The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years. Cardiac function is compromised in diabetes. Diabetic patients manifest accelerated atherosclerosis in coronary arteries. These data are confirmed in diabetic animal models, where lesions of small coronary arteries have been described. These concepts are epitomized in the classic microvascular complications of diabetes, i.e. blindness, kidney failure and distal dry gangrene. Most importantly, accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility. This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes, and assesses the current state of knowledge regarding the triggers for inflammation in this disease. We evaluate the roles of hyperglycemia, oxidative stress, polyol pathway, protein kinase C, advanced glycation end products, insulin resistance, peroxisome proliferator-activated receptor-γ, inflammation, and diabetic cardiomyopathy as a "stem cell disease". Furthermore, we discuss the mechanisms responsible for impaired coronary arteriole function. Finally, we consider how new insights in diabetes may provide innovative therapeutic strategies.

In a murine model of T2DM, dendritic cells accumulated predominantly in PVAT, as opposed to the vessel wall, per se. Accumulation of dendritic cells in PVAT was associated with overproduction of pro-inflammatory cytokines, which contributed to an impaired ability of PVAT to augment vasorelaxation and exert anti-contractile activity in T2DM.

Type 2 diabetes is associated with chronic systemic inflammation and the recruitment of immune cells. In this study, we postulated that CD11c positive cells, a specific subset of lymphocytes, are increasingly expressed with age in perivascular adipose tissues from diabetic mice. Homozygous Type 2 diabetic (db/db) and heterozygous control (DbHET) mice from the same strain were purchased from Jackson Laboratory, and divided into four age groups: 6‐10, 12‐16, 18‐22, and greater than 24 weeks. Epididymal (EAT), mesenteric (MAT), pericardial (PCAT), and periaortic (PAAT) adipose tissues were collected from the db/db and DbHET mice along with spleen, thoracic aortas (TA), mesenteric (MA), and left anterior descending coronary (LAD) arteries. All samples were used to detect CD11c m RNA level using quantitative real‐time PCR. Our data show an age‐dependent increase in CD11c expression of EAT, MAT, PCAT and PAAT adipose tissues from db/db mice. In contrast, CD11c expression remained constant among all four age groups of DbHET mice. Within each age group, higher adipose tissue CD11c levels were observed in db/db mice, compared to those of the DbHET mice. No significant changes of CD11c expression were detected in spleen, TA, MA or LAD. Overall, our data support the conclusion that in a mouse model of Type 2 diabetes, CD11c positive cells accumulate in a duration of diabetes‐dependent manner in the perivascular adipose tissues, rather than in the vascular wall. The impact of these cells on vascular function therefore likely occurs through paracrine regulated mechanisms. Grant Funding Source: NIH HL085119