Circulating miRNAs as predictive biomarkers of type 2 diabetes mellitus development in coronary heart disease patients from the CORDIOPREV study

Authors: JIMENEZ-LUCENA, ROSA - University Hospital Reina Sofia; RANGEL-ZUNIGA, ORIOL - University Hospital Reina Sofia; ALCALA-DIAZ, JUAN - University Hospital Reina Sofia; LOPEZ-MORENO, JAVIER - University Hospital Reina Sofia; RONCERO-RAMOS, IRENE - University Hospital Reina Sofia; MOLINA-ABRIL, HELENA - University Of Seville; YUBERO-SERRANO, ELENA - University Hospital Reina Sofia; CABALLERO-VILLARASO, JAVIER - University Hospital Reina Sofia; DELGADO-LISTA, JAVIER - University Hospital Reina Sofia; PASTOR-CASTANO, JUSTO - University Of Cordova (UCO), Spain; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PEREZ-MARTINEZ, PABLO - University Hospital Reina Sofia; CAMARGO, ANTONIO - University Hospital Reina Sofia; LOPEZ-MIRANDA, JOSE - University Hospital Reina Sofia

Submitted to: Molecular Therapy - Nucleic Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2018
Publication Date: 5/8/2018
Citation: Jimenez-Lucena, R., Rangel-Zuniga, O.A., Alcala-Diaz, J.F., Lopez-Moreno, J., Roncero-Ramos, I., Molina-Abril, H., Yubero-Serrano, E.M., Caballero-Villaraso, J., Delgado-Lista, J., Pastor-Castano, J., Ordovas, J.M., Perez-Martinez, P., Camargo, A., Lopez-Miranda, J. 2018. Circulating miRNAs as predictive biomarkers of type 2 diabetes mellitus development in coronary heart disease patients from the CORDIOPREV study. Molecular Therapy - Nucleic Acids. 12:146-157. https://doi.org/10.1016/j.omtn.2018.05.002.
DOI: https://doi.org/10.1016/j.omtn.2018.05.002

Interpretive Summary: MicroRNAs (miRNAs) are small molecules found in plants and animals that regulate the amount of expression of genes. Blood circulating miRNAs have been associated with different diseases including type 2 diabetes (T2D). Our aim was to identify whether circulating miRNAs provided a better prediction of T2D development than the classical clinical markers. This study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After up 60 months in the study, 107 of them developed T2D. Blood levels of 24 miRNAs were measured at baseline as well as other classical T2D risk biomarkers. Our analysis identified 9 miRNAs, which, when added to classical markers of T2D improved the ability to predict disease development. Our results showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of T2D. Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of T2D in clinical practice.

Technical Abstract: Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers, and they may be a more sensitive way to predict development of the disease than the currently used tools. Our aim was to identify whether circulating miRNAs, added to clinical and biochemical markers, yielded better potential for predicting type 2 diabetes. The study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at baseline by qRT-PCR, and other strong biomarkers to predict diabetes were determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342) than HbA1c alone (AUC = 0.6950). The miRNA and HbA1c-based model did not improve when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI = 2.61-48.65). Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of type 2 diabetes in clinical practice.