Early diagnosis of gestational diabetes mellitus using circulating microRNAs

Liron Yoffe, Avital Polsky, Avital Gilam, Chen Raff, Federico Mecacci, Agostino Ognibene, Fatima Crispi, Eduard Gratacós, Hannah Kanety, Shali Mazaki-Tovi, Noam Shomron, Moshe Hod

Research output: Contribution to journalArticlepeer-review

Abstract

Design: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and its prevalence is constantly rising worldwide. Diagnosis is commonly in the la te second or early third trimester of pregnancy, though the development of GDM starts early; hence, first-trimester diag nosis is feasible. Objective: Our objective was to identify microRNAs that best distinguish GDM samples from those of healthy pregnant women and to evaluate the predictive value of microRNAs for GDM detection in the first trimester. Methods: We investigated the abundance of circulating microRNAs in the plasma of pregnant women in their first trimester. Two populations were included in the study to enable population-specific as well as cross-population inspection of expression profiles. Each microRNA was tested for differential expression in GDM vs control samples, and their efficiency for GDM detection was evaluated using machin e-learning models. Results: Two upregulated microRNAs (miR-223 and miR-23a) were identified in GDM vs the control set, and validated on a new cohort of women. Using both microRNAs in a logistic-regre ssion model, we achieved an AUC value of 0.91. We further demonstrated the overall predictive value of microRNAs using several types of multivariable machine-learning models that included the entire set of expressed microRNAs. All models achieved high accuracy when applied on the dataset (mean AUC = 0.77). The significance of the classification results was established via permutation tests. Conclusions: Our findings suggest that circulating microRNAs are potential b iomarkers for GDM in the first trimester. This warrants further examination and lays the foundation for p roducing a novel early non-invasive diagnostic tool for GDM.

Original languageEnglish
Pages (from-to)565-577
Number of pages13
JournalEuropean Journal of Endocrinology
Volume181
Issue number5
DOIs
StatePublished - 2019

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