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Circulating long noncoding RNA signatures associate with incident diabetes in older adults: a prospective analysis from the VITA cohort study

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posted on 2023-04-11, 18:17 authored by 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

  

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 (VITA) 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 employed to validate our findings.

Results: Four lncRNAs (ANRIL, MIAT, RNCR3, and PLUTO) were associated with incident type 2 diabetes and linked to HbA1c trajectories throughout the 7.5-year follow-up. Similar results (for MIAT and PLUTO also in combined analysis) were obtained in the validation cohort.

Conclusion: We found a set of circulating lncRNAs which independently portends incident type 2 diabetes in older adults years before disease onset.

Funding

F.A.W. is supported by the Foundation for Cardiovascular Research and the Lindenhof Foundation. A.M. is the recipient of an International Grant from the Italian Society of Arterial Hypertension. S.A.M. and S.A. are the recipients of a Forschungskredit Candoc grant from the University of Zürich. P.R., P.F., M.H. and E.G. conducted the VITA study under the support of the Ludwig Boltzmann Institute of Aging Research Vienna, Austria. C.M.M. is funded by the Swiss National Science Foundation (310030_146923 and 310030_165990) and the Swiss Heart Foundation. F.P. is the recipient of a H.H. Sheikh Khalifa bin Hamad Al Thani Foundation Assistant Professorship at the Faculty of Medicine, University of Zürich. This work was supported by the Swiss National Science Foundation (n. 310030_197557), the Swiss Heart Foundation (n. FF19045), the Stiftung für wissenschaftliche Forschung, the Olga Mayenfisch Foundation, the Swiss Life Foundation, the Kurt und Senta-Hermann Stiftung, the EMDO Stiftung and the Schweizerische Diabetes-Stiftung (to F.P.); the Holcim Foundation, the Swiss Heart Foundation, the Swiss Life Foundation and the Gebauer Stiftung (to S.C.).

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    Diabetes Care

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    Type 2 DiabetesOlder AdultsBiomarkersNon-coding RNAsCohort

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