Circulating Long Noncoding RNA Signatures Associate With Incident Diabetes in Older Adults: A Prospective Analysis From the VITA Cohort Study

Author:

Wenzl Florian A.1,Mengozzi Alessandro234ORCID,Mohammed Shafeeq A.2,Pugliese Nicola Riccardo3,Mongelli Alessia2,Gorica Era2,Ambrosini Samuele2,Riederer Peter5,Fischer Peter6,Hinterberger Margareta6,Puspitasari Yustina1,Lüscher Thomas F.17,Camici Giovanni G.18,Matter Christian M.29,Fadini Gian Paolo10,Virdis Agostino3,Masi Stefano311,Ruschitzka Frank29,Grünblatt Edna121314,Paneni Francesco289,Costantino Sarah29

Affiliation:

1. 1Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland

2. 2Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

3. 3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

4. 4Scuola Superiore Sant’Anna, Pisa, Italy

5. 5Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany

6. 6Department of Psychiatry, Medical Research Society Vienna D.C., Danube Hospital Vienna, Vienna, Austria

7. 7Royal Brompton and Harefield Hospitals and Imperial College, London, U.K.

8. 8Department of Research and Education, University Hospital Zurich, Zurich, Switzerland

9. 9University Heart Center, Cardiology, University Hospital Zurich, Zurich, Switzerland

10. 10University of Padua, Department of Medicine, Padua, Italy

11. 11Institute of Cardiovascular Science, University College London, London, U.K.

12. 12Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland

13. 13Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

14. 14Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland

Abstract

OBJECTIVE Long noncoding RNAs (lncRNAs) are involved in diabetogenesis in experimental models, yet their role in humans is unclear. We investigated whether circulating lncRNAs associate with incident type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS A preselected panel of lncRNAs was measured in serum of individuals without diabetes (n = 296) from the Vienna Transdanube Aging study, a prospective community-based cohort study. Participants were followed up over 7.5 years. A second cohort of individuals with and without type 2 diabetes (n = 90) was used to validate our findings. RESULTS Four lncRNAs (ANRIL, MIAT, RNCR3, and PLUTO) were associated with incident type 2 diabetes and linked to hemoglobin A1c trajectories throughout the 7.5-year follow-up. Similar results (for MIAT and PLUTO also in combined analysis) were obtained in the validation cohort. CONCLUSIONS We found a set of circulating lncRNAs that independently portends incident type 2 diabetes in older adults years before disease onset.

Funder

Ludwig Boltzmann Institute of Aging Research Vienna, Austria

Italian Society of Arterial Hypertension

Swiss Heart Foundation

Swiss National Science Foundation

Stiftung für wissenschaftliche Forschung

H.H. Sheikh Khalifa bin Hamad Al Thani Foundation

Holcim Foundation

Kurt und Senta-Hermann Stiftung

EMDO Stiftung

Swiss Life Foundation

Gebauer Stiftung

Olga Mayenfisch Foundation

Lindenhof Foundation

Publisher

American Diabetes Association

Subject

Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine

Reference20 articles.

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