Genetic Risk Score Helps Uncover Hidden Type 1 Diabetes in Suspected MODY: Study
UK: A study published in Diabetes Care suggests that adding a type 1 diabetes genetic risk score to routine genetic testing for maturity-onset diabetes of the young (MODY) could identify previously unrecognized type 1 diabetes in about 1 in 5 patients with negative MODY testing. The approach may improve diagnostic accuracy, reduce the need for additional investigations, and provide clearer explanations for patients whose diabetes remains genetically unexplained after a negative MODY test.
The study, led by Jacques Murray Leech of the Institute of Biomedical and Clinical Sciences, University of Exeter, U.K., and colleagues, evaluated whether incorporating a type 1 diabetes genetic risk score (T1DGRS) into genetic testing for suspected MODY could provide additional diagnostic information in routine clinical practice.
Researchers analyzed 1,129 insulin-treated individuals referred for MODY genetic testing. All participants underwent a genetic panel that included 10 variants used to calculate their T1DGRS. The researchers compared the scores with reference populations with and without type 1 diabetes to estimate the proportion of patients with likely type 1 diabetes.
They found that T1DGRS values among people referred for MODY testing fell between those observed in reference groups with and without type 1 diabetes. Based on these findings, the researchers estimated that 20% (95% CI, 14.9–25.2%) of individuals referred for MODY testing may actually have type 1 diabetes.
Following genetic testing, patients with genetically confirmed MODY did not show an increased T1DGRS. In contrast, those whose MODY testing did not identify a genetic cause had higher scores, consistent with an estimated 26% prevalence of type 1 diabetes in this group.
The association was particularly pronounced among younger patients. The estimated prevalence of type 1 diabetes reached 76.2% in children, compared with 16.8% in adults with genetically unresolved MODY.
Key findings included:
- Age-specific T1DGRS thresholds identified 16.1% (95% CI, 13.8–18.5%) of genetically unresolved MODY cases as probable type 1 diabetes.
- As a pregenetic testing tool, T1DGRS had limited overall discriminatory ability, with an AUC of 0.60.
- Performance was substantially better among children younger than 10 years, with an AUC of 0.83.
- In this younger age group, using T1DGRS could potentially avoid more than half of genetic tests without missing MODY cases.
The researchers concluded that incorporating T1DGRS into routine MODY genetic panels is feasible and can extend genetic assessment beyond monogenic diabetes. The score may help uncover type 1 diabetes among patients whose MODY testing is negative, while its usefulness as a pretesting screening tool appears to depend strongly on age.
Overall, the findings suggest that T1DGRS could improve diagnostic pathways for suspected MODY, particularly in children, by helping distinguish type 1 diabetes from monogenic forms and potentially reducing unnecessary genetic testing.
Reference:
Jacques Murray Leech, Aparajita Sriram, Kevin Colclough, Andrew T. Hattersley, Jayne A. L. Houghton, Thomas W. Laver, Kashyap A. Patel; Clinical Utility of a Type 1 Diabetes Genetic Risk Score Measured as Part of MODY Genetic Testing. Diabetes Care 2026; dc261081. https://doi.org/10.2337/dc26-1081
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