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Identifying Biomarkers to Predict Type 1 Diabetes

Analyses of thousands of blood samples from children at high genetic risk of developing type 1 diabetes have identified proteins that can predict early stages of the disease. In type 1 diabetes, the immune system launches a misguided attack, called islet autoimmunity, on the insulin-producing β (beta) cells in the pancreatic islets. Islet autoimmunity marks an early stage of type 1 diabetes that occurs prior to the appearance of other symptoms such as high blood glucose (sugar) levels. In many cases, islet autoimmunity progresses to destruction of β cells, leading to type 1 diabetes symptoms and diagnosis. While islet autoimmunity can be detected via the presence of autoantibodies in the blood, there is currently no way to know if or when islet autoimmunity will develop or if an individual will transition from autoimmunity to type 1 diabetes. Therefore, biological markers (biomarkers) that predict development of islet autoimmunity and/or the onset of type 1 diabetes symptoms are highly needed.

The Environmental Determinants of Diabetes in the Young (TEDDY) study—a long-term study following children at high risk of developing type 1 diabetes— seeks to identify what factors trigger or protect against the disease. TEDDY researchers analyzed samples from hundreds of participants and identified protein biomarkers that predict the various stages of type 1 diabetes. Many of these proteins have functions previously implicated in type 1 diabetes development, such as immune processes, metabolism, digestion, and disposal of damaged cells such as β cells. Eighty-three of these proteins were validated as accurate biomarkers of islet autoimmunity and type 1 diabetes development. Further analysis using innovative machine learning tools identified how subsets of these proteins, when measured together, could predict the development of islet autoimmunity and type 1 diabetes diagnosis up to 6 months in advance. Though the accuracy of this prediction strategy needs to be tested in larger and more diverse groups of people, it could lead to improved methods to detect islet autoimmunity before onset and to determine who is likely to progress to type 1 diabetes. Such information would help doctors monitor changes in people’s health and inform prevention strategies. Additionally, the identified biomarkers highlighted specific biological pathways involved in disease development, providing new clues to what causes type 1 diabetes and how it may be prevented or treated.

Nakayasu ES, Bramer LM, Ansong C,…Metz TO, the TEDDY Study Group. Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity. Cell Rep Med 4: 101093, 2023.
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