Circulating microRNA-21 is an early predictor of ROS-mediated damage in subjects with high risk of developing diabetes and in drug-naïve T2D

• Published in: Cardiovascular diabetology Vol. 18; no. 1; pp. 18 - 12
• Main Authors: La Sala, Lucia, Mrakic-Sposta, Simona, Tagliabue, Elena, Prattichizzo, Francesco, Micheloni, Stefano, Sangalli, Elena, Specchia, Claudia, Uccellatore, Anna Chiara, Lupini, Silvia, Spinetti, Gaia, de Candia, Paola, Ceriello, Antonio
• Format: Journal Article
• Language: English
• Published: England BioMed Central 25.02.2019; BMC
• Subjects: 4-Hydroxynonenal; Aged; Aldehydes - blood; Antioxidant response; Antioxidants; Biomarkers; Blood Glucose - metabolism; Cardiovascular disease; Circulating MicroRNA - blood; Circulating MicroRNA - genetics; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - genetics; Diabetic retinopathy; Early Diagnosis; Female; Gene expression; Glucose; Glucose Intolerance - blood; Glucose Intolerance - complications; Glucose Intolerance - diagnosis; Glucose Intolerance - genetics; Glucose tolerance; Homeostasis; Humans; Identification; IGT; Insulin resistance; Kinases; Kruskal-Wallis test; Lipid Peroxidation; Male; Manganese; Metabolism; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miR-21; miRNA; Original Investigation; Oxidative Stress; Predictive Value of Tests; Reactive oxygen species; Reactive Oxygen Species - blood; Risk Assessment; Risk Factors; ROS homeostasis; SOD2; Statistical analysis; Superoxide dismutase; Superoxide Dismutase - blood; T2D; Up-Regulation; Antioxidant response; ROS homeostasis; IGT; T2D; Diabetes; miR-21; Prediabetes; SOD2
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-019-0824-2

Impaired glucose tolerance (IGT) is a risk factor for the development of diabetes and related complications that ensue. Early identification of at-risk individuals might be beneficial to reduce or delay the progression of diabetes and its related complications. Recently, microRNAs emerged as potential biomarkers of diseases. The aim of the present study was to evaluate microRNA-21 as a potential biomarker for the risk of developing diabetes in adults with IGT and to investigate its downstream effects as the generation of reactive oxygen species (ROS), the induction of manganese-superoxide dismutase-2 (SOD2), and the circulating levels of 4-HNE (4-hydroxynonenal). To evaluate the prognostic and predictive values of plasmatic microRNA-21 in identifying metabolic derangements, we tested a selected cohort (n = 115) of subjects enrolled in the DIAPASON Study, whom were selected on ADA criteria for 2hPG. Statistical analysis was performed using ANOVA or the Kruskal-Wallis test as appropriate. ROC curves were drawn for diagnostic accuracy of the tests; positive and negative predictive values were performed, and Youden's index was used to seek the cut-off optimum truncation point. ROS, SOD2 and 4-HNE were also evaluated. We observed significant upregulation of microRNA-21 in IGT and in T2D subjects, and microRNA-21 was positively correlated with glycaemic parameters. Diagnostic performance of microRNA-21 was high and accurate. We detected significant overproduction of ROS by electron paramagnetic resonance (EPR), significant accumulation of the lipid peroxidation marker 4-HNE, and defective SOD2 antioxidant response in IGT and newly diagnosed, drug-naïve T2D subjects. In addition, ROC curves demonstrated the diagnostic accuracy of markers used. our data demonstrate that microRNA-21 is associated with prediabetic status and exhibits predictive value for early detection of glucose imbalances. These data could provide novel clues for miR-based biomarkers to evaluate diabetes.