Natural History Study of the Development of Type 1 Diabetes (Protocol TN-01)
The Trialnet natural History Study of the Development of T1D is divided into Screening and Monitoring stages. each stage will require separate informed consent for entry. Screening involves testing relatives of individuals with diabetes for the presence of islet autoantibodies. individuals who have autoantibodies will be enrolled into the Monitoring stage. The study will use a prospective cohort design.
The algorithm below shows the flow of participants in the Screening and Monitoring stages. The Screening stage involves measurement of GaD65a, ia-2a, and miaa, (with a positive result for any of these leading to measurement of iCa and ZnT8a) to determine whether the participant is eligible for the Monitoring stage. as additional diabetes-related autoantibodies are discovered and validated, they may also be included in Screening. Participants will be eligible for Monitoring if they have at least two positive autoantibodies on a Screening sample or at least one positive autoantibody on two separate Screening samples. Participants younger than 18 years old who are negative for all autoantibodies will be offered annual autoantibody rescreening until their 18th birthday. Participants 18 or older with a single positive autoantibody on the first Screening sample but no positive autoantibodies on a confirmatory test will be offered annual rescreening for two years.
it is possible that individuals who do not qualify for the monitoring stage might still be eligible for other Trialnet studies. Therefore, they may be contacted in the future so that they can be informed of these studies and/or for the purpose of collecting samples for mechanistic studies about T1D. in addition, they will be contacted periodically to learn if they have developed T1D.
The baseline monitoring visit for those with a single confirmed antibody will include an oral glucose tolerance test (oGTT), Hba1c level, and testing for autoantibodies. Further follow-up in the monitoring stage will depend on the estimated 5-year risk for diabetes according to results of the baseline monitoring and autoantibody tests during the Screening stage.
annual monitoring by an Hba1c level and autoantibodies will be carried out in participants at lower diabetes risk. Semi-annual monitoring by an oGTT, Hba1c level and autoantibodies will occur in participants at higher diabetes risk. Participants in the annual Monitoring Group will enter the Semi-annual Monitoring Group if they develop [GreaterThanorequalTo] 2 positive autoantibodies, an Hba1c [GreaterThanorequalTo] 6.0%, or an increase in Hba1c level [GreaterThanorequalTo] 0.5% from the last test
in addition to samples for autoantibodies, Hba1c, and glucose and insulin levels, samples will also be obtained at routine or interim visits and residual samples stored for mechanistic studies from consenting participants. These will be used by Trialnet-approved investigators or stored indefinitely at a Trialnet core laboratory and/or a niDDK repository site. Future uses will include assessments which address mechanisms involved with the pathogenesis and treatment of T1D and its complications, as well as other conditions for which individuals with diabetes are at increased risk. Participants may still take part in the natural History Study if they choose not to participate in additional mechanistic studies or storage of residual samples.
individuals who qualify for prevention trials based on their risk assessments will be invited to participate in those trials as they become available. individuals who enter a prevention trial will be followed according to the protocol of that trial. However, pertinent data accrued during the trial (conditional upon treatment status in the trial), such as the development of T1D, may be incorporated into the database for the natural History Study.
1. Be willing to give informed consent for the screening procedure.
2. Be aged 1- 45 years (children less than one year of age will not be screened).
3. Have a blood relative with T1D: primarily first degree relatives (siblings, offspring, and parents), but individuals aged 20 years or less who have second or third degree relatives (nieces, nephews, aunts, uncles, grandparents, cousins, half siblings) with T1D will also be eligible. Definition of
* in the proband requires onset of diabetes before age 40 years and prescription of insulin therapy within one year of diagnosis. (This definition is used to limit the inadvertent inclusion of relatives of probands with type 2 diabetes, but will unavoidably exclude relatives of persons who have T1D, but in whom onset was after age 40 years. Ambiguities regarding eligibility, including whether the proband has T1D, will be resolved by a TrialNet Eligibility and Events Committee.)