The primary objectives of DISCOVERY are to: 1. Identify the physiologic drivers and other determinants of progression to youth-onset T2D by charting the course of changes in glycemia, β-cell function, insulin sensitivity, psychosocial, behavioral, and social determinants of health during this critical period of maturation 2. Inform approaches for precise prediction of which youth are at highest risk of developing T2D during this period. 3. Engage local and central stakeholders to play an active role in the study design and conduct, and provide feedback during follow-up.
Longitudinal studies are needed to identify early contributors to insulin resistance and β-cell dysfunction in youth with obesity, and to explore the interrelationships between the transition through puberty and the evolution of dysglycemia, particularly in the context of psychosocial factors, social determinants of health, and physiologic differences attributable to social factors vs. ancestry.
3,600 youth, aged 9-14 years at enrollment, of all sex, racial and ethnic groups from 15 clinical centers in the US will be included. DISCOVERY participants must have all of the criteria in Category A: Overweight or obesity with BMI ≥85th percentile Age 9-13 years for girls, 10-14 years for boys (inclusion younger for girls as puberty tends to start a year earlier in girls) Pubertal Tanner Stage 2 or 3, or Tanner Stage 4 (without initiation of menses for Tanner 4 girls) HbA1c 5.5-6.4% Participants who meet all of these categories will be further evaluated for at least one criterion in Category B: Family history of T2D in 1st or 2nd degree relative Personal exposure to gestational diabetes mellitus (GDM) HbA1c > 6% Severe obesity (BMI >99th percentile) Personal history of intrauterine growth retardation (IUGR), small for gestational age (SGA), or low birth weight
Principal Investigator