The study of 201 type 2 diabetics and 65 nondiabetics with CAD was conducted by Dr. Dominick Angiolillo of the University of Florida at Jacksonville and colleagues at San Carlos University Hospital in Madrid, Spain. Among the type 2 diabetics, 68 were on insulin and 133 were on other anti-diabetic therapies. All patients were on steady doses of aspirin and clopidogrel.

Platelet aggregation is mediated through the platelet P2Y receptor, the researchers explain in the July 18th issue of the Journal of the American College of Cardiology, and insulin inhibits platelet aggregation by suppressing the P2Y pathway. However, type 2 diabetics, in whom insulin resistance is a problem, have an up-regulation of the P2Y pathway, which in turn increases platelet aggregability.

The investigators assessed platelet aggregation in diabetics and controls using agonists and nonagonists specific to the PY2 pathway.

The diabetics as a group had increased platelet aggregation and increased shear-induced platelet function. Platelet dysfunction was independent of glycemic control and inflammatory status.

Platelet aggregation was higher among those on insulin than those on other therapies after P2Y pathway-specific stimuli. Platelet function profiles were similar in both groups of diabetics using assays nonspecific to the P2Y pathway.

Dr. Angiolillo and colleagues note, "The seminal findings of our present functional study may provide a mechanistic explanation to the higher ischemic risk observed in type 2 diabetic patients, especially (those on insulin therapy), within larger-scale clinical studies."

J Am Coll Cardiol 2006;48:298-04.