Scientists identify blood protein that may predict type 1 diabetes

Scientists have taken an important step in predicting who will develop type 1 diabetes months before symptoms appear.

In a paper published online June 29 in Cell Reports Medicine, researchers at the Department of Energy’s Pacific Northwest National Laboratory and their colleagues found that all people who eventually develop islet-type autoimmunity identified a series of altered proteins that are predictive of a condition known as pancreatic islet autoimmunity, a precursor to pancreatic islet autoimmunity. 1 Diabetes.

Scientists caution that the study marks the beginning, not the end, of the search for ways to predict who will develop the disease. Much more work needs to be done to validate the results and test whether they apply to everyone, not just children who are genetically predisposed to develop the disease. .

Biomarkers that detect unresolved autoimmunity could help doctors monitor a patient’s condition, possibly detect deterioration in health, and prompt prompt treatment even before symptoms appear. prize.

The results are the culmination of nine years of research led by PNNL scientist Thomas Metz, which identified hundreds of proteins in more than 8,000 blood samples from nearly 1,000 children at six laboratories in North America and Europe. was investigated.

TEDDY and clues to islet autoimmunity

Children are participating in a large study known as TEDDY (Environmental Determinants of Diabetes in Young People). TEDDY includes children who are more likely to develop her type 1 diabetes than other children due to their genetic makeup.This study is approaching 20 times^th seeks to understand why some children develop the disease and others do not.

In the latest study, PNNL scientists analyzed plasma samples from about 1,000 children from birth to age six. The researchers identified a set of 83 proteins whose combination of alterations predicted which children would develop islet autoimmunity or type 1 diabetes. .

At present, there is no way to know if or when islet autoimmunity or diabetes develops in people with a genetic predisposition. Doctors know that a patient has islet autoimmunity and develops diabetes if he develops at least two islet autoantibodies, but he doesn’t know what causes autoimmunity or when diabetes develops. not.

“What’s interesting about this study is that it opens the door to detecting autoimmunity sooner than we can at the moment,” Metz said. “This gives us the opportunity to learn more about what causes the immune system to activate the body, which may help clarify and understand the mechanisms by which the immune system is acting on the body. ” development of diabetes better than it is today and provides potential targets for intervention. ”

This discovery is the result of tens of thousands of hours of research by PNNL scientists and colleagues around the world. At PNNL, scientists ran samples through an instrument known as a mass spectrometer, and he spent more than 16,000 hours just checking the levels of hundreds of proteins in each of about 8,000 blood samples. After that, countless hours were spent planning the study, recruiting participants, monitoring health, and analyzing the data.

PNNL data analyst Lisa Brammer has developed a machine that analyzes vast amounts of data on hundreds of proteins from about 1,000 children, including multiple blood samples taken from each child from birth to age 6. I created a learning algorithm.

The scientists conducted their research in two stages. During the discovery phase, the team studied her 2,252 blood samples taken from 184 of her children. There, the team identified 376 of her proteins that were altered in patients who later developed islet autoimmunity or type 1 diabetes. The team then conducted a more detailed validation study looking at her 6,426 blood samples from 990 children.

The 83 blood proteins that the research team identified in validation studies are key to several important processes in the body, including: antigen Presentation, Complement and Blood Coagulation, Inflammatory Signaling and Metabolism. The list of proteins matches well with those the researchers have found to be active in the pancreas of diabetic patients. The research team identified these proteins in a previous study conducted through the Human Islet Research Network.

The PNNL team hopes to continue the study by analyzing additional blood samples already taken from the same children as they grow up. These blood samples were collected through TEDDY until the children were 15 years old.

“At this stage, we are trying to understand how we can predict diabetes. The ultimate goal is to prevent the death of critical insulin-producing cells and completely prevent diabetes.” Lead author Ernest Nakayasu said.

In other studies related to diabetes and inflammation, PNNL scientists explored how our body’s insulin-producing cells become vulnerable to autoimmune attack, i.e. how insulin-producing cells in the pancreas We are studying exactly how they are targeted and killed by the body. Researchers are also looking at how omega-3 fatty acids can protect cells.

Searching for Diabetes Biomarkers: We Need a Village

The study included children whose parents or guardians consented to participate. In the United States, research facilities included the University of Colorado, the University of Florida, and the Pacific Northwest Research Institute in Seattle. Children from hospitals in Germany, Sweden and Finland also participated. The University of South Florida served as the data coordinating center.

In addition to Bramer, Metz, and nakayas, PNNL authors include Athena Schepmoes, Thomas Fillmore, Marina Gritsenko, Yuqian Gao, Paul Piehowski, Bryan Stanfill, Daniel Orton, Ronald Moore, Wei-Jun Qian, Richard D. Smith, Bobbie – Includes Jo Webb. -Robertson. Former PNNL scientists Charles Ansong, Bryan Stanfill, Therese Clauss, and Dave Engel also contributed.

Scientists from the National Institutes of Health, the University of Colorado, the University of Turku in Finland, Technical University of Munich, Lund University, and the Pacific Northwest Diabetes Institute also contributed.

The study was funded by the National Institute of Diabetes, Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute for Child Health and Human Development, the National Institute of Environmental Health Sciences, and the National Research and Development Agency. received. General Medicine, Centers for Disease Control and Prevention, JDRF Foundation. Mass spectrometry analyzes were performed at his EMSL, Institute for Environmental Molecular Sciences, a user facility of the DOE Science Office of Science at PNNL.