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DISCOVERY of Risk Factors for Type 2 Diabetes in Youth

Recruiting
Conditions
Diabetes Mellitus Type 2, Childhood-Onset
Registration Number
NCT06525259
Lead Sponsor
George Washington University
Brief Summary

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.

Detailed 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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
3600
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, 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) 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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Type 2 diabetesThrough study completion, an average of 2.5 years

Development of type 2 diabetes, as defined by a hemoglobin A1c (HbA1c) ≥6.5% at an annual or mid-year visit followed by a confirmatory HbA1c ≥6.5% collected within 2 weeks of the first value.

Secondary Outcome Measures
NameTimeMethod
Glycemia, β-cell function, insulin sensitivity, and free fatty acid fluxThrough study completion, an average of 2.5 years

Intermediary changes in glycemia, β-cell function, insulin sensitivity, and free fatty acid flux along the spectrum of normal glycemia to prediabetes to type 2 diabetes.

Trial Locations

Locations (20)

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Arizona State University

🇺🇸

Phoenix, Arizona, United States

Phoenix Children's

🇺🇸

Phoenix, Arizona, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

Johns Hopkins All Children's Hospital

🇺🇸

St. Petersburg, Florida, United States

Johns Hopkins University School of Medicine

🇺🇸

Baltimore, Maryland, United States

Boston Children's/Joslin Diabetes Center/Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Colorado Navajo Nation

🇺🇸

Shiprock, New Mexico, United States

Albert Einstein College of Medicine

🇺🇸

Bronx, New York, United States

NYU Langone Health- Brooklyn

🇺🇸

Brooklyn, New York, United States

NYU Langone Health- Long Island

🇺🇸

Garden City, New York, United States

NYU Langone Health- Manhattan

🇺🇸

New York, New York, United States

Atrium Health

🇺🇸

Charlotte, North Carolina, United States

Wake Forest University

🇺🇸

Winston Salem, North Carolina, United States

Cincinnati Children's Hospital

🇺🇸

Cincinnati, Ohio, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

The University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Baylor College of Medicine / Texas Children's

🇺🇸

Houston, Texas, United States

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