Significance: The rising global prevalence of diabetes and its debilitating complications give rise to significant disability and premature mortality. Due to the silent nature of diabetes and its vascular complications, and limitations in current methods for detection, there is a need for novel biomarkers for early detection and prognosis. Recent Advances: Metabolic memory and epigenetic factors are important in the pathogenesis of diabetic complications and interact with genetic variants, metabolic factors, and clinical risk factors. Micro(mi)RNAs interact with epigenetic mechanisms and pleiotropically mediate the effects of hyperglycemia on the vasculature. Utilizing mature profiling techniques and platforms, an increasing number of miRNA signatures and interaction networks have been identified for diabetes and its related cardiorenal complications. As a result, these short, single-stranded molecules are emerging as potential diagnostic and predictive tools in human studies, and may function as disease biomarkers, as well as treatment targets.
Critical issues: However, there is complex interaction between the genome and epigenome. The regulation of miRNAs may differ across species and tissues. Most profiling studies to date lack validation, often requiring large, well-characterized cohorts and reliable normalization strategies. Furthermore, the incremental benefits of miRNAs as biomarkers, beyond prediction provided by traditional risk factors, are critical issues to consider, yet often neglected in published studies.
Future directions: All in all, the future for miRNA-based diagnostics and therapeutics for diabetic complications appears promising. Improved understanding of the complex mechanisms underlying miRNA dysregulation, and more well-designed studies utilizing prospective samples would facilitate the translation to clinical use.
Keywords: biomarkers; diabetes; diabetic complications; epigenetics; gene regulation; microRNA; oxidative stress.