Genetic Risk Score Identifies Hidden Type 1 Diabetes in MODY-Negative Patients

A young person walks into a clinic complaining of fatigue and thirst. Blood tests confirm diabetes. The doctor orders genetic testing to rule out MODY—Maturity-Onset Diabetes of the Young—a rare inherited form that strikes before age 25 and runs in families. The lab sends back a negative result. No mutation found. The diagnosis remains a mystery, and so does the treatment plan.

This scenario plays out for roughly four out of every five people referred for MODY testing. Researchers at the University of Exeter decided to investigate what was actually happening in those cases. They studied more than 1,100 insulin-dependent patients who had been sent for genetic testing and received negative results. What they discovered was striking: about one in five of them—roughly 180 people in their cohort—actually had type 1 diabetes all along, just in an atypical form that the standard MODY panel had missed.

The breakthrough came from applying a genetic risk score that Exeter researchers had developed to assess type 1 diabetes risk. Unlike the MODY test, which looks for mutations in a handful of specific genes, this risk score analyzes all known genetic factors that contribute to type 1 diabetes. It's inexpensive and straightforward to run. When the team applied it to patients whose MODY tests had come back empty, the score identified those with type 1 diabetes that had gone unrecognized.

The distinction matters enormously in practice. MODY and type 1 diabetes require different treatment approaches. A patient misdiagnosed as having one when they actually have the other may receive medication that doesn't address their condition, or miss interventions that could help. Kashyap Patel, an associate professor at Exeter and consultant physician in diabetes and endocrinology who led the study, described the clinical reality: distinguishing between these two forms is genuinely difficult, yet getting it right is essential to getting treatment right. The genetic risk score offers a way to cut through that uncertainty for patients who test negative on the standard panel.

The research, published in Diabetes Care and funded by Diabetes UK and the Medical Research Council, has already moved beyond the laboratory. The NHS is now integrating this approach into its routine genetic testing pathway. Kevin Colclough, the lead clinical scientist for the Exeter MODY testing service at the Royal Devon University Healthcare NHS Foundation Trust, emphasized what this means: when a MODY test comes back negative, the lab can now provide additional diagnostic information rather than simply returning an inconclusive result. Patients and their clinicians get answers instead of uncertainty.

Clinicians working in the field recognize the value immediately. Alison Evans, a consultant physician in diabetes and endocrinology at Gloucestershire Hospitals, noted that the ability to differentiate between straightforward type 1 diabetes and rarer forms is invaluable for tailoring treatment to each person's actual condition. Over her years in practice, she has seen more and more diagnostic gray areas—situations where existing tests leave both patient and doctor without clear direction. A tool that reduces that ambiguity helps focus care on what actually works.

Anna Morris, assistant director of research at Diabetes UK, framed the broader significance: accurate diagnosis is the foundation of appropriate treatment and support. For some people, the existing tests simply don't provide that clarity. This research demonstrates how genetic approaches can fill that gap, reducing diagnostic uncertainty and helping clinicians make informed decisions about care. What began as a research question—what's actually happening in those negative MODY cases?—has become a practical tool now embedded in the NHS testing system, potentially improving outcomes for thousands of patients whose diabetes had gone unrecognized or been misidentified.