Immune regulators of inflammation in obesity-associated type 2 diabetes and coronary artery disease

Abstract

Purpose To summarize current work identifying inflammatory components that underlie associations between obesity-associated type 2 diabetes (T2D) and coronary artery disease (CAD). Recent findings Recent studies implicate immune cells as drivers of pathogenic inflammation in human T2D. Inflammatory lymphocytes characterize unhealthy adipose tissue (AT), but regional adipose volume, primarily visceral and pericardial fat; also predict severity and risk for obesity-associated CAD. Having a greater understanding of shared characteristics between inflammatory cells from different AT depots and a more accessible tissue such as blood will facilitate progress towards clinical translation of our appreciation of obesity as an inflammatory disease. Summary Obesity predisposes inflammation and metabolic dysfunction through multiple mechanisms, but these mechanisms remain understudied in humans. Studies of obese subjects have identified disproportionate impacts of specific T cell subsets in metabolic diseases like T2D. Based on demonstration that AT inflammation is depot-specific, analysis of adiposity by waist-to-hip ratio or magnetic resonance imaging (MRI) will increase interpretive value of lymphocyte-focused studies and aid clinicians in determining which obese individuals are at highest risk for CAD. New tools to combat obesity-associated CAD and other co-morbidities will stem from identification of immune cell-mediated inflammatory networks that are amenable to pharmacological interventions.

Epicardial adipose tissue: at the heart of the obesity complications

“…In line with other observations [16,36], this suggests that the contribution of EAT to the coronary atherosclerotic burden is more relevant in non-obese than in obese patients and raises the issue of whether obesity may conceal the pathogenetic effects of EAT on CAD progression. Alternatively, it can be theorized that the factors mediating the association between EAT and CAD might change when obesity develops [38].…”

Thermogenic potential and physiological relevance of human epicardial adipose tissue

“…Alternatively, it has been postulated that the mechanisms underlying the association between epicardial fat and development of CAD might be different for lean and obese individuals. 31 …”

“…4,10 In fact, in comparison with the Framingham risk score (where smoking and type 2 diabetes mellitus only account for 1.6-and 3-fold risk of having CAD, respectively), pericardial fat volume was identified as the strongest predictor of developing CAD (odds ratio of 4.1). 30,31 In addition, a case-control study identified pericardial fat volume to be a strong predicator of myocardial ischemia in patients without CAD. 32 The question of whether such predictive capabilities can be attributed specifically to epicardial fat has been addressed by recent studies such as the Heinz Nixdorf Recall study, where epicardial fat volume was significantly associated with coronary events over the course of 8 years, even after adjusting for traditional cardiovascular risk factors.…”

The Pediatric Obesity Epidemic and the Role of the Corporation: Why Work Conditions and Faith in Meritocracy Matter

“…Obesity is an alarming epidemic because of its comorbidities, which include diabetes, cardiovascular disease [4], and based on new evidence, increased risk of some forms of cancer [5,6]. Obesity-driven diabetes, or Type 2 diabetes, was previously only a problem for adults and was termed "adult-onset" diabetes, to distinguish it from "childhood" diabetes, or Type 1 diabetes, which is primarily immunological in origin.…”