Epigenetic modifications: a valid mechanism for realizing vascular complications and metabolic memory in diabetes? | Ukrainian Medical Journal

Epigenetics is a relatively new scientific field that has recently gained widespread attention in medicine. It explains the molecular mechanisms by which environmental factors influence the formation of pathological phenotypes through post-translational regulation of gene activity during an individual’s development. Epigenetic modifications include methylation, acetylation of certain regions of DNA and chromatin, which are responsible for key signaling pathways and can persist across generations of somatic cells and gametes. These persistent changes can lead to the development of diseases, in particular, insulin resistance syndrome and type 2 diabetes, and contribute to the emergence of cardiovascular complications. It was found that epigenetic changes in type 2 diabetes underlie the phenomenon of «metabolic memory», which was revealed in the DCCT-EDIC and UKPDS studies. These studies did not record the protective effect of long-term normalization of glycemia on the progression of macro- and microvascular complications. Further studies have shown that transient hyperglycemia causes modifications of chromatin structure and gene expression due to the methylation of lysine residues in histone H3, leading to persistent negative changes in signaling pathways. As a result, hyperglycemia, hyperlipidemia, and hypertension occur, which, in turn, provoke an increase in the levels of glycation end products, oxidized lipids, and inflammatory cytokines, known as factors of metabolic and vascular disorders in type 2 diabetes. In general, the study of epigenetic modifications will help to better understand the mechanisms underlying the development of various metabolic disorders and contribute to the development of new approaches to their treatment.

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