How Early Can Type 1 Diabetes Be Detected?

In a breakthrough that could transform lives, a team of Scripps Research scientists have discovered what could be an early biological marker of type 1 diabetes. Testing was initially carried out on mice, with the team claiming that replicating it in humans could help prevent the disease from developing.  

Affecting roughly 1.25 million American children and adults, type 1 diabetes is an autoimmune disease that attacks pancreatic beta cells and eliminates the body's ability to produce insulin. The critical hormone transports sugar out of the bloodstream and into cells, where it's safely converted into energy.

Scientists link anti-insulin T cells with type 1 diabetes autoimmune response

Type 1 diabetes typically develops before the age of 20, with diagnosis usually made after symptoms have appeared. At this point, the disease has already infiltrated the immune system and cut off the body's insulin supply. With the scope to identify biological markers and test for early signs of type 1 diabetes, the Scripps Research team hope to delay the onset of the disease.

Luc Teyton, lead author of the study and professor of immunology and microbiology at the Scripps Research institute says, "The translational aspect of this study is what's most exciting to me. By using single-cell technologies to study the prediabetic phase of disease, we have been able to mechanistically link specific anti-insulin T cells with the autoimmune response seen in type 1 diabetes. And that has given us the confirmation we needed to move into human studies."

Researchers seek to identify genetic signature

To investigate the presence of a genetic signature, Teyton and the team conducted a series of experiments over five years. The research involved analysing blood samples of non-obese diabetic mice during the early stages of type 1 diabetes, then using advanced computational and structural biology technologies to explore how the cells trigger the development of the autoimmune disease.

The study built on previous research conducted more than 25 years ago, which revealed that type 1 diabetes leaves a genetic signature found in immune-regulating molecules known as human leukocyte antigens (HLAs). These proteins are located on the surface of cells and signal the immune system to attack, which is usually beneficial but can be life-threatening when messages are wrong. In type 1 diabetes, HLA proteins mutate and bind to insulin fragments produced by beta cells, which can trigger an autonomous attack on the immune system.

Pinpointing the "P9 switch"

Teyton and the team sought to pinpoint why T cells in the immune system are attracted to HLAs. To do this they sequenced the DNA of individual T cells to reveal an in-depth view of cell function and genetic makeup. One of the key findings was a structural mechanism called the "P9 switch" that allows anti-insulin T cells to identify mutated HLA proteins. They noted that the P9 switch is only present in humans in the early stages of developing type 1 diabetes, which means that a simple blood test could be used to reveal the presence of the destructive cells and kickstart intervention. Now, the team plan to collect blood samples from 30 at-risk humans and monitor for biomarkers and beta cell destruction.

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