Association between insulin resistance and the development of cardiovascular disease

Abstract

For many years, cardiovascular disease (CVD) has been the leading cause of death around the world. Often associated with CVD are comorbidities such as obesity, abnormal lipid profiles and insulin resistance. Insulin is a key hormone that functions as a regulator of cellular metabolism in many tissues in the human body. Insulin resistance is defined as a decrease in tissue response to insulin stimulation thus insulin resistance is characterized by defects in uptake and oxidation of glucose, a decrease in glycogen synthesis, and, to a lesser extent, the ability to suppress lipid oxidation. Literature widely suggests that free fatty acids are the predominant substrate used in the adult myocardium for ATP production, however, the cardiac metabolic network is highly flexible and can use other substrates, such as glucose, lactate or amino acids. During insulin resistance, several metabolic alterations induce the development of cardiovascular disease. For instance, insulin resistance can induce an imbalance in glucose metabolism that generates chronic hyperglycemia, which in turn triggers oxidative stress and causes an inflammatory response that leads to cell damage. Insulin resistance can also alter systemic lipid metabolism which then leads to the development of dyslipidemia and the well-known lipid triad: (1) high levels of plasma triglycerides, (2) low levels of high-density lipoprotein, and (3) the appearance of small dense low-density lipoproteins. This triad, along with endothelial dysfunction, which can also be induced by aberrant insulin signaling, contribute to atherosclerotic plaque formation. Regarding the systemic consequences associated with insulin resistance and the metabolic cardiac alterations, it can be concluded that insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to the myocardium. The aim of this review is to discuss the mechanisms associated with insulin resistance and the development of CVD. New therapies focused on decreasing insulin resistance may contribute to a decrease in both CVD and atherosclerotic plaque generation.

Association of increased hepatic insulin clearance and change in serum triglycerides or β‐hydroxybutyrate concentration via the sodium/glucose‐cotransporter 2 inhibitor tofogliflozin

“…Insulin resistance caused by weight gain and visceral fat accumulation may lead to hyperinsulinaemia, which might prompt not only further weight gain but also cardiometabolic disorders associated with the risk of cardiovascular disease . A decline in hepatic insulin clearance is one of the causes of hyperinsulinaemia .…”

The immune-opioid axis in prediabetes: prediction of prediabetes with insulin resistance by plasma interleukin-10 and Endomorphin-2 to kappa-opioid receptors ratio

“…IR can also alter systemic lipid metabolism, leading to the generation of dyslipidemia. Along with endothelial dysfunction, which can also be created by an abnormality of insulin signaling, IR contributes to the atherosclerotic plaque production [36].…”

“…IR in the myocardium produces damage by signal transduction modification, impaired regulation of substrate metabolism, and variation in the delivery of substrates to the myocardium [36].…”

Ketogenic diets and protective mechanisms in epilepsy, metabolic disorders, cancer, neuronal loss, and muscle and nerve degeneration

“…Type 2 diabetes mellitus (T2DM) manifests characteristics of insulin resistance and hyperinsulinemia, and hence insulin therapy that often associates with cardiovascular damage and coronary artery calcification poses several adverse effects (Ormazabal et al, 2018). As an alternative, randomized clinical studies on dietary carbohydrate constraint or KD showed an improved glucose metabolism and glycemic control, reducing the use of antiglycemic medication (Westman, Tondt, Maguire, & Yancy, 2018).…”