Determination of the Genetic Contribution to Glycemic Control and CAD Outcomes in Patients with DM2 and CAD 

Sharon Cresci, M.D.


Project Overview: 
Diabetes mellitus (DM) currently affects more than 220 million people worldwide and its prevalence is increasing. Among persons with DM, complications of accelerated atherosclerosis, particularly acute coronary events, are the principal causes of death. To date, few studies have examined the hypothesis that genetic variation may account for variable responses to treatment and variable clinical outcomes among patients with DM and coronary artery disease (CAD).

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial is a multicenter trial examining the effects of different approaches to treatment of CAD and DM on long-term outcomes in patients with type 2 DM. This study will use genetic samples from BARI 2D trial participants to examine the PPARalpha gene to determine if specific gene sequence differences can predict poor outcomes and better or worse patient responses to certain treatments for DM or CVD.



Final Report Abstract:
Diabetes mellitus (DM) currently affects more than 220 million people worldwide and its prevalence is increasing. Among persons with DM, complications of accelerated atherosclerosis, particularly acute coronary events, are the principal cause of death. To date, few studies have examined the hypothesis that genetic variation may account for variable responses to treatment and variable clinical outcomes among patients with DM and coronary artery disease (CAD).

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) is a multicenter trial examining the effects of different approaches to treatment of CAD and DM on long-term outcomes in patients with type 2 DM. Using a custom PPAR-pathway gene SNP microarray containing 3,351 single nucleotide polymorphisms (SNPs) in 223 PPAR-pathway genes, we investigated genetic associations of PPAR-pathway genes with extent of CAD among patients with DM in the BARI 2D trial. We found a specific variant in a PPAR-pathway gene that was associated with the extent of CAD in BARI 2D and validated this finding in two independent cohorts. This is the first report of a genetic variant that correlates with the extent of atherosclerosis in patients with diabetes. The physiologic pathways affected by this genetic variant may provide novel targets for further investigation and therapeutic intervention to address the accelerated rate of progression and the high risk of adverse events associated with CAD in patients with DM.  Read the full Final Report.