Diabetes and cardiovascular outcomes: finding the silver lining

Type 2 diabetes mellitus and cardiovascular disease create a pernicious synergism that now threatens the public health in both developed and developing countries. As such, there has been a concerted therapeutic effort to mitigate the effects of hyperglycemia on adverse cardiovascular outcomes. Despite compelling epidemiological evidence linking diabetes to cardiovascular disease and mechanistic evidence linking hyperglycemia to cardiomyocyte and endothelial cell toxicity, clinical trials designed to examine the effects of tight glycemic control on CV outcomes have been disappointing. The apparent paradox requires a re-examination of the premise as well as consideration of new therapeutic approaches beyond tight glycemic control alone. In this review, we will review the evidence that links diabetes to adverse cardiovascular outcomes and will examine the mechanistic evidence whereby hyperglycemia causes cellular damage in experimental models. We will extrapolate from information gleaned from recent clinical trials and discuss a new therapeutic approach that embraces glycemic control, but with less collateral side effects and perhaps by mechanisms that are also cardio-protective.