Researchers have discovered a new way to detect type 1 diabetes long before the first symptoms appear. A distinct pattern of tiny molecules in the blood – known as microRNAs – can indicate whether the body is beginning to develop the disease. According to the researchers, this opens new opportunities for timely intervention – and perhaps even prevention.
Scientists have worked for many years to develop methods for diagnosing type 1 diabetes as early as possible – ideally before it has damaged the body’s insulin-producing beta cells. This has traditionally involved testing for genetic predisposition or for the presence of autoantibodies that attack the insulin-producing cells.
Nevertheless, both methods have limitations: autoantibodies can only detect type 1 diabetes once the immune attack has begun, whereas genetic predisposition does not always lead to the disease.
Now, researchers have developed a test that uses a panel of microRNAs to identify individuals at a very early stage of type 1 diabetes – possibly even before any signs appear.
“With this panel of microRNAs, we can better predict the risk of developing type 1 diabetes and follow the trajectory. This opens treatment options that can be tailored to the individual – or perhaps type 1 diabetes can even be delayed or prevented altogether,” explains a researcher behind the study, Flemming Pociot, Clinical Professor and Consultant, Steno Diabetes Center Copenhagen, Denmark.
More precise than genetics and antibodies
The researchers aimed to develop an alternative to existing methods for identifying people at risk of type 1 diabetes. Their goal was to create a dynamic risk score for disease development that could detect type 1 diabetes earlier than current autoantibody tests, which only become positive once the autoimmune attack is already underway.
To do this, researchers at Steno Diabetes Center Copenhagen collaborated with colleagues from Australia, India and Hong Kong and others to develop a panel of microRNAs that could help to predict disease progression in type 1 diabetes.
MicroRNAs are small molecules that help to regulate gene activity in cells – much like a remote control adjusts the volume on a television. They can switch certain processes in the body on or off.
Fifty microRNAs reveal diabetes risk
The researchers identified 50 microRNAs that have key roles in insulin production, immune system activity and programmed cell death in the pancreas. The selection was based on both laboratory experiments and previous international studies, and these microRNAs were consistent markers of type 1 diabetes across several population groups.
These microRNAs are involved in regulating the body’s ability to produce and secrete insulin, influencing cell survival or death and controlling immune responses. All are relevant to developing type 1 diabetes.
Researchers analyse the concentrations of these microRNAs to obtain insight into the underlying cellular processes that lead to disease. Each microRNA was given a score based on how strongly it signalled the risk of diabetes. These scores were then combined with age and blood test results using artificial intelligence to generate an overall risk profile.
By detecting the presence – or absence – of these microRNAs in blood samples, researchers can calculate a personalised risk score for developing type 1 diabetes.
Some of the microRNAs only appear when the immune system has already started to attack insulin-producing cells. Others show up – or go missing – much earlier in the disease process.
Test finds disease before symptoms appear
After identifying the microRNA panel, the researchers tested the risk score on blood samples from people with and without type 1 diabetes in Denmark, Australia, India and Hong Kong.
The risk score clearly distinguished between healthy individuals, people with type 1 diabetes and those who had not yet developed symptoms but did later. The risk score proved accurate for up to 84% of participants in an independent validation group – comparable to or better than current testing methods.
The researchers also applied the risk score to people who were not yet diagnosed with type 1 diabetes but eventually developed it. Once again, the risk score successfully distinguished those who eventually developed the disease from those who did not.
According to Flemming Pociot, the ability to identify people at high risk – before they show symptoms – is especially promising.
“We already have drugs that can delay the development of type 1 diabetes, but they need to be given before the immune system destroys the insulin-producing cells,” he says. “The treatments exist, but the real challenge is finding people early enough so that they benefit from the treatments.”
Tailoring treatment to individual needs
According to Flemming Pociot, the microRNA panel could be used in several promising ways to identify people with type 1 diabetes at different stages – and with different disease profiles. This could help to tailor treatment more to individual needs.
For example, some people with type 1 diabetes respond well to islet cell transplantation, whereas others do not. MicroRNA analysis could help to predict who is more likely to benefit.
The same applies to drug treatments: a risk score based on microRNAs might help to identify who is likely to respond to a specific therapy – and who is not.
Finally, Flemming Pociot also sees potential for using the risk score to identify people who may have a “smouldering” form of type 1 diabetes – in which it is slowly progressing without obvious symptoms.
Next step is clinical use
Steno Diabetes Center Copenhagen is now exploring this potential, focusing on detecting type 1 diabetes as early as possible.
The goal is to offer the microRNA-based test to people who have a close relative with type 1 diabetes. These individuals are already being screened for genetic predisposition and autoantibodies – and microRNAs could add a new dimension to that testing.
“The tests may help us to understand how quickly type 1 diabetes is progressing and whether someone without any current signs might still go on to develop it,” explains Flemming Pociot. “Combining this knowledge with the new drugs that can protect the insulin-producing beta cells opens exciting possibilities – not just for treating people with type 1 diabetes but potentially for stopping the disease in its tracks.”
