Objective
Our primary objective is to better understand why T1D progresses more quickly in some people than in others. Using state-of-the-art analyses of serum samples from individuals who do or do not progress quickly to T1D, we expect to find features (i.e., “biomarkers”) that can predict disease progression and may identify new targets for improved and/or novel interventional approaches.
Background Rationale
While new technologies such as insulin pumps and continuous glucose monitoring have been helpful in the day-to-day management of T1D, major burdens remain for T1D patients and their families, including reduced lifespan. As a result of many years of screening efforts, we now know that nearly everyone who has more than one T1D autoantibody will eventually develop disease. However, we do not yet know very much about how quickly that will happen: for some people, it will be decades between the time that antibodies are first detected and the time a person is diagnosed with overt T1D and starts insulin treatment; for others, it may only be months. The benefits of better predicting the rate of disease progression through analysis of blood serum, the overarching goal of this highly collaborative research project, are at least three-fold: for one, serum can be sampled relatively easily; it may help individuals to better understand and manage their personal disease trajectories; and from a larger perspective, it may allow scientists and clinicians to better tailor clinical trials that seek to delay, prevent or even revert overt T1D.
Description of Project
Owing to many years of screening efforts, we now know that nearly everyone who has more than one type 1 diabetes (T1D) autoantibody will eventually develop disease. However, we do not yet know very much about how quickly that will happen: for some people, it will be decades between the time that antibodies are first detected and the time a person is diagnosed with overt T1D and starts insulin treatment; for others, it may only be months. To address this problem, we are focusing our research efforts on potential changes in the composition of patient blood serum over the course of disease development. In what is arguably the largest serum study ever conceived for patients at risk for T1D, we are working collaboratively with colleagues across North America who have access to various state-of-the art technology platforms as well as established track records in high-throughput serum analyses. Our study will use ~700 serum samples collected at multiple time points from autoantibody-positive individuals who progressed quickly to T1D and from those who progressed more slowly; all of the samples are provided by the Type 1 Diabetes TrialNet consortium, an international network that screens individuals for T1D autoantibodies. Altogether, we will generate wide-ranging, diversified and detailed data sets comprising many millions of individual datapoints that subsequently will be mined for the identification and validation of “biomarkers” that can help us to better predict T1D risk, development and/or progression; that can be leveraged for improved interventional study design; and that will be made publicly available to establish a comprehensive data resource for reference, orientation and future research efforts.
Anticipated Outcome
Our study will generate uniquely comprehensive and highly diverse data sets that track potential changes in the composition of blood serum across the stages of T1D development. While we will analyze all of these data to identify novel markers for T1D risk, development and progression as well as potential targets for future therapeutic intervention, a key outcome of our work is the public sharing of those data sets with T1D scientists and clinicians worldwide. We believe that such a widely collaborative approach has the most promise to translate the broad array of data points that we will generate into practical applications such as personalized T1D risk assessment, a better understanding of the disease process that leads to slower or faster T1D development, and eventually the design of novel and/or improved strategies for T1D delay, prevention and reversal.
Relevance to T1D
The type of data we will generate and analyses we intend to perform here are highly relevant to T1D as they may permit the establishment of personalized T1D risk assessment and disease management strategies; will promote a better understanding of the underlying disease processes by which T1D develops and progresses; can contribute to the design of improved interventions that will delay, prevent and/or revert T1D; and, following the prompt public sharing of our vast data sets, will enlist the ingenuity, expertise and dedication of T1D scientists and clinicians worldwide to accelerate our pace towards the cure of T1D.