The landscape of monogenic diabetes in Italy. Comparisons with other European countries

The information on monogenic diabetes in Italy is sparse, so that disease management relies primarily on data from other European countries, mainly the UK, France and Norway. We describe the largest cohort of Italian patients with monogenic diabetes across wide age-range at diagnosis.

In 2017-2025, 521 White unrelated patients with suspected monogenic diabetes underwent NGS and Sanger sequencing. Variants were classified according to gene-specific expert-panel or ClinGen/ACMG guidelines.

Pathogenic/likely-pathogenic variants were found in 127/521 patients (24.4 %). This proportion was inversely related to age at diagnosis, being only 3 % at > 50 years, raising questions about genetic testing in this group. In contrast to what reported in the UK, France and Norway, GCK-diabetes was the most common (54 %) with HNFAs-diabetes, accounting only for 19 % cases. Variants in syndromic diabetes genes explained 22.8 % cases, a proportion similar to that reported in the UK and in France. The MODY probability calculator achieved a much worse discrimination than in the UK where it was developed, highlighting the need of a high-performance algorithm for Italian patients.

Monogenic diabetes in Italy only partially resembles that in other countries. This information is instrumental to develop a country-specific disease management.