Exploring early DNA methylation alterations in type 1 diabetes: implications of glycemic control.

Autor:	Čugalj Kern B; University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Kovač J; University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Šket R; University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Tesovnik T; University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Jenko Bizjan B; University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Galhardo J; Paediatric Endocrinology and Diabetes Unit, Hospital de Dona Estefânia - Central Lisbon University Hospital Center, Lisbon, Portugal.; Lisbon Academic and Clinical Center, NOVA Medical School, Lisbon, Portugal., Battelino T; University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Bratina N; University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Dovč K; University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Jun 05; Vol. 15, pp. 1416433. Date of Electronic Publication: 2024 Jun 05 (Print Publication: 2024).
DOI:	10.3389/fendo.2024.1416433
Abstrakt:	Background: Prolonged hyperglycemia causes diabetes-related micro- and macrovascular complications, which combined represent a significant burden for individuals living with diabetes. The growing scope of evidence indicates that hyperglycemia affects the development of vascular complications through DNA methylation. Methods: A genome-wide differential DNA methylation analysis was performed on pooled peripheral blood DNA samples from individuals with type 1 diabetes (T1D) with direct DNA sequencing. Strict selection criteria were used to ensure two age- and sex-matched groups with no clinical signs of chronic complications according to persistent mean glycated hemoglobin (HbA1c) values over 5 years: HbA1c<7% (N=10) and HbA1c>8% (N=10). Results: Between the two groups, 8385 differentially methylated CpG sites, annotated to 1802 genes, were identified. Genes annotated to hypomethylated CpG sites were enriched in 48 signaling pathways. Further analysis of key CpG sites revealed four specific regions, two of which were hypermethylated and two hypomethylated, associated with long non-coding RNA and processed pseudogenes. Conclusions: Prolonged hyperglycemia in individuals with T1D, who have no clinical manifestation of diabetes-related complications, is associated with multiple differentially methylated CpG sites in crucial genes and pathways known to be linked to chronic complications in T1D. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Čugalj Kern, Kovač, Šket, Tesovnik, Jenko Bizjan, Galhardo, Battelino, Bratina and Dovč.)
Databáze:	MEDLINE
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