Pancreatic fat and volume and childhood metabolic health

About This Grant

PROJECT SUMMARY/ABSTRACT The rise of type 2 diabetes (T2D) in U.S. youth is an alarming public health issue. Although obesity is a strong risk factor for pediatric T2D, at the same time, only a subset of youth with obesity develops T2D, suggesting disease pathogenesis is driven by factors beyond total adiposity. It is well-established that altered body fat trafficking into abdominal and hepatic fats is strongly correlated with metabolic dysfunction in youth, independent of obesity. Recently, pancreatic traits assessed by imaging, particularly pancreatic fat and volume, have also emerged as potential risk factors for dysglycemia in youth. However, research examining the metabolic effects of these traits in youth has been limited to smaller cross-sectional studies, primarily conducted in clinical populations (i.e., children with existing obesity, fatty liver, or dysglycemia). Also, few, if any, human studies have explored the influence of the early nutritional environment on these pancreatic traits. In the proposed K99/R00 award, we will address these knowledge gaps by leveraging data from the Healthy Start Study, a longitudinal, pre-birth, cohort study in Colorado that has comprehensively characterized ~1,400 mother-child pairs since pregnancy. The applicant, Dr. Catherine Cohen, PhD, RDN, will add quantitative magnetic resonance imaging (MRI) sequences to scans performed at the next wave of visits when offspring are in adolescence (10-15 years) to measure pancreatic fat and volume. This data will then be used to pursue the following specific aims: Aim 1. Assess pancreatic fat and volume in a general risk cohort of adolescents and examine interindividual variation in relation to child characteristics and adiposity measures (K99). Aim 2. Test prospective associations of early nutrition/growth with pancreatic fat and volume in adolescence (K99/R00). Aim 3. Examine associations of pancreatic fat and volume trajectories across adolescence with trajectories of glucose-insulin markers across adolescence, and the role of pancreatic traits in mediating associations of early nutrition and growth with glycemic markers (R00).Taken together, the findings of this proposal will improve knowledge of the role of pancreatic traits as risk markers for early onset dysglycemia during puberty and generate insights that will enhance our ability to design and target T2D prevention strategies more effectively. The proposed training goals for the K99 phase will complement this research and focus on gaining: (1) experience applying lifecourse epidemiology concepts, (2) expertise in assessing body composition, especially adiposity measures, and (3) knowledge of pediatric T2D pathophysiology and dynamic glucose-insulin assessments, and will be achieved through individual mentorship, practical experiences, and didactic training, and supplemented with opportunities to expand professional development skills. Collectively, the proposed research and training activities will strategically equip the applicant with the knowledge/skills needed to transition from mentored (K99) phase to independent (R00) phase.