Epigenetic regulation by polyphenols in diabetes and related complications

Diabetes mellitus (DM) is a chronic metabolic disorder and one of the most challenging health problems worldwide. Left untreated, it may progress causing serious complications. Genetics, epigenetics, and environmental factors are known to play an overlapping role in the pathogenesis of DM. Growing evidence suggests the hypothesis that the environment induces changes in the early phases of growth and development, influencing health and disease in the adulthood through the alteration in genetic expression of an individual, at least in part. DNA methylation, histone modifications and miRNAs are three mechanisms responsible for epigenetic alterations. The daily diet contains a number of secondary metabolites, with polyphenols being highest in abundance, which contribute to overall health and may prevent or delay the onset of many chronic diseases. Polyphenols have the ability to alter metabolic and signaling pathways at various levels, such as gene expression, epigenetic regulation, protein expression and enzyme activity. The potential efficacy of polyphenolic compounds on glucose homeostasis has been evidenced from in vitro, in vivo and clinical studies. The present review is designed to focus on epigenetic regulation exerted by polyphenolic compounds in DM and their complications, as well as to summarize clinical trials involving polyphenols in DM.