated through metabolic, endocrine, and cytokine-related defects associated with systemic IR. At the cellular level, IR causes dysregulated calcium handling, mitochondrial dysfunction, and metabolic inflexibility resulting in a range of pathologies that include, but are not limited to, dysregulated myocardial-endothelial interactions, impaired diastolic dysfunction, myocardial cell death, and fibrosis.



Vascular events associated with IR are generally related to an enhanced thrombotic environment. Obstructive blood clots (leading to myocardial infarction, cerebrovascular events, or critical limb ischaemia) result from complex interactions between platelets and haemostatic proteins. In individuals with IR, activation of both the cellular and protein arms of coagulation lead to the formation of altered fibrin networks coupled with hypofibrinolysis, which contributes greatly to adverse clinical outcomes.



In this Research Topic we will present a range of articles (Original research, reviews, mini reviews, and perspectives) that explore and illustrate the key molecular events that underpin IR and its detrimental effects on the cardiovascular system. These articles will highlight the mechanisms by which IR leads to abnormal cardiac functioning, heart failure and vascular disease and describe the methods and cellular/animal models used to study the effects of IR. Finally, these articles will also review current therapeutic strategies for the treatment and management of cardiovascular complications in diabetes and introduce new potential targets and emerging treatments.

Research Topic Research topic image

Keywords: cardiomyopathy, diabetes, diabetic retinopathy, heart failure, hypercoagulation, hyperglycaemia, insulin dynamics, insulin resistance, thrombosis, vascular disease

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