DISCOVERY of Risk Factors for Type 2 Diabetes in Youth

Inclusion Criteria:

Screening will occur to enrich the yield of individuals who are highly predisposed to develop youth-onset type 2 diabetes and include those with all of the criteria in Category A:

• Overweight or obesity with BMI ≥85th percentile

• Age 9-13 year for girls, 10-14 year for boys (inclusion younger for girls as pubertytends to start a year earlier in girls)

• Tanner Stage 2, 3, or 4

• Elevated HbA1c 5.5-6.4%

Participants who meet all of these categories will further need to meet at least one criterion in Category B:

• Family history of type 2 diabetes in 1st or 2nd degree relative

• Personal exposure to maternal diabetes (i.e., gestational diabetes mellitus (GDM) ormother with type 1 or type 2 diabetes while pregnant with participant)

• HbA1c ≥6.0%

• Severe obesity (BMI ≥99th percentile)

• Personal history of intrauterine growth restriction (IUGR), small for gestationalage (SGA), or low birth weight

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 (transplant, cancer, Down Syndrome, Turner Syndrome, Klinefelter Syndrome,ovarian/testicular failure, etc.)

• Medications affecting glucose dynamics during the screening and enrollment period (oral steroids, inhaled steroids >1,000mcg/day past month, atypical antipsychotics,topiramate)

• Prior treatment with insulin

• Use of glucagon-like peptide-1 (GLP-1) receptor agonist or any weight lossmedications in the 6 weeks prior to enrollment

• Planning treatment with glucagon-like peptide-1 (GLP-1) receptor agonist or anyweight loss medications

• Use of metformin or any glucose lowering medication for a reason other thantreatment of diabetes (e.g., for PCOS) in the 6 weeks prior to enrollment

• 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 thequestionnaires to be utilized