Introduction: Circulating microRNAs (miRs) function as mediators of biological responses to the environment and may provide insights into mechanisms for type 2 diabetes (T2D). A limitation of prior studies is their cross-sectional design. We sought to characterize variability in fasting blood glucose (FBG) at 5 time-points over a 12-month period in order to determine whether FBG variability was associated with circulating miR expression and identify miR-associated biological pathways.
Methods: Participants were from a previously completed trial on restorative yoga for overweight/obese adults with prediabetes. FBG variability was defined using the standard deviation across 5 time-points. A subset of participants with high (n=10) vs. low (n=10) FBG variability, matched by age and sex, were evaluated. Expression of 336 miRs collected at baseline was measured with the Fireplex Circulating MicroRNA assay. False discovery rate (FDR) threshold of 0.2 was applied. The miRPathDB database was used to identify KEGG pathways.
Results: A total of 6 miRs (i.e., miR-192, miR-197, miR-206, miR-424, miR-486, miR-93) were differentially expressed between individuals with highly compared to low FBG variability. For the six miRs identified in both batches, 321 KEGG pathways were targeted. The Insulin signaling pathway was targeted by miR-197, miR-206, miR-424, and miR-486; the Insulin secretion pathway was targeted by miR-486; and the type 2 diabetes mellitus pathway was targeted by miR-197, miR-206, miR-424, and miR-486.
Conclusions: Circulating miRs are associated with variability in FBG and miRs target pathways that are known to underlie risk for T2D. The immediate next step is to perform longitudinal analysis of the relationships between FBG and circulating miRs to explore novel pathway targets to derive new insights about mechanisms for T2D.
E. Flowers: None. I.D. Allen: None. A.M. Kanaya: None. B. Aouizerat: None.
National Institute of Diabetes and Digestive and Kidney Diseases (1R21DK117346-01A1)