The effect of glycemic control on the incidence of macrovascular complications of type 2 diabetes.

Of all the complications of diabetes mellitus, macrovascular complications, ie, large-vessel atherosclerosis, account for the largest share of morbidity, mortality, and health care expenditures. Whereas there is now highly persuasive evidence that glycemic control reduces the risk of microvascular complications in type 1 diabetes, and probably in type 2 diabetes as well, such evidence is unavailable for macrovascular complications. Prospective epidemiologic studies, however, indicate that poor glycemic control enhances cardiovascular risk, and a number of biochemical mechanisms have been advanced to explain this phenomenon. However, data from animal studies, in vitro studies, and prospective epidemiologic studies suggest that endogenous insulin or insulin resistance may be atherogenic. Thus, a dilemma exists for insulin treatment, although the weight of evidence still favors its aggressive use. For persons whose glycemia can be adequately controlled with oral agents, the use of agents such as metformin and troglitazone--which do not raise, and may even lower, insulin concentrations--may offer an advantage. Definitive clinical trials on the benefits and risks of insulin therapy related to macrovascular complications are lacking and urgently needed.