Epigenetic crossroads in metabolic and cardiovascular health: the role of DNA methylation in type 2 diabetes and cardiovascular diseases

Type 2 diabetes (T2D) and cardiovascular diseases (CVD), part of the metabolic syndrome (MetS), are major contributors to the global health crisis today. A recent report from the World Health Organisation estimates that 17.9 million lives are lost each year to CVD, and one-third of these are premature. The international diabetes federation estimates that around 537 million adults aged between 20 and 79 years are living with diabetes. People with diabetes are suggested to have twice the risk of developing CVD. Epigenetic modifications are being increasingly recognised as the key mediators linking genetic and environmental conditions to metabolic dysfunction. Among these, DNA methylation plays a crucial role in modulating gene expression and influencing pathways involved in glucose homeostasis, inflammation, and vascular integrity. Despite the advances in our understanding of the role of epigenetic alterations in metabolic diseases, including that of T2D, the mechanisms driving selective methylation changes and their long-term impact on cardiovascular health are still not well understood. This review synthesises the current knowledge on DNA methylation dynamics in T2D and their role towards the progression of CVD and explores their potential as biomarkers and therapeutic targets. Understanding the interplay between metabolism and epigenetics in the pathogenesis of T2D and CVD could provide critical insights for early disease identification and the development of novel epigenome-targeted therapeutic strategies.