Predicting who is at risk of developing type 1 diabetes, as new drugs now available

(Press-News.org) A test using genetics to predict who is at the highest risk of developing type 1 diabetes could one day be applied to largescale health studies, to identify adults who could benefit from new drugs, new research shows.



Known as a genetic risk score, the test uses all genetic information to predict risk of going on to develop type 1 diabetes.



This genetic risk score also feeds into an online clinical calculator, previously developed by the team led by the University of Exeter and now available to clinicians, which helps identify children at high risk of developing type 1 diabetes. Clinicians can input routine clinical information, such as age, family history (including whether a sibling has type 1 diabetes), blood test results, and a child’s genetic risk score, to generate an estimate of their risk.



In type 1 diabetes, the body’s own immune system attacks insulin-producing beta cells in the pancreas, which means people need to inject insulin daily. The causes are under investigation, but it is known that there is a genetic component.



Knowing who is at highest risk of developing type 1 diabetes in future is crucial, as the United States and UK have recently licensed a new drug called teplizumab, that can delay the clinical diagnosis of disease and the need for insulin by up to three years. The drug is not currently available on the NHS and is under review by NICE. Crucially, it only works if given before symptoms develop.



This earliest stage of type 1 diabetes can be detected using a simple blood test measuring autoantibodies. Produced by the immune system, autoantibodies mistakenly attack the body’s cells rather than attacking bacteria or viruses. The genetic risk score can identify who should be put forward for autoantibody testing, to identify whether they could benefit from the new drugs.



In the latest paper, a research letter, published today in The Lancet Diabetes and Endocrinology, the international team applied the genetic risk score to adults in the Exeter 10,000 cohort, run by the NIHR Exeter Clinical Research Facility. They showed that people who scored in the top ten per cent were at eight times higher risk of being in the early stages of type 1 diabetes.



Professor Richard Oram, at the University of Exeter, who developed the genetic risk score and led the new study, said: “Now that new drugs are available that can delay the onset of diabetes, we urgently need to be able identify who is at high risk of developing the condition, particularly as the drug is only approved before symptoms occur. Our research shows us that we could use this score in large population studies such as Our Future Health to identify who is at the highest risk and offer them autoantibody testing, as an efficient way of identifying adults with early-stage type 1 diabetes who may be eligible for treatment.”



Dr Nick Thomas, at the University of Exeter, added: “This new research builds on our new clinical calculator, which is available for free to clinicians around the world. It will help them predict if a person is high risk, for example if they have type 1 diabetes in the family. Together, this research aims to make it cheaper, more effective, and more accessible to identify who is at high risk of developing type 1 diabetes, so they can be monitored and access treatment as early as possible.”  



The research is supported by the National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre and the NIHR Exeter Clinical Research Facility, as well as Diabetes UK, Breakthrough T1D and Randox.



Dr Lucy Chambers Head of Research Impact and Communications at Diabetes UK, said: “Type 1 diabetes is a serious condition that, in the early stages, can develop silently for months or years before symptoms suddenly appear. This symptomless window is a vital opportunity to intervene.



“This new genetic risk calculator could act as an early radar, helping clinicians identify people who should be offered a simple autoantibody blood test that can spot early-stage type 1 diabetes. This could help unleash the benefits of immunotherapies that can hold off the condition and potentially postpone the need for insulin for years. 



"Innovations like this are key to building effective type 1 diabetes screening pathways, giving us the best chance of getting people the support and treatment they need as early as possible.”



Dr Esther Latres, Senior Vice President of Research at Breakthrough T1D, said: “Breakthrough T1D is committed to advancing research that will help us understand what causes type 1 diabetes and the autoimmune progression. Identifying individuals at elevated genetic risk in early stages of the disease, as determined by the presence of autoantibodies, will allow for the monitoring of disease progression, access to approved therapies, the opportunity to participate in clinical trials, and the reduced risk of complications at the time of a clinical diagnosis.”



Anyone interested in research that can help identify the risk of developing type 1 diabetes can sign up to two trials currently open to recruitment: the ELSA study for children, and the T1DRA study for adults.



The research letter is titled ‘Genetic risk targeted Islet-autoantibody screening for presymptomatic type 1 diabetes in adults’, and is published in The Lancet Diabetes and Endocrinology. Research letters published in the Correspondence section include research findings and are externally peer-reviewed. Unlike Articles containing original data, research letters are shorter and the research they contain is usually preliminary, exploratory, or reporting on early findings. 



The clinical calculator tool for clinicians is available here.

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