Project Summary / Abstract
Youth onset type 2 diabetes (YOT2D) is increasing in prevalence by approximately 5% per year, and
disproportionately impacts youth from many minority race/ethnic groups. YOT2D is a rapidly progressive
disease in young adults leading to many life-long health complications resulting in increased morbidity and
mortality. Research shows a key marker in the progression of YOT2D is failure of the ß cells. To date,
identifying predictors of ß cell failure and thus the progression to YOT2D have not been elucidated making
early intervention and prevention impossible. The goal of the present proposal, Identifying Metabolic and
Psychosocial Antecedents and Characteristics of youth-onset Type 2 diabetes (IMPACT DM), is to develop a
comprehensive prediction model that will identify youth at the highest risk of developing YOT2D setting the
stage to implement prevention strategies preserving ß cell function. The overarching hypothesis is that a
combination of physiologic and psychosocial factors, specifically puberty, in utero exposures, and psychosocial
stresses, are major drivers of the development of YOT2D. The cohort will include those at the highest risk of
developing YOT2D in order to deeply phenotype them physically, metabolically, and psychosocially all in an
effort to develop a comprehensive prediction model. Aim 1 will examine glucose homeostasis and changes in
glycemia over time using conventional OGTT methods as well as free-living continuous glucose monitoring
(CGM). These measures will then be used to examine their relationship to ß cell function which is the driver of
diabetes progression identifying key glycemic features that predict YOT2D. Aim 2 will identify physiologic and
psychosocial variables such as hormones, cardiometabolic health, energy expenditure, adverse childhood
events (ACEs), and in utero exposures that predict ß cell function and thus YOT2D. Additional novel predictors
of YOT2D will be examined in Aim 3, specifically focusing on metabolomic profiles, microbiome, and circulating
miRNA. Using these novel variables as well as the glycemic, physiologic, and psychosocial variables identified
in the previous aims, a comprehensive model to predict YOT2D will be developed. The University of Oklahoma
Health Sciences Center (OUHSC) is exceptionally well-suited for this study because of the population served
(8th in the nation for the highest rates of childhood obesity and substantial Hispanic and Native American
populations), and established partnerships. In the TODAY trial, the Oklahoma clinical center recruited and
retained more participants than any of the other 14 study sites. Overall this proposal will lead to the
identification of metabolic and psychosocial antecedents and characteristics that predict the clinical
progression of YOT2D. Also, it would identify factors impacting ß cell function leading to the development
interventions to prevent YOT2D through maintaining ß cell function, resulting in the reduction of microvascular
complications during childhood and young adulthood.
