The present invention relates to methodology for preventing increased cardiovascular disease in subjects with diabetes mellitus. The methods include the use of compounds to inhibit activation of the extracellular response kinase pathway, activate 5′ adenosine monophosphate protein kinase, and inhibit microRNA-221 and microRNA-222 for the purpose of reducing microRNA-221 and -222 levels in the vasculature. Reduction of microRNA-221 and -222 in the vasculature of diabetic patients restores normal levels of intimal thickening and enhances the effectiveness of the standard of care in diabetic subjects.
