Insulin resistance and cardiovascular disease

Abstract

Insulin resistance (IR) and cardiovascular disease (CVD) represent two universal public health hazards, especially in today's Western societies. A causal-effect relationship has been established that links IR with CVD. The mediating mechanisms are perplexing, under ongoing, rigorous investigation and remain to be fully elucidated. IR is a condition encompassing hyperglycemia and compensatory hyperinsulinemia. It occurs when insulin is not capable of exerting its maximum effects on target tissues, including skeletal muscles, liver and adipose tissue. This alteration of insulin signaling pathways results in the development of cardiometabolic disorders, including obesity, dyslipidemia, low-grade inflammation, endothelial dysfunction and hypertension, all of which are predisposing factors for atherosclerosis and CVD. The management of IR can be achieved through dietary modifications, the inclusion of regular exercise routines in everyday life, pharmacological agents and other interventions tailored to each individual patient's needs. It is important to underline though that, although various antidiabetic drugs that may improve IR are available, no medications are as yet specifically approved for the treatment of IR. This narrative review will focus on the current scientific and clinical evidence pertaining to IR, the mechanisms connecting IR with CVD, as well as plausible strategies for a holistic, personalized approach for IR management.

Keywords: Insulin; cardiovascular disease; dyslipidemia; endothelial dysfunction; hypertension; inflammation; insulin resistance; oxidative stress.

Figure 1.

Schematic depiction of the pathophysiological factors linking insulin resistance (IR) with cardiovascular disease (CVD). FFA, free fatty acids; LDL-C, low-density lipoprotein cholesterol; sdLDL-C, small dense LDL-C; TGs, triglycerides; HDL-C, high-density lipoprotein cholesterol; ROS, reactive oxygen species; oxLDL-C, oxidized LDL-C; AGEs, advanced glycation end-products; NO, nitric oxide; RAAS, renin–angiotensin–aldosterone system; ET-1, endothelin-1.