Diabetes and cardiovascular disease: pathophysiology of a life-threatening epidemic

Diabetes is associated with the development of premature cardiovascular disease (CVD), which relates to the clustering of risk factors such as dyslipidaemia, hypertension, obesity and hyperglycaemia in the presence of insulin resistance. In addition, diabetes is associated with an inflammatory and pro-thrombotic environment, exacerbating the development of atherothrombosis. Insulin resistance and hyperglycaemia both contribute to the development of endothelial cell dysfunction and increased oxidative stress, culminating in accelerated atherosclerosis. Clot formation and function are also directly affected by insulin resistance and hyperglycaemia, with increased levels of coagulation factors and anti-fibrinolytic proteins and a fibrin network that is more resistant to lysis, coupled with increased platelet activation. It is well recognised that the intensification of glycaemic control leads to a reduction in microvascular complications in type 1 and type 2 diabetes; however, the same is less clear with macrovascular disease. Several randomised studies have attempted to address the effect of short-, medium- and long-term glycaemic control on cardiovascular outcomes, with mixed results. The overall interpretation of these trials suggests that intensive glycaemic control in patients with a relatively short duration of diabetes, without very poor control and with no CVD, might be safe and associated with fewer cardiovascular events. This review will summarise the effects of hyperglycaemia on the development of atherothrombosis and examine key cardiovascular outcome trials following intensive glucose control.