Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes - ABSTRACT: Type 2 diabetes (T2D) in youth reduces quality and years of life. Disparities in T2D emerge early in life and disproportionately impact low-income and minority youth. T2D is the result of complex processes involving biological susceptibility and interdependent social, behavioral, and environmental factors that represent the root causes of disparities. Obesity, insulin resistance and pancreatic β-cell dysfunction have been the focus of many clinical studies aimed at understanding the pathophysiology of T2D in youth. However, multiple factors directly and indirectly contribute to risk including unhealthy behaviors, puberty, genetic predisposition, and epigenetic modulation. These additional factors are influenced by the social and environmental context that must but considered to advance our understanding of T2D in high-risk populations. Our transdisciplinary team has extensive experience understanding, preventing, and managing T2D among vulnerable and underrepresented youth. For over a decade, our research has been guided by a Community Advisory Board that has informed multiple NIH-funded studies focused on T2D in vulnerable populations. Our overall approach to T2D research is framed within an Expanded Ecodevelopmental Model that considers cultural, environmental, and social contexts that influence individual health behaviors and health outcomes during critical life periods. We will apply this model and leverage high-volume pediatric endocrine practice situated within one of the nation’s largest integrated pediatric healthcare systems to recruit a diverse sample of youth with obesity and prediabetes. To further support this work, we have developed a robust community engagement strategy to ensure that the research extends the available science AND advances towards health equity in the local community. Our transdisciplinary team is well-suited to contribute to a national consortium that identifies high-risk youth, understands the pathophysiology of T2D, and ultimately improves the health of this population. With this context, we propose the following Specific Aims: Specific Aim 1: Enroll, phenotype, and prospectively follow an ethnically diverse cohort of 6000 (400/site) children ages 8-14 with obesity and prediabetes. Specific Aim 2: Integrate free living assessments of glycemia and health behaviors. Specific Aim 3: Document family, social and environmental conditions that contribute to T2D risk. Specific Aim 4: Collect and bank fasting blood samples to support genomic and metabolomic analyses using validation and discovery approaches. Specific Aim 5: Examine the individual and potential interactive effects of biological, behavioral, and social determinants of T2D risk.
