ESPE Abstracts

Introduction: Maturity-Onset Diabetes of the Young (MODY) represents the most frequent form of monogenic diabetes. Genetic testing of Czech patients with clinical suspicion on MODY began 22 years ago. Aim of the study was to describe the prevalence of MODY subtypes among referred probands with diabetes and to define their clinical characteristics and possible differences.

Methods: Clinical criteria for genetic testing of MODY genes include age at diagnosis between 6 months and 40 years and absence of pancreatic antibodies. Supporting criteria, of which at least some must be fulfilled, are: positive family history of diabetes, detectable C-peptide several years after diagnosis and absence of metabolic syndrome. Patient’s samples are referred from both paediatric and adult diabetologists from the whole Czech Republic. Main genetic method used is Sanger sequencing. Since 2018, next generation sequencing of genes linked to monogenic forms of diabetes has complemented the genetic investigation.

Results: The Czech registry of MODY consists of 1,788 families (3,539 persons) of which MODY has been genetically clarified in 1,385 patients from 686 families (38%). Glucokinase diabetes (GCK-MODY) was the prevailing MODY subtype (69%) being diagnosed in 962 subjects from 473 families. Second most prevalent MODY subtype (16%) was HNF1A-MODY detected in 111 families (233 persons). HNF4A-MODY represented the third most prevalent subtype (131 persons, 60 families, 9%). Remaining 6% (42 families, 59 patients) of confirmed MODY represented rare forms of monogenic diabetes caused by pathogenic variants in the genes MT-TL1, HNF1B, INS, INSR, WFS1, ABCC8, KCNJ11, RFX6 and CEL. Considering variations between MODY and non-MODY probands who were pharmacologically treated, statistically significant differences were observed at age at diagnoses (non-MODY vs GCK-MODY, HNF1A-MODY, rare MODY, respectively: P≤0.0078) and HbA1c (non-MODY vs GCK-MODY: P=0.0001).

Conclusion: Three subtypes of MODY strongly dominate in the Czech registry of MODY. Patients with no genetic findings in genes tested were diagnosed later and had more variable levels of HbA1c compared to persons with MODY.