Endocrine Abstracts

JOINT3570

Background: Monogenic diabetes results from a single-gene defect affecting pancreatic beta cells. Accurate diagnosis enables personalized treatment. While precise European prevalence data are lacking, the U. K., a global leader in monogenic diabetes research, reports an estimated prevalence of 24. 8/100, 000 and an observed prevalence of 5. 8/100, 000. This study assessed diagnostic trends and determined the minimum prevalence of monogenic diabetes in the Czech Republic. The clinical indication criteria for genetic investigation were: positive family history of diabetes, diagnosis of diabetes up to 25 years of age, positive C-peptide and negative pancreatic autoantibodies. Since 2011, milder criteria have been used without the necessity of a positive family history of diabetes and the age of diagnosis of diabetes up to 30 years of age.

Material and Methods: Clinical and genetic data were collected from individuals suspected of having monogenic diabetes referred for genetic testing and registered in the National Registry for Monogenic Diabetes between 1999 and 2023. Covariates were analysed using the t-test, and categorical variables with χ2.

Results: By 2023, we registered 1, 879 families (i. e., probands) with suspected monogenic diabetes, and 728 (39 %) received a confirmed diagnoses (1, 473 individuals from the Registry in total). The causative variant was identified in 13 different genes, most commonly in GCK (69 %), HNF1A (15 %), and HNF4A (8 %). The minimum prevalence of monogenic diabetes was 13. 6/100, 000. The number of referred probands increased from 42 per year between 1999-2001 to 142 in 2023. Between 1999 and 2011, stricter clinical criteria resulted in a detection rate of 67% while milder clinical criteria for genetic testing have led to a currently stable detection rate of 30- 40%. The average age of diabetes diagnosis was 15. 5 (± 9. 4) years, with 76 % of probands having a family history of diabetes.

Conclusion: We reported an increasing referral rate and stable detection rate of monogenic diabetes in the Czech Republic. However, considering the U. K. prevalence estimates, about half of the Czech patients with monogenic diabetes remain un- or misdiagnosed. Supported by Czech Ministry of Health (NW24-01-00160)