Circulating microRNA-320a and microRNA-486 predict thiazolidinedione response: Moving towards precision health for diabetes prevention

IntroductionThe aims of this study were to compare microRNA (miR) expression between individuals with and without insulin resistance and to determine whether miRs predict response to thiazolidinedione treatment.Materials and methodsIn a sample of 93 healthy adults, insulin resistance was defined as steady state plasma glucose (SSPG) ≥ 180 mg/dL and insulin sensitive as < 120 mg/dL. Response to thiazolidinedione therapy was defined as ≥ 10% decrease in SSPG. We selected a panel of microRNAs based on prior evidence for a role in insulin or glucose metabolism. Fold change and Wilcoxon rank sum tests were calculated for the 25 miRs measured.ResultsAt baseline, 81% (n = 75) of participants were insulin resistant. Five miRs were differentially expressed between the insulin resistant and sensitive groups: miR-193b (1.45 fold change (FC)), miR-22-3p (1.15 FC), miR-320a (1.36 FC), miR-375 (0.59 FC), and miR-486 (1.21 FC) (all p < 0.05). In the subset who were insulin resistant at baseline and received thiazolidinediones (n = 47), 77% (n = 36) showed improved insulin sensitivity. Six miRs were differentially expressed between responders compared to non-responders: miR-20b-5p (1.20 FC), miR-21-5p, (0.92 FC), miR-214-3p (1.13 FC), miR-22-3p (1.14 FC), miR-320a (0.98 FC), and miR-486-5p (1.25 FC) (all p < 0.05).DiscussionThis study is the first to report miRs associated with response to a pharmacologic intervention for insulin resistance. MiR-320a and miR-486-5p identified responders to thiazolidinedione therapy among the insulin resistant group.