Rapid Decline in Beta-Cell Function and Increasing Adiposity is Associated with Conversion to Type 2 Diabetes in at Risk Latino Youth

Youth onset type 2 diabetes (T2D) is becoming increasingly prevalent especially among Latinos, and there is limited information on its pathophysiology and causative factors. Here we describe findings from a longitudinal cohort study in 262 Latino children with overweight/obesity at risk of developing T2D with annual measures of oral and intravenous glucose tolerance (IVGTT), body composition and fat distribution.  Logistic binomial regression was used to identify significant predictors in those who developed T2D compared to matched controls, and mixed-effects growth models to compare rates of change in metabolic versus adiposity measures between groups. Overall conversion rate to T2D at year five was 2% (n=6). Rate of decline in disposition index (DI), measured with an IVGTT, over 5 years was 3X higher in cases (─341.7 units/year) compared to the extended cohort (‒106.7 units/year) and 20X higher compared to controls (‒15.2 units/year). Cases had a significantly higher annual increase in fasting glucose, hemoglobin A1c, waist circumference, and trunk fat and there was an inverse correlation between rate of decline in DI and rate of increase in adiposity measures. T2D development in at risk Latino youth is associated with a substantial and rapid decrease in DI that is directly correlated with increase in fasting glucose, HbA1c, and adiposity.