Predictors of Youth-Onset Type 2 Diabetes: UAB Clinical Center

Minority youth are at elevated risk for type 2 diabetes (T2D) relative to non-Hispanic whites (NHW), with African-Americans (AA) and Hispanic-Americans (HA) showing the greatest increase in prevalence since 2000. Our overarching hypothesis is that underlying genetic differences in minority children interact with

environmental factors in an adverse manner to increase risk for T2D. For example, the elevated beta-cell responsiveness and reduced hepatic insulin extraction exhibited by AA may increase risk for obesity and beta- cell dysfunction in the context of a diet high in sugar and processed starches. HA have both a genetic

predisposition to fatty liver, due to a mutation in the carbohydrate-responsive PNPLA3 gene, and a genetic impairment in the ability to expand peripheral adipose tissue. In the context of weight gain and a high- sugar/processed carbohydrate diet, these genetic factors may increase risk for insulin resistance. The global

purpose of RFA-DK-21-002 is to identify factors that predict conversion to T2D, and that disproportionately predispose minority youth to T2D. With our “University of Alabama at Birmingham (UAB) Clinical Center,” we propose to recruit, phenotype, and follow for 5-years 100 at-risk youth aged 8-16 yr without T2D at baseline

comprised primarily of AA children with extreme obesity. Our team excels in assessment of insulin sensitivity and beta-cell function; assessment of body composition and body fat distribution; evaluation of the intrauterine environment; and conducting longitudinal cohort studies with high retention. Published data indicate that the

greatest risk factors for pediatric T2D are extreme obesity (BMI z score > 2.5), impaired glucose tolerance (2-h glucose >140 mg/dL and