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miR-10b and miR-223-3p in serum microvesicles signal progression from prediabetes to type 2 diabetes

  • M. Parrizas
  • X. Mundet
  • C. Castaño
  • S. Canivell
  • X. Cos
  • L. Brugnara
  • C. Giráldez-García
  • E. Regidor
  • M. Mata-Cases
  • J. Franch-NadalEmail author
  • A. NovialsEmail author
Original Article
  • 37 Downloads

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

Prediabetes Progression Diagnosis Microvesicle Biomarker MicroRNA 

Notes

Acknowledgements

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).

Author contributions

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.

Funding

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.

Ethical approval

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).

Informed consent

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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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  1. 1.Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM)BarcelonaSpain
  2. 2.Pathogenesis and Prevention of Diabetes LaboratoryAugust Pi i Sunyer Biomedical Research Institute (IDIBAPS)BarcelonaSpain
  3. 3.redGDPS FoundationMadridSpain
  4. 4.DAP-Cat Group, Research Support UnitUniversity Institute for Research in Primary Care Jordi Gol (IDIAPJGol)BarcelonaSpain
  5. 5.Autonomous University of BarcelonaBarcelonaSpain
  6. 6.Primary Health Care Center Sant Martí de Provençals, Catalan Health InstituteBarcelonaSpain
  7. 7.Department of Internal MedicineHealth Sciences Research Institute and University Hospital Germans Trias i PujolBarcelonaSpain
  8. 8.Preventive Medicine ServiceUniversity Hospital Infanta ElenaMadridSpain
  9. 9.Preventive Medicine, Public Health and History of Science DepartmentComplutense University of MadridMadridSpain
  10. 10.Epidemiology and Public Health Networking Biomedical Research Centre (CIBERESP)MadridSpain
  11. 11.Health Research Institute, Hospital Clínico San Carlos (IdISSC)MadridSpain
  12. 12.Primary Health Care Center La Mina, Catalan Health InstituteSant Adrià De Besòs, BarcelonaSpain
  13. 13.Department of MedicineUniversity of BarcelonaBarcelonaSpain

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