MODY in Ukraine: genes, clinical phenotypes and treatment

J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1095-1103. doi: 10.1515/jpem-2017-0075.

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.

Keywords: MODY; Ukraine; monogenic diabetes; sulfonylurea; treatment.

MeSH terms

  • Adolescent
  • Blood Glucose / genetics*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Genetic Testing
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Infant
  • Male
  • Mutation
  • Phenotype
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Outcome
  • Ukraine

Substances

  • Blood Glucose
  • Hepatocyte Nuclear Factor 1-alpha
  • Hypoglycemic Agents
  • Sulfonylurea Compounds