DISCOVERY of Risk Factors for Type 2 Diabetes in Youth

George Washington University (GW)

Status: Not yet enrolling

Conditions: Diabetes Mellitus Type 2, Childhood-Onset

Study type: Observational

Funder types: Other

Identifiers

NCT06525259

U01DK134971 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 3,600 estimated patients

Sex: All

Ages: 9 to 14 years old

Volunteers: No Healthy Volunteers

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 puberty tends to start a year earlier in girls)
• Tanner Stage 2 or 3 or Tanner Stage 4 (without initiation of menses for Tanner 4 girls)
• 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) or mother 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 gestational age (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 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
• 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