TrialNet is a network of 19 clinical centers worldwide that conducts research on the study, prevention, and early treatment of type 1 diabetes (T1D). The TrialNet Pathway To Prevention (TN01) is a screening and monitoring study that was established to provide a source of subjects for enrollment into prevention trials. In addition, the prospectively followed cohort is used to gain new insights into the natural history of pre-type 1 diabetes in patients with increased risk for the disease. The primary aim of the study is to identify subjects for TrialNet prevention and investigation trials, but can also be used for assessing the predictive value of existing and novel risk markers of T1D, and for examining the demographic, immunologic, and metabolic characteristics of individuals at risk for developing T1D.

Participants who are unaffected by T1D but who had a family member with TID and hence increased risk for developing the disease are eligible for enrollment. Screened subjects are tested for pancreatic autoantibodies (glutamic acid decarboxylase, insulin, ICA-512) using a blood screening test. Participants with at least one positive tests for any of the antibodies are eligible for confirmatory autoantibody measurements, and metabolic testing including oral glucose tolerance tests (OGTTs). Subjects under age 18 are re-screened annually, and subjects with some risk for disease can be enrolled in prevention trials or followed prospectively.

Data collected on patients recruited through 2020 are available from the Repository.

The primary aim of the study is to identify subjects for TrialNet prevention and investigation trials, but the cohort is also used for assessing the predictive value of existing and novel risk markers or T1D, and examining the demographic, immunologic, and metabolic characteristics of individuals at risk for developing T1D. The primary outcome measure is onset of diabetes, as defined by the American Diabetes Association (ADA) based on glucose testing or the presence of symptoms of an unequivocal hyperglycemia. Secondary outcome measures include metabolic and autoantibody assessments.

Glucose testing, or the presence of symptoms and unequivocal hyperglycemia

Individuals who met the following criteria were eligible for enrollment:

• Ages 1 to 45 who have an immediate family member with type 1 diabetes (such as a child, parent, or sibling)
• Ages 1 to 20 who have an extended family member with type 1 diabetes (such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling)

Individuals who have diabetes, have a previous history of being treated with insulin or oral diabetes medications, or are currently using systemic immunosuppressive agents are excluded from the study.

This study is ongoing. Initial characteristics of the cohort have been published.