The role of insulin resistance in the pathogenesis of atherosclerotic cardiovascular disease: an updated review

Abstract

Insulin resistance is the main pathologic mechanism that links the constellation of clinical, metabolic and anthropometric traits with increased risk for cardiovascular disease and type II diabetes mellitus. These traits include hyperinsulinemia, impaired glucose intolerance, endothelial dysfunction, dyslipidemia, hypertension, and generalized and upper body fat redistribution. This cluster is often referred to as insulin resistance syndrome. The progression of insulin resistance to diabetes mellitus parallels the progression of endothelial dysfunction to atherosclerosis leading to cardiovascular disease and its complications. In fact, insulin resistance assessed by homeostasis model assessment (HOMA) has shown to be independently predictive of cardiovascular disease in several studies and one unit increase in insulin resistance is associated with a 5.4% increase in cardiovascular disease risk. This review article addresses the role of insulin resistance as a main causal factor in the development of metabolic syndrome and endothelial dysfunction, and its relationship with cardiovascular disease. In addition to this, we review the type of lifestyle modification and pharmacotherapy that could possibly ameliorate the effect of insulin resistance and reverse the disturbances in insulin, glucose and lipid metabolism.

Contrasting associations of insulin resistance with diabetes, cardiovascular disease and all-cause mortality in the elderly: PROSPER long-term follow-up

“…By contrast, both fasting insulin and HOMA-IR were powerfully associated with risk for developing diabetes within the 3.2 years of intrial follow-up, providing evidence of internal validity. Our results therefore suggest that insulin and insulin resistance are unlikely to be important CVD risk factors in elderly people without diabetes [6,14,15]. This is an important finding given that older people have been relatively poorly represented in studies to date but are an increasingly important group in public health terms.…”

Sex hormone binding globulin gene polymorphisms and metabolic syndrome in postmenopausal Turkish women

“…Low SHBG level is an established biomarker of insulin resistance and hyperinsulinemia [15]. Postmenopausal women with high SHBG levels have reduced risk of atherosclerosis and insulin resistance [16][17][18]. Genetic factors that can contribute to the diminished circulating SHBG levels are important in the onset of insulin resistance and MetS.…”

Physical activity as the main therapeutic tool for metabolic syndrome in childhood

“…37 Insulin resistance and increased insulin levels have been shown in children with obesity, 38 impaired glucose tolerance, 39 hypertension 40 and typical MS dyslipidemia. 41 Interindividual variability in insulin action has a genetic basis for B50%, the remaining 50% being equally explained by differences in the degree of adiposity and level of PF. 37 Recently, the importance of an altered fat partitioning (among visceral and subcutaneous abdominal fat, liver and muscles) on the insulin resistance developing in obese adolescents has also been reported.…”