DISCOVERY of Risk Factors for Type 2 Diabetes in Youth

The goal of the DISCOVERY study is to provide innovative critical information regarding the unique natural history of glycemic control, insulin sensitivity, and β-cell function, and their mechanistic determinates, in obese adolescents at risk for developing type 2 diabetes.

The DISCOVERY study will extensively phenotype a large cohort of youth at-risk for type 2 diabetes, as they transition through puberty, and characterize the course of dysfunction in pathophysiological indicators that lead to type 2 diabetes. The knowledge gained from this study of the pathophysiology and epidemiology of youth-onset type 2 diabetes with deep biochemical, clinical, and psychosocial phenotyping will critically inform the design and testing of future treatment and prevention approaches.

Inclusion Criteria: Screening will occur to enrich the yield of individuals who are highly predisposed to develop youth-onset T2D and include those with all of the following criteria: * Overweight or obesity with BMI ≥85th percentile * Age 8-13 year for girls, 9-15 year for boys (inclusion younger for girls as puberty tends to start a year earlier in girls) * Tanner Stage 2, 3, or 4 * Elevated HbA1c 5.5-6.4% Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation: * Diabetes based on history, or HbA1c ≥6.5% in the medical record or at screening * Unable/unwilling to provide consent/participate fully * Conditions predisposing to diabetes or altering the trajectory of puberty * Medications affecting glucose dynamics during the screening and enrollment period * Prior treatment with insulin * Use of glucagon-like peptide-1 (GLP-1) receptor agonist or any weight loss medications in the 6 weeks prior to enrollment * Planning treatment with glucagon-like peptide-1 (GLP-1) receptor agonist or any weight loss medications * Use of metformin or any glucose lowering medication for a reason other than treatment of diabetes (e.g., for PCOS) in the 6 weeks prior to enrollment * Planning treatment with metformin or any glucose lowering medication or planning to use such medications for a reason other than treatment of diabetes (e.g., for PCOS) * Known syndromic/monogenic obesity * Blood disorders impacting HbA1c (e.g., anemia, hemoglobin variants) * Major systemic organ disease * History of bariatric surgery or currently planning bariatric surgery * Current pregnancy or currently planning pregnancy * Use of GnRH agonist, estrogen, or testosterone * Individuals who do not speak English or Spanish, given validation of the questionnaires to be utilized