Exploring the link between environmental chemical exposures and epigenetic modifications in diabetes mellitus: A review.

Diabetes mellitus (DM) is a globally prevalent metabolic disorder characterized by impaired glucose homeostasis and insulin secretion. Beyond traditional risk factors like lifestyle and genetics, environmental pollutants, including particulate matter, heavy metals, and persistent organic pollutants, have become significant contributors to DM. One of the key mechanistic pathways through which these pollutants exert their effects is the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates the expression of cytochrome P450 family 1 (CYP1) enzymes. This cascade contributes to increased oxidative stress and systemic inflammation, hallmarks of metabolic impairment. Importantly, these environmental pollutants are also linked to epigenetic modifications, including aberrant DNA methylation, histone modifications, and microRNA dysregulation, which further disrupt insulin sensitivity and β-cell function. This review explores the possible mechanistic crosstalk between AhR/CYP1 pathway activation and epigenetic alterations in the context of diabetes development. By integrating findings from epidemiology, in vivo, and in vitro studies, we provide a summary of how environmental exposures may influence diabetes risk through epigenetic mechanisms. Understanding these interactions not only advances our knowledge of DM etiology but also highlights novel molecular targets for preventive and therapeutic strategies.