Objective
We will determine the agreement of type 1 diabetes associated autoantibody assay results between the five most commonly used commercial and consumer-based clinical reference laboratories in the United States in people who screen positive for early pre-symptomatic (stage 1 or 2) of type 1 diabetes, people who screen negative for stage 1 or 2 type 1 diabetes, children newly diagnosed with type 1 diabetes who have a single or multiple type 1 diabetes associated autoantibodies and in children newly diagnosed with type 2 diabetes.
To those that screen positive for early pre-symptomatic (stage 1 or 2) of type 1 diabetes, we will have regular contact with them and their healthcare providers to determine if they are following our recommendations for follow-up visits and to assess barriers to following recommendations. We will also determine which individuals are diagnosed with type 1 diabetes, which will help us determine the accuracy of each laboratory test over time.
Background Rationale
Screening for pre-symptomatic (stage 1 and 2) type 1 diabetes (T1D) can be done by measuring T1D associated islet autoantibodies (IA). IA testing is readily available clinically, and it is likely that screening through commercial and consumer based clinical laboratories will increase if a therapy to treat individuals with pre-symptomatic T1D becomes available. The results of IA assays seem to vary widely among laboratories. Knowing how results from commonly used laboratories compare in children with different stages and types of diabetes is important so that patients and families can be counseled more appropriately regarding the risk of clinical T1D development. For individuals that screen positive for early type 1 diabetes, follow-up has not been done outside of a clinical research trial. As follow-up appointments move into clinical care with a healthcare provider, it is important to determine if the recommended tests can be done at the recommended frequency and what barriers exist. By following screening-detected people over time, how well islet autoantibody tests from various clinical laboratories identify and predict type 1 diabetes will also be determined.
Description of Project
Screening for pre-symptomatic (stage 1 and 2) type 1 diabetes (T1D) can be done by measuring T1D associated islet autoantibodies (IA). IA testing is readily available clinically, and it is likely that screening through commercial and consumer based clinical laboratories will increase if a therapy to treat individuals with pre-symptomatic T1D becomes available.
The results of IA assays seem to vary widely among laboratories. Knowing how results from commonly used laboratories compare is important so that patients and families can be counseled more appropriately regarding the risk of clinical T1D development.
In this study, we will determine the agreement of T1D associated autoantibody assay results between commonly used commercial and consumer-based clinical laboratories. We currently lead a program AsktheExperts (EXPERTS) (asktheexperts.org), which is a resource for screening detected families and their healthcare providers. When individuals who have screened positive for T1D associated autoantibodies contact us, we provide confirmation testing. We will ask these individuals who screen positive for islet autoantibodies and are in early pre-symptomatic stages (stage 1 or 2) of type 1 diabetes if we can collect additional blood draw and finger poke samples. We will then send these samples to five major laboratories in the United States to determine how well the type 1 positive and negative results agree for each of the four major autoantibodies (GADA, IA-2A, mIAA and ZnT8A) in each sample. We will also collect samples in children who screen negative for type 1 diabetes, children diagnosed with type 1 diabetes who have 1 or multiple type 1 diabetes associated autoantibodies and in children who have no antibodies at diagnosis with type 2 diabetes.
In addition to confirmation testing, we also provide help with follow-up recommendations through our EXPERTS program. In this research study, we will be contacting families and healthcare providers every 3 months to 1 year, depending on their age and stage of type 1 diabetes, to determine if they are following our recommendations and to assess barriers to following recommendations. We will also determine which individuals are diagnosed with type 1 diabetes, which will help us determine the accuracy of each laboratory test over time.
Anticipated Outcome
We anticipate that the concordance between type 1 diabetes associated autoantibody results from different labs will be unacceptably low and support the need for a confirmation tests at an autoantibody core reference laboratory. We also anticipate that the frequency of follow-up visits for screening detected individuals at risk for type 1 diabetes will be less in clinical practice than in the setting of a clinical research study.
Relevance to T1D
Being able to reliably predict who will develop or who has type 1 diabetes is important. Type 1 diabetes associated antibodies are the one marker in the blood that is used to identify type 1 diabetes early and to distinguish type 1 diabetes from other type of diabetes. Because this test is important and can be done at many different laboratories, we need to understand how test results compare and which ones are able to best identify and predict progression to type 1 diabetes.