DISCOVERY of Risk Factors for Type 2 Diabetes in Youth

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