Residual vascular risk in diabetes - Will the SPPARM alpha concept hold the key?

Blood pressure, low-density lipoprotein cholesterol (LDL-C), glycemia (for microvascular disease) represent the triumvirate of targets for managing vascular risk in type 2 diabetes. Novel treatments that substantially lower LDL-C levels, or that improve glucose control, can provide additional vascular risk reduction. Despite these advances in best care, however, an unacceptably high residual cardiovascular risk persists. Therefore, therapeutic interventions aimed at additional targets are needed. A key contender to address the enigma of residual vascular risk is the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa). PPARa, which is predominantly expressed in metabolically active tissues, pivotally regulates key metabolic and inflammatory pathways. Critical to this role is the ability of PPARa to exert either positive or negative control over the expression of genes involved in fatty acid oxidation, lipoprotein metabolism, and inflammation.