PROJECT SUMMARY/ABSTRACT
The prevalence of adolescent obesity continues to rise, with parallel increases in obesity-related comorbidities
such as cardiovascular disease (CVD) and type 2 diabetes (T2D). Our lab has demonstrated that youth onset
T2D (Y-T2D) appears to be a more aggressive disease than in adults, thus dedicated studies investigating
comorbidities of obesity such as CVD and T2D are critical. Epicardial adipose tissue (EAT) is a visceral fat
depot that has anatomical proximity to the coronary arteries surrounding the heart and has been suggested as
an independent cardiometabolic risk factor in adults. EAT is a highly active metabolic tissue that secretes pro-
inflammatory factors and therefore is reasonable to expect EAT to have deleterious consequences in cardiac
health. However, the relationship between EAT and CVD in adolescents is less studied. Further, measurement
of EAT has been commonly performed using echocardiogram, which can result in poor image quality when
compared to gold standard MRI, or computed tomography which includes radiation risk. Thus, it is critical to
address early indicators of CVD such as EAT in adolescents with obesity and T2D. We propose to use novel
cardiac MRI methods to assess cardiac structure and function, including EAT. Further, it is important to study
the impact of diabetes treatments on cardiometabolic risk factors. Specifically, metabolic and bariatric surgery
(MBS) is now under investigation in youth with severe comorbidities of obesity and appears to elicit significant
weight loss, however there is less data on its impact on overall cardiovascular health in adolescents. MBS is
also being studied for its weight loss independent effect on metabolism and health, including on the incretin
hormone glucagon-like peptide-1 (GLP-1) which has recently been shown to improve glycemic control and
even facilitate weight loss. Therefore, the goal of this proposal is to investigate the potential independent
relationship between EAT and cardiometabolic health in Y-T2D and explore changes in EAT as a potential
mediator of changes in cardiometabolic health in response to MBS. To address this goal, the first aim of this
proposal will be to determine if baseline MRI-assessed EAT in Y-T2D correlates with cardiometabolic health,
independent of BMI. Adolescents undergoing MRI of the heart and aorta will have EAT volume measured and
related to cardiometabolic health. The second aim of this proposal is to determine the impact of MBS on EAT
volume in adolescents with T2D and if improvements are independent of weight loss, with the potential
improvements mediated through GLP-1 secretion. To summarize, this dedicated study in adolescents with
severe obesity and Y-T2D will add to the current gap in knowledge as there are no publications to-date
examining the effect of MBS on EAT, nor on cardiac or vascular structure or function, nor on the relationship
between EAT and cardiometabolic health in Y-T2D.