miR-10b and miR-223-3p in serum microvesicles signal progression from prediabetes to type 2 diabetes
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Type 2 diabetes frequently remains undiagnosed for years, whereas early detection of affected individuals would facilitate the implementation of timely and cost-effective therapies, hence decreasing morbidity. With the intention of identifying novel diagnostic biomarkers, we characterized the miRNA profile of microvesicles isolated from retroactive serum samples of normoglycemic individuals and two groups of subjects with prediabetes that in the following 4 years either progressed to overt diabetes or remained stable.
We profiled miRNAs in serum microvesicles of a selected group of control and prediabetic individuals participating in the PREDAPS cohort study. Half of the subjects with prediabetes were diagnosed with diabetes during the 4 years of follow-up, while the glycemic status of the other half remained unchanged.
We identified two miRNAs, miR-10b and miR-223-3p, which target components of the insulin signaling pathway and whose ratio discriminates between these two subgroups of prediabetic individuals at a stage at which other features, including glycemia, are less proficient at separating them. In global, the profile of miRNAs in microvesicles of prediabetic subjects primed to progress to overt diabetes was more similar to that of diabetic patients than the profile of prediabetic subjects who did not progress.
We have identified a miRNA signature in serum microvesicles that can be used as a new screening biomarker to identify subjects with prediabetes at high risk of developing diabetes, hence allowing the implementation of earlier, and probably more effective, therapeutic interventions.
KeywordsPrediabetes Progression Diagnosis Microvesicle Biomarker MicroRNA
We are indebted to the IDIBAPS Biobank, integrated in the Spanish National Biobank Network, for the sample and data procurement. We are grateful to Yaiza Esteban and Lucía-Isabel Alvarado for technical support. We acknowledge the PREDAPS Study investigators: Gabriel Cuatrecasas (EAP Sarria SL), Eduard Tarragó (EAP Bellvitge), M. Isabel Bobé (EAP La Mina), Flora Lopez (EAP Martorell), Martí Birules (EAP Poble Nou), Rosamar DeMiguel (EAP Pubilla Casas), Laura Romera (EAP Raval Nord), Ana Martinez-Sanchez (EAP El Carmel), Belén Benito, Beatriz Bilbeny and Neus Piulachs (EAP Raval Sud).
MP and AN designed the study; XM, XC, SC, LB, CGG, ER, MMC and JFN performed data collection and clinical analysis; CC and MP performed exosome isolation and RNA analysis; SC, MP and CC performed statistical analyses; MP wrote the first draft of the manuscript; all authors provided critical revisions of the manuscript.
This work was supported by grants EFSD/Lilly and an unrestricted grant from Novartis awarded to AN. It also received support from CIBERDEM.
Compliance with ethical standards
Conflict of interest
No potential conflicts of interest relevant to this article were disclosed.
The study was approved by the Ethical Committees of Parc de Salut Mar Clinical of Barcelona (Register 2011/4274/I) and the Hospital Clinic, University of Barcelona (Register 2011/6945).
Written informed consent was obtained from all the participants included in this study, in accordance with the principles of the Declaration of Helsinki.
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