LAUSR

MiRNAs are small non-coding RNAs that may contribute to common diseases via epigenetic regulation of gene expression; little is known regarding their role in type 2 diabetes (T2D). We performed miRNA-sequencing and transcriptomic profiling of peripheral monocytes from the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA; N=1,154). We examined associations between miRNAs and prevalent impaired fasting glucose and T2D and evaluated the T2D-associated miRNAs effect on incident T2D. Of 774 detected miRNAs, six (miR-22-3p, miR-33a-5p, miR-181c-5p, miR-92b-3p, miR-222-3p, and miR-944) were associated with prevalent T2D. For five of the six miRNAs (all but miR-222-3p) our findings suggested a doseresponse relationship with impaired fasting glucose and type 2 diabetes. Two of the six miRNAs were associated with incident T2D (miR-92b-3p: HR 1.64, p=1.30E-03; miR-222-3p: HR 1.97, p=9.10E-03 in the highest versus lowest tertile of expression). Most of the T2D associated miRNAs were also associated with HDL cholesterol concentrations. The genes targeted by these miRNAs belong to key nodes of a cholesterol metabolism transcriptomic network. Higher levels of miRNA expression expected to increase intracellular cholesterol accumulation in monocytes are linked to an increase in T2D risk.