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

Čugalj Kern, Barbara (author), Kovač, Jernej (author), Šket, Robert (author), Tesovnik, Tine (author), Jenko Bizjan, Barbara (author), Galhardo, Julia (author), Battelino, Tadej (author), Bratina, Nataša (author), Dovč, Klemen (author)

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.

• Language: English
• Keywords: type 1 diabetes, glycemic control, DNA methylation, diabetes-related complications, long-read sequencing
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 10 str.
• Numbering: Vol. 15, art. 1416433
• PID: 20.500.12556/RUL-166831
• UDC: 61
• ISSN on article: 1664-2392
• DOI: 10.3389/fendo.2024.1416433
• COBISS.SI-ID: 198843395
• Publication date in RUL: 27.01.2025

Record is a part of a journal

• Title: Frontiers in endocrinology
• Publisher: Frontiers Media
• ISSN: 1664-2392
• COBISS.SI-ID: 3340154

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• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.