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来自CORDIOPREV研究的冠心病患者循环miRNA作为2型糖尿病发生的预测生物标志物

Circulating miRNAs as Predictive Biomarkers of Type 2 Diabetes Mellitus Development in Coronary Heart Disease Patients from the CORDIOPREV Study.

作者信息

Jiménez-Lucena Rosa, Rangel-Zúñiga Oriol Alberto, Alcalá-Díaz Juan Francisco, López-Moreno Javier, Roncero-Ramos Irene, Molina-Abril Helena, Yubero-Serrano Elena Maria, Caballero-Villarraso Javier, Delgado-Lista Javier, Castaño Justo Pastor, Ordovás Jose Maria, Pérez-Martinez Pablo, Camargo Antonio, López-Miranda José

机构信息

Lipids and Atherosclerosis Unit, Reina Sofıa University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Córdoba, Spain; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Reina Sofıa University Hospital, University of Córdoba, Córdoba, Spain.

Department of Applied Mathematics I, University of Seville, Seville, Spain.

出版信息

Mol Ther Nucleic Acids. 2018 Sep 7;12:146-157. doi: 10.1016/j.omtn.2018.05.002. Epub 2018 May 8.

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.

摘要

循环微RNA(miRNA)已被提议作为2型糖尿病的生物标志物,与目前使用的工具相比,它们可能是预测该疾病发展的更敏感方法。我们的目的是确定在临床和生化标志物基础上加入循环miRNA是否能更好地预测2型糖尿病。该研究纳入了CORDIOPREV研究中462名基线时的非糖尿病患者。中位随访60个月后,其中107人患了2型糖尿病。在基线时通过定量逆转录聚合酶链反应(qRT-PCR)测量了24种miRNA的血浆水平,并确定了其他预测糖尿病的强生物标志物。受试者工作特征(ROC)分析确定了9种miRNA,将其加入糖化血红蛋白(HbA1c)后,在2型糖尿病早期诊断中的预测价值(曲线下面积[AUC]=0.8342)高于单独使用HbA1c(AUC=0.6950)。当纳入芬兰糖尿病风险评分(FINDRISC)时,基于miRNA和HbA1c的模型并未改善(AUC=0.8293)。Cox回归分析表明,循环水平低的miR-103、miR-28-3p、miR-29a和miR-9以及高的miR-30a-5p和miR-150的患者患病风险更高(风险比[HR]=11.27;95%置信区间[CI]=2.61-48.65)。我们的结果表明,循环miRNA在临床实践中可能潜在地用作预测2型糖尿病发展的新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4d6/6023857/9b22c6503ee3/gr1.jpg

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