Circulating Cell-Free lncRNAs and Their Potential as Epigenetic Biomarkers for Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2DM) is one of the fastest-growing metabolic diseases worldwide, primarily affecting adults, with most diagnoses occurring in individuals over 45. As a polygenic disorder, it is influenced by a complex interaction of environmental, genetic, and epigenetic factors. These factors contribute to its pathophysiology, including insulin resistance, primary β-cell failure, or a combination of both, often associated with oxidative stress. Type 2 Diabetes Mellitus frequently remains undiagnosed for years as patients progress through the prediabetes stage, characterized by hyperglycemia without noticeable symptoms. Moreover, a definitive cure remains elusive. Given the significant global health threat posed by Type 2 Diabetes Mellitus, there is an urgent need to advance research into noninvasive biomarkers for early diagnosis, prognosis, and the prediction of therapeutic responses. Recently, non-coding RNAs (ncRNAs) have attracted considerable attention. Although these molecules do not encode proteins, they play pivotal roles in various cellular processes, and dysregulation of their expression is increasingly linked to diseases. Aberrant ncRNA profiles have been identified in many diabetic patients, particularly those with complications. Recent evidence indicates that epigenetic dysregulation is a key driver in the onset and progression of Type 2 Diabetes Mellitus. These findings highlight non-coding RNAs as crucial players in developing Type 2 Diabetes Mellitus, with significant potential as biomarkers for predicting and monitoring disease progression. Early identification of diabetes or prediabetes can mitigate the risk of long-term complications, including cardiovascular disease, retinopathy, neuropathy, and nephropathy. This chapter focuses on circulating cell-free long non-coding RNAs, specifically linear and circular RNAs, and their roles in developing Type 2 Diabetes Mellitus. These molecules are particularly intriguing due to their unique structural properties and ability to regulate diverse biological processes. As research into circulating cell-free lncRNAs continues to expand, these molecules hold promise for providing novel insights into the disease’s molecular mechanisms, offering new possibilities for early diagnosis, prognosis, and personalized treatment strategies.