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, S A Mohammed, Nicola Riccardo Pugliese, Alessia Mongelli, Era Gorica, Samuele Ambrosini, Peter Riederer, Peter Fischer, Margareta Hinterberger, Yustina M. 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
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.