Circulating RNAs as predictive markers for the progression of type 2 diabetes

Abstract

Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes in the USA, thus, the identification of biomarkers that could be used to predict the progression from prediabetes to T2DM would be greatly beneficial. Recently, circulating RNA including microRNAs (miRNAs) present in various body fluids have emerged as potential biomarkers for various health conditions, including T2DM. Whereas studies that examine the changes of miRNA spectra between healthy controls and T2DM individuals have been reported, the goal of this study is to conduct a baseline comparison of prediabetic individuals who either progress to T2DM, or remain prediabetic. Using an advanced small RNA sequencing library construction method that improves the detection of miRNA species, we identified 57 miRNAs that showed significant concentration differences between progressors (progress from prediabetes to T2DM) and non‐progressors. Among them, 26 have been previously reported to be associated with T2DM in either body fluids or tissue samples. Some of the miRNAs identified were also affected by obesity. Furthermore, we identified miRNA panels that are able to discriminate progressors from non‐progressors. These results suggest that upon further validation these miRNAs may be useful to predict the risk of conversion to T2DM from prediabetes.

Extracellular Vesicle Encapsulated MicroRNAs in Patients with Type 2 Diabetes Are Affected by Metformin Treatment

“…We previously used the same method to analyze plasma miRNA differences in a cohort of prediabetic individuals (METSIM study) where some progressed to T2DM and some remained at prediabetic to identify predictive marker for the onset of T2DM [20]. While the cohorts are different some of the perturbed miRNAs in plasma overlap between METSIM (the METSIM samples were at prediabetic baseline prior to T2DM progression) and MetaHIT cohorts.…”

“…To address this, a modified small RNA sequencing library construction method, as well as a comprehensive data analysis pipeline, that allows for significant improvement of miRNA analysis from biological samples were developed [17,18]. This improved approach has been used in several diabetes related studies, including the identification of circulating miRNAs associated with the progression of T2DM from prediabetic individuals [19,20].…”

MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States

“…Pre-DM patients with higher levels of miR-150 and miR-30a-5p or lower levels of miR-375 and miR-15a were at a higher risk of developing T2D [69]. A miRNA panel consisting of miR-7641-3p, miR-136-5p, miR-490-3p, miR-501-5p, miR-127-5p, miR-4532-5p, miR-483-5p, and miR-210-3p distinguished obese nonprogressors from progressors who developed T2D at 5-year follow-up [77]. Thus, using a panel of miRNAs and other clinical parameters including HbA1c to classify the health status of patients may help in the discovery of the disease before onset.…”

Biomarkers for type 2 diabetes

“…Multiple miRNAs are dysregulated in diabetes making them potential biomarkers for the risk of T2D [30]. However, conflicting results have been published on miRNAs as biomarkers in the risk of T2D, largely due to different study designs (cross-sectional vs. prospective), small sample size (often < 100), and miRNAs measured in the circulation [31], [32], [33], [34], [35]. Further validation studies are needed to identify miRNAs consistently predicting the progression from prediabetes to T2D.…”