ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES (ACCORD), THE ACTION IN DIABETES AND
VASCULAR DISEASE:
Preterax and
Diamicron Modified Release Controlled Evaluation and the Veterans Affairs Diabetes Trial were designed to study whether older patients with
type 2 diabetes mellitus could reduce the risk of
heart attacks and
stroke and thereby prolong their lives by maintaining their
blood glucose levels at near-healthy levels but failed to demonstrate the hoped-for benefit. Why the trials failed, though, and why ACCORD saw significantly more deaths due to increased rates of cardiovascular events in the intensive
therapy arm of the study are not clear. These data have now been confirmed by the results of the recently concluded NICE-
SUGAR Study which again revealed that intensive
glucose control increased mortality among adults in intensive care units. I propose that the negative results noted in these trials are due to altered brain
serotonin concentrations and autonomic dysregulation in addition to the low-grade systemic
inflammation, decreased endothelial
nitric oxide and enhanced
free radical generation, diminished
anti-oxidant defenses and altered metabolism of
essential fatty acids present in patients with
type 2 diabetes.