Cardiovascular risk factors in Type 2 diabetes: the role of hyperglycaemia

Macrovascular complications are the most important causes of morbidity, mor tality and disability in people with Type 2 diabetes mellitus. Although oth er known risk factors for macrovascular disease (e.g, dyslipidaemia, hypert ension, obesity) often co-exist, diabetes itself is an important risk facto r for accelerated development of atherosclerosis. Hyperglycaemia, hyperinsu linaemia and insulin resistance may each play a major role in the onset and development of atherosclerotic disease, which causes arterial wall dysfunc tion, haematological disturbances and lipid abnormalities through two mecha nisms: oxidative stress and nonenzymatic glycation. Hyperglycaemia induces damage to the endothelium through activation of mitogen-activated protein k inase, protein kinase C and transcription factor nuclear factor (NF)-kappa B and through increased levels of pro-adhesion proteins such as intracellul ar adhesion molecule (ICAM)-1. The arterial wall tone is shifted towards va soconstriction by hyperglycaemia, which is also associated with vascular sm ooth muscle cell proliferation and increased intimal wall thickness. Altera tion of the coagulation system towards thrombophilia is observed in Type 2 diabetes and a series of lipid abnormalities that facilitate the developmen t of atherosclerosis is evident. In Type 2 diabetes, undiagnosed disease an d unrecognized postprandial hyperglycaemia are becoming the most relevant i ssues in reducing the risk of vascular complications and cardiovascular mor tality; improved glycaemic control may reduce the incidence of macrovascula r complications.