Proteins predict who'll develop type 1 diabetes before symptoms appear
Researchers have analyzed the blood of children genetically predisposed to developing type 1 diabetes and identified a set of proteins that predict the autoimmunity that leads to the disease months before symptoms appear.
In type 1 diabetes (T1D), the body’s immune system attacks and destroys the pancreas’ insulin-secreting beta cells. It’s an incurable, chronic condition that affects millions of people worldwide, but the triggers and mechanisms underlying the autoimmune response that causes it are poorly understood.
Proteomics is the large-scale study of proteins or, more specifically, the complete set of proteins, called a proteome, that are expressed by an organism. Proteomics is, amongst other things, used to investigate when and where proteins are expressed and interact and how they’re involved in metabolic pathways. Analyzing proteins can provide a means of identifying the biomarkers of disease.
Researchers from the Pacific Northwest National Laboratory (PNNL) in Washington, searched for biomarkers that might detect the autoimmune process that leads to T1D.
“What’s exciting about this work is that it opens the door to detecting autoimmunity earlier than we can right now,” said Thomas Metz, corresponding author of the study. “This gives us an opportunity to learn more about what causes the immune system to turn on the body. This could help us tease out and understand the mechanisms at play in the development of diabetes better than we do currently and provide potential targets for intervention.”
The islets of Langerhans in the human pancreas contain three types of hormone-secreting cells, one of which is beta cells. Currently, there’s no way to determine if or when a genetically predisposed person will develop the autoimmunity to islet cells that causes them to be destroyed and leads to T1D. A diagnosis is usually made when a person presents to a hospital or healthcare professional with the symptoms of high blood glucose.
The current study was undertaken in two phases. During the discovery phase, researchers studied 2,252 regularly collected blood samples from 184 children from birth to age six, participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study. The TEDDY study is looking at why some genetically predisposed children go on to develop T1D while others don’t. From the children who later developed islet autoimmunity or T1D, the researchers identified 376 altered proteins.
Next, in the validation phase, the researchers examined 6,426 blood plasma samples from 990 children. Using a machine learning algorithm to assist in processing the large number of samples, they identified a set of 83 proteins whose combination of alterations predicted which children went on to develop either islet autoimmunity or T1D. What’s more, the proteins were detected months before the onset of symptoms of the disease.
The researchers say the study is just the beginning of work that, it’s hoped, will be able to predict who will develop T1D. They plan to continue analyzing blood samples taken from children in the TEDDY study up to the age of 15.
More research is needed to verify the results and see whether the findings apply to everyone, not just children drawn from the TEDDY study with a genetic predisposition to developing diabetes. But having a biomarker that detects autoimmunity has the potential to enable monitoring of a patient for worsening health and lead to more prompt medical care, even before symptoms appear, the researchers say.
“At this stage, we’re trying to understand how we might be able to predict diabetes,” said Ernesto Nakayasu, lead author of the study. “Ultimately, the goal is to prevent critical insulin-producing cells from dying and to prevent diabetes altogether.”
The study was published in the journal Cell Reports Medicine.