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.
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Eligibility Criteria
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…
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
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