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

Florian A Wenzl; Alessandro Mengozzi; Shafeeq A Mohammed; Nicola Riccardo Pugliese; Alessia Mongelli; Era Gorica; Samuele Ambrosini; Peter Riederer; Peter Fischer; Margareta Hinterberger; Yustina Puspitasari; Thomas F Lüscher; Giovanni G Camici; Christian M Matter; Gian Paolo Fadini; Agostino Virdis; Stefano Masi; Frank Ruschitzka; Edna Grünblatt; Francesco Paneni; Sarah Costantino

doi:10.2337/dc23-0012

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

Diabetes Care. 2023 Jun 1;46(6):1239-1244. doi: 10.2337/dc23-0012.

Authors

Florian A Wenzl¹, Alessandro Mengozzi^{2

3

4}, Shafeeq A Mohammed², Nicola Riccardo Pugliese³, Alessia Mongelli², Era Gorica², Samuele Ambrosini², Peter Riederer⁵, Peter Fischer⁶, Margareta Hinterberger⁶, Yustina Puspitasari¹, Thomas F Lüscher^{1

7}, Giovanni G Camici^{1

8}, Christian M Matter^{2

9}, Gian Paolo Fadini¹⁰, Agostino Virdis³, Stefano Masi^{3

11}, Frank Ruschitzka^{2

9}, Edna Grünblatt^{12

13

14}, Francesco Paneni^{2

8

9}, Sarah Costantino^{2

9}

Affiliations

¹ Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland.
² Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
³ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁴ Scuola Superiore Sant'Anna, Pisa, Italy.
⁵ Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
⁶ Department of Psychiatry, Medical Research Society Vienna D.C., Danube Hospital Vienna, Vienna, Austria.
⁷ Royal Brompton and Harefield Hospitals and Imperial College, London, U.K.
⁸ Department of Research and Education, University Hospital Zurich, Zurich, Switzerland.
⁹ University Heart Center, Cardiology, University Hospital Zurich, Zurich, Switzerland.
¹⁰ University of Padua, Department of Medicine, Padua, Italy.
¹¹ Institute of Cardiovascular Science, University College London, London, U.K.
¹² Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.
¹³ Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
¹⁴ Neuroscience 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aging
Cohort Studies
Diabetes Mellitus, Type 2*
Humans
RNA, Long Noncoding* / genetics

Substances

RNA, Long Noncoding