The dysmetabolic syndrome, insulin resistance and increased cardiovascular (CV) morbidity and mortality in type 2 diabetes:: aetiological factors in the development of CV complications

Insulin resistance often clusters with other cardiovascular risk factors, such as obesity, impaired glucose tolerance (IGT), hypertension, dyslipidaemia and impaired fibrinolysis. Collectively, these endocrine and metabolic disturbances are described as the dysmetabolic syndrome, which is also commonly called the "insulin resistance syndrome", the "metabolic syndrome", or "syndrome X". Insulin resistance, working in concert with the other components of the dysmetabolic syndrome, induces deleterious changes to the vascular endothelium and lipid profiles that directly and indirectly promote the progression of atherosclerosis. Insulin resistance in adipocytes, leading to decreased suppression of lipolysis by insulin, may be especially important in this regard. Reduced suppression of lipolysis by insulin in obese subjects is associated with increased levels of fatty acids that damage the arterial wall and promote atherosclerosis. The lipid profiles of insulin-resistant subjects are often characterised by the appearance of hypertriglyceridaemia and small, dense LDL-cholesterol, together with low HDL-cholesterol. In addition, adipocytes are highly active endocrine organs and secrete a range of substances that reduce insulin sensitivity further. The net result of these derangements is a vicious circle, wherein the development of insulin resistance is strongly associated with atherogenic lipid profiles and endothelial dysfunction which, in turn, exacerbates insulin resistance. The consequences for the individual with dysmetabolic syndrome include an increased risk of cardiovascular disease of up to 4-fold compared with subjects without the dysmetabolic syndrome.