197-LB: microRNA Expression Profiles and Progression from Normoglycemia to Prediabetes in a Biracial Cohort

Background: MicroRNA (miRNA) profiles are associated with diabetes risk, but data on prediabetes are scant.

Methods: We studied participants (age 49.7 ±5.42 y; BMI 28.6 ±5.77 kg/m2) in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study, whose primary outcome was progression from normoglycemia to prediabetes (IFG/IGT) during 5-y follow up. We analyzed miRNA expression in participants with incident prediabetes (Progressors, n=10) and a matched group of Nonprogressors (n=10). Total RNA was extracted from plasma. NGS sequencing libraries were prepared using QIAseq miRNA Library Prep Kit and RNA sequencing was performed by QIAGEN Genomic Services. Over 12 million reads per samples were performed. To minimize false discovery, Benjamini-Hochberg corrected p-values were used to assess the significance of differential miRNA expression.

Results: Based on entries in mirbase_20, we identified 226 known miRNAs that were expressed at >1tags per million (TPM) and 151 known microRNAs that were expressed at >10 TPM in all samples analyzed. 25 miRNAs were differentially expressed in baseline plasma from Progressors to prediabetes vs. Nonprogressors (P=0.04- <0.0001). The top 5 most upregulated miRNAs in Progressors (vs. Nonprogressors) were miR 216a-5p, miR 217, miR 211-5p, miR 149-5p and miR 204-5p (log fold-change 3.61 to 6.49, P<0.0001). The top 5 most downregulated miRNAs in Progressors (vs. Nonprogressors) were miR 34c-5p, miR 550a-3p, miR 3200-3p, miR 144-5p and miR 144-3p (log fold-change -2.26 to -3.79, P= 0.0009-<0.0001). The most differentially expressed miRNA (miR 216a-5p; 6.49-log-fold higher in Progressors) is linked to the regulation of 78 genes, of which. 30 are involved in glucose, lipid, endocrine and metabolic pathways.

Conclusions: Plasma miRNA expression profile at baseline distinguished progressors to prediabetes from nonprogressors during longitudinal follow-up in the POP-ABC study. miR 216a-5p may be a novel biomarkers of early dysglycemia.