TODAY Genetics Study (TODAY Genetics)

General Description

The rise in childhood obesity has been accompanied by an increased prevalence of type 2 diabetes (T2D) mellitus in children and adolescents. Research has shown the importance of adequate treatment and management on the vascular disease progression of T2D in adults, but research on the treatment and clinical course of T2D in youth has been limited. The TODAY (Treatment Options for Type 2 Diabetes in Adolescents & Youth) study was a 3-arm, prospective, randomized, partially blinded clinical trial of treatment for adolescents diagnosed with T2D.

The TODAY Genetics study was an ancillary study of the TODAY interventional trial conducted under the auspices of the TODAY study group.

Individuals diagnosed with T2D before the age of 18 and had BMI ≥ 85th percentile were recruited from TODAY clinical centers and collaborators. Once enrolled, participants were asked to provide a one-time blood sample collection for analysis of diabetes type and DNA extraction. Information on participant and family medical history was also collected.

Note: Given that the TODAY Genetics study was an extension of the main TODAY study, any requestors interested in TODAY Genetics are strongly encouraged to review the TODAY study (https://repository.niddk.nih.gov/studies/today/).

Objectives

The primary objective of the TODAY Genetics study was to explore relationships between candidate genes and T2D using blood and phenotypic information collected from participants. In addition, the study investigated the role of genetics in obesity, insulin resistance, and cardiac risk in T2D patients.

Outcome Measure

This study analyzed genetic data to explore the role of genetics in pediatric patients with T2D. Phenotype data, including participant and family medical history, and laboratory values, including serum glucose, C-peptide, and pancreatic autoimmunity antibodies, were also assessed in subsequent analyses comparing onset of T2D in youth against adult and youth controls.

Criteria

Inclusion Criteria:

• Diabetes by one of the following criteria:
  • For patients diagnosed prior to January 1, 2010
    - Laboratory determination of fasting glucose ≥ 126 mg/dL, or random glucose ≥ 200 mg/dL, or two-hour OGTT glucose ≥ 200 mg/dL documented and confirmed in medical record.
    - Or laboratory determination of HbA1c ≥ 7%.
  • For patients diagnosed after January 1, 2010
    - Laboratory determination of fasting glucose ≥ 126 mg/dL, or random glucose ≥ 200 mg/dL, or two-hour OGTT glucose ≥ 200 mg/dL documented and confirmed in medical record.
    - Or laboratory determination of HbA1c ≥ 6.5%.
• For asymptomatic patients diagnosed with diabetes with a normal fasting glucose but an elevated two-hour glucose during an OGTT, the HbA1c must be ≥ 6%.
• BMI >= 85th percentile documented at time of diagnosis.
• Age < 18 at time of diagnosis.
• Signed informed consent and assent forms as appropriate.

Exclusion Criteria:

• Genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
• Patient on medication known to affect glucose tolerance, insulin sensitivity or secretion within 60 days of the time of diagnosis. If diagnosis is confirmed after the patient has been off the medication for 60 days, the patient may be included. Exclusionary medications include but are not limited to
  • Inhaled steroids at dose above 1000 mcg daily fluticasone equivalent,
  • Oral glucocorticoids,
  • Antirejection or chemotherapy agents (e.g., tacrolimus, L-asparaginase), and
  • Atypical antipsychotics.
• Blood relative of a TODAY participant or another TODAY Genetics participant.

Outcome

Two pediatric studies, TODAY and SEARCH for Diabetes in Youth (SEARCH), and the adult T2D-GENES study led to the formation of the Progress in Diabetes Genetics in Youth (ProDiGY) Consortium. ProDiGY utilized resources from these studies in conjunction with the TODAY Genetics in the first genome-wide association study of youth-onset type 2 diabetes. The team identified seven known genome-wide significant loci and one novel genome-wide significant loci. That study suggested that there were significant overlaps in the genetic makeup of T2D in youth compared to adults, which warrant further exploration and functional analyses to better understand T2D in the youth.