MODY in Ukraine: genes, clinical phenotypes and treatment

What is it about?

Background: Maturity-onset diabetes of the young (MODY) has not been previously studied in Ukraine. We investiated 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 from insulin 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.

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