Pathway to Prevention Study
Natural History Study of the Development of Type 1 Diabetes
The accrual of data from the laboratory and from epidemiologic and prevention trials has
improved the understanding of the etiology and pathogenesis of type 1 diabetes mellitus
(T1DM). Genetic and immunologic factors play a key role in the development of T1DM, and
characterization of the early metabolic abnormalities in T1DM is steadily increasing.
However, information regarding the natural history of T1DM remains incomplete. The TrialNet
Natural History Study of the Development of T1DM (Pathway to Prevention Study) has been
designed to clarify this picture, and in so doing, will contribute to the development and
implementation of studies aimed at prevention of and early treatment in T1DM.
TrialNet is an international network dedicated to the study, prevention, and early treatment
of type 1 diabetes. TrialNet sites are located throughout the United States, Canada,
Finland, United Kingdom, Italy, Germany, Sweden, Australia, and New Zealand. TrialNet is
dedicated to testing new approaches to the prevention of and early intervention for type 1
The goal of the TrialNet Natural History Study of the Development of Type 1 Diabetes is to
enhance our understanding of the demographic, immunologic, and metabolic characteristics of
individuals at risk for developing type 1 diabetes.
The Natural History Study will screen relatives of people with type 1 diabetes to identify
those at risk for developing the disease. Relatives of people with type 1 diabetes have
about a 5% percent chance of being positive for the antibodies associated with diabetes.
TrialNet will identify adults and children at risk for developing diabetes by testing for
the presence of these antibodies in the blood. A positive antibody test is an early
indication that damage to insulin-secreting cells may have begun. If this test is positive,
additional testing will be offered to determine the likelihood that a person may develop
diabetes. Individuals with antibodies will be offered the opportunity for further testing to
determine their risk of developing diabetes over the next 5 years and to receive close
monitoring for the development of diabetes.
The Pathway to Prevention Study is conducted in two parts:
- Monitoring (annual and semi-annual depending on risk)
In Screening , a simple blood test is done to screen for the presence of diabetes-related
biochemical autoantibodies (GAD, IA-2A, mIAA). Islet cell autoantibodies (ICA) and ZnT8A are
also measured in individuals positive for one or more biochemical autoantibodies.
Participants can go to a TrialNet Clinical Center, Affiliate, or request a screening kit to
have their blood drawn by a local physician or laboratory. Participants will be provided
with their screening results within 4-6 weeks.
If autoantibodies are present initially and are confirmed by repeat testing, participants
will be invited to have additional testing in baseline monitoring visit to determine their
average risk of developing diabetes over the next 5 years. The baseline monitoring visit
will include an Oral Glucose Tolerance Test (OGTT), re-testing for biochemical and islet
cell autoantibodies if needed, measurement of HbA1c, and HLA (genetic) typing.
Individuals with less than 3% average risk will be asked to come for follow-up on annual
basis; individuals with greater than average 32% risk will be asked to come for follow-up
visits on semi-annual basis.
Participants will be monitored for possible progression towards type 1 diabetes and may be
offered the opportunity to enter into a prevention study such (e.g., Oral Insulin prevention
study) or an early treatment study if they are diagnosed with type 1 diabetes while
participating in the Natural History Study.
- Individuals 1 to 45 years old who have an immediate family member with type 1
diabetes (such as a child, parent, or sibling)
- Individuals 1-20 years old who have an extended family member with type 1 diabetes
(such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling)
To be eligible a person must not:
- Have diabetes already
- Have a previous history of being treated with insulin or oral diabetes medications.
- Currently be using systemic immunosuppressive agents (topical and inhaled agents are
- Have any known serious diseases