Despite considerable progress in the management of major risk factors over recent decades, cardiovascular diseases (CVD) attributable to atherosclerosis are still a predominant cause of death worldwide. This is due, in large part, to the expansion of risk factors related to obesity such as insulin resistance and diabetes [1]. In fact, the risk of developing CVD in adults with diabetes is two to four times higher than in those without diabetes. Moreover, it is well established that insulin resistance and hyperglycemia promote atherosclerosis, leading to coronary artery disease. Yet the underlying mechanisms linking diabetes and atherosclerosis are still not completely understood. To overcome this lack of understanding, numerous studies have been conducted, using mouse models with targeted deletion in intimal cells, to evaluate the impact of impaired insulin signaling at the level of the arterial wall on atherosclerosis development and progression [2]. Taken together, this work highlights the critical consequences of altered insulin signaling, in both macrophages and endothelial cells, in atherogenesis and the formation of advanced plaques. In humans, comparative analyses of atherosclerotic plaques from diabetic and non-diabetic individuals have revealed some important differences in the quality and composition of plaques between these groups. Lesions from diabetic patients are characterized by a larger necrotic core, increased inflammation, neovascularization, intra-plaque hemorrhage, and calcification [3], [4], [5], [6] and [7]. Higher macrophage and T-cell content, along with increased proportions of apoptotic macrophages and smooth muscle cells, may contribute to this larger necrotic area [4] and [8]. When combined with the increased prevalence of thin-cap fibroatheroma and fibrocalcific atheroma, observed using Virtual Histology intravascular ultrasound in vessels of diabetic patients [5], these alterations of plaque morphology may explain the higher risk of acute coronary syndrome in diabetic patients. Indeed, coronary lesions of patients with diabetes mellitus are more vulnerable to rupture and subsequent thrombosis [3] and [6].