A type 1 diabetes (T1D) genetic risk score (T1DGRS) can identify antibody-negative, C-peptide-positive T1D patients who may otherwise remain undiagnosed. The findings for the same were presented at the European Society of Cardiology Conference 2025.

The study analyzed 1,229 insulin-treated European individuals referred for Maturity-Onset Diabetes of the Young (MODY) genetic testing at a single laboratory. Targeted next-generation sequencing for MODY and a 10-SNP T1DGRS were performed. Population centiles were derived using gold-standard T1D controls.

Before MODY testing, 21% of clinically suspected MODY cases had a T1DGRS consistent with type 1 diabetes. Individuals below the 20th T1DGRS centile were more likely to have monogenic diabetes than those above the 80th centile (24% vs. 6%). Limiting MODY testing to those with T1DGRS below the 80th centile reduced testing by 4.2%, missing 1.3% of monogenic diagnoses.

After genetic testing, T1DGRS identified 102 of 901 unsolved cases (11.3%) as likely atypical T1D. These individuals were younger, had lower body mass index, lower C-peptide levels, and less parental history of diabetes, supporting type 1 diabetes diagnoses.

The results indicate that integrating T1DGRS into MODY workflows can optimize testing and detect atypical type 1 diabetes efficiently.