Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is associated with injury to the vasculature and microcirculation leading to coronary microvascular dysfunction, permeability changes and cardiac dysfunction. In the setting of cardiopulmonary bypass with cardioplegia, poorly-controlled diabetes is associated with significant changes in endothelium-dependent and independent vascular dysfunction, vascular reactivity, vascular permeability, protein expression, cell death, coronary/peripheral microcirculation and reduced vasomotor tone leading to hypotension and impaired endothelial function. The gene expression profiles after cardiopulmonary bypass with cardioplegic arrest is quantitatively and qualitatively different in patients with diabetes. Gene expression profiling capitalizing on the differences between patients with and without diabetes is a good place to identify potential medical targets.