A genetic tool originally developed to estimate a person’s risk of developing type 1 diabetes could transform the diagnosis of diabetes in young people, according to a new study from researchers at the University of Exeter. When added to routine genetic testing for maturity-onset diabetes of the young, or MODY, the tool identified previously unrecognised, atypical type 1 diabetes in 16 per cent of patients whose MODY test had found no disease-causing mutation. The finding suggests that a relatively inexpensive analysis of inherited DNA could provide answers for hundreds of people who currently leave genetic clinics with an uncertain diagnosis.
MODY is an uncommon form of diabetes caused by a change in a single gene. Unlike the more familiar forms of diabetes, it is not primarily associated with insulin resistance, obesity, or the autoimmune destruction of insulin-producing pancreatic beta cells. The condition is usually inherited in an autosomal dominant pattern, meaning that a child of an affected parent may have a one-in-two chance of inheriting the relevant genetic variant. MODY often appears before the age of 25, although it can be diagnosed later, and its symptoms may resemble those of type 1 or type 2 diabetes. Correctly identifying it matters because treatment can vary substantially between MODY subtypes and may not require lifelong insulin injections.
In clinical practice, distinguishing MODY from type 1 diabetes can be difficult, particularly when a patient is young and has already begun insulin treatment. Doctors may consider the patient’s age at diagnosis, family history, body weight, blood glucose pattern, insulin production, and the presence or absence of pancreatic autoantibodies. However, none of these clues is definitive in every case. For this reason, patients suspected of having MODY may undergo a blood test that examines a panel of genes known to cause the disorder. The test can confirm a monogenic form of diabetes when a relevant variant is found, but approximately 80 per cent of people referred for testing receive a negative result.
A negative MODY test does not necessarily mean that the patient’s diabetes has been fully explained. It may indicate that the person has type 1 diabetes, another form of diabetes, or a rare genetic cause that is not included in the testing panel. This uncertainty can persist for years, leaving patients and clinicians unsure whether insulin is essential, whether alternative therapies could be effective, or whether relatives should be offered genetic counselling. The Exeter team investigated whether a type 1 diabetes genetic risk score could help close that diagnostic gap without requiring a separate, expensive test.
The researchers studied more than 1,100 people who were receiving insulin and had been referred to the Exeter MODY testing service. Alongside their standard genetic analysis for MODY-associated genes, the participants’ DNA was assessed using a type 1 diabetes genetic risk score. Rather than focusing on a single mutation, a polygenic risk score combines the effects of many genetic variants, each of which may contribute a small amount to disease susceptibility. The Exeter score incorporates known genetic factors associated with type 1 diabetes, including variants involved in immune regulation and the development and function of pancreatic beta cells. By combining these signals, it can estimate whether a person’s inherited profile is more consistent with type 1 diabetes.
Among the patients whose MODY panel returned negative, the score identified 16 per cent—around 180 people—as having a genetic profile compatible with atypical type 1 diabetes. These patients had been referred because their diabetes did not fit a straightforward clinical pattern, making the result particularly significant. In such cases, type 1 diabetes may develop more gradually than usual, appear at an unusually young or old age, occur in someone with a strong family history, or lack the classic autoimmune markers doctors often rely on. A genetic risk score cannot replace clinical assessment, but it can supply an additional layer of evidence when conventional features point in different directions.
The approach is technically different from conventional genetic diagnosis. A MODY test searches for rare, high-impact variants in specific genes; finding one can directly establish the molecular cause of diabetes. The type 1 diabetes score instead evaluates the combined influence of many common variants. Each variant is usually insufficient to cause disease on its own, but their cumulative pattern can shift a person’s probability of developing autoimmune diabetes. This distinction means that the score is not a definitive test in the same way as the discovery of a pathogenic MODY mutation. Its value lies in classification: it helps laboratories and clinicians determine whether a negative MODY result is more likely to represent undiagnosed type 1 diabetes rather than an unexplained or monogenic condition.
The study, published in Diabetes Care, indicates that the score can be incorporated into an established NHS genetic testing pathway rather than requiring patients to undergo a separate referral. Because the analysis uses DNA already collected for MODY testing, laboratories may be able to generate the additional result with relatively little extra cost and delay. Researchers say the method will now be adopted as part of NHS testing, a move that illustrates how a research finding can move directly into routine clinical practice. It could also reduce the need for further investigations, including more costly genetic sequencing, for patients whose initial test is negative.
Kashyap Patel, Associate Professor at the University of Exeter and a Consultant Physician in Diabetes and Endocrinology, said the study addresses one of the most difficult problems in diabetes clinics: distinguishing MODY from type 1 diabetes when the clinical picture is ambiguous. Kevin Colclough, lead clinical scientist for the Exeter MODY testing service at the Royal Devon University Healthcare NHS Foundation Trust, described the work as an example of genetic information being integrated into an existing diagnostic service to produce a more informative result. Alison Evans of Gloucestershire Hospitals NHS Foundation Trust said that differentiating conventional type 1 diabetes from less common forms is essential for tailoring treatment, while Diabetes UK emphasised that a clear diagnosis can improve both medical care and patients’ understanding of their condition. The researchers stress that the score will complement, not replace, clinical judgement, and that further research will be needed to assess how its use affects treatment decisions and long-term outcomes across different populations.
Subject of Research: People
Article Title: Clinical utility of a type 1 diabetes genetic risk score measured as part of MODY genetic testing
News Publication Date: 19-Aug-2026
Web References: https://doi.org/10.2337/dc26-1081
References: Diabetes Care, DOI: 10.2337/dc26-1081
Keywords: diabetes, type 1 diabetes, MODY, maturity-onset diabetes of the young, genetic risk score, polygenic risk score, genetic testing, personalized medicine, medical genetics, autoimmune diabetes
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