Epicardial Adipose Tissue and Cardiometabolic Risk Factors in Youth-Onset Type 2 Diabetes Undergoing Bariatric Surgery - 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.
