Abstract
Background:
Maturity-onset diabetes of the young (MODY) has not been previously studied in Ukraine. We investigated the genetic etiology in a selected cohort of patients with diabetes diagnosed before 18 years of age, and in their family members.
Methods:
Genetic testing of the most prevalent MODY genes (GCK, HNF1A, HNF4A, HNF1B and INS) was undertaken for 36 families (39 affected individuals) by Sanger or targeted next generation sequencing.
Results:
A genetic diagnosis of MODY was made in 15/39 affected individuals from 12/36 families (33%). HNF1A and HNF4A MODY were the most common subtypes, accounting for 9/15 of MODY cases. Eight patients with HNF1A or HNF4A MODY and inadequate glycemic control were successfully transferred to sulfonylureas. Median HbA1c decreased from 67 mmol/mol (range 58–69) to 47 mmol/mol (range 43–50) (8.3% [7.5–8.5] to 6.4% [6.1–6.7]) 3 months after transfer (p=0.006).
Conclusions:
Genetic testing identified pathogenic HNF1A and HNF4A variants as the most common cause of MODY in Ukraine. Transfer to sulfonylureas substantially improved the glycemic control of these patients.
Acknowledgments
We would like to thank all Ukrainian regional children’s endocrinologists for referring patients: Begytova T, Chernysh T, Chorna N, Chumak S, Grabar S, Horoshaya O, Ivanenko L, Lantyh L, Logvinov D, Lychnikova T, Mahaeva V, Pogadayeva N, Shevchenko I, Zaharevich L.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The study was supported by Ministry of Health, Czech Republic - Conceptual Development of Research Organization, Motol University Hospital, Prague, Czech Republic 00064203/6001. A special thanks to the Danish-Ukraine Club. SE is supported by a Wellcome Trust Senior Investigator award.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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