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

Metabolism. 2015 Sep;64(9):1051-9. doi: 10.1016/j.metabol.2015.05.013. Epub 2015 May 28.

Abstract

Introduction: The 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 methods: In 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.

Results: At 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).

Discussion: This 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.

Keywords: Biomarkers; Insulin resistance; MicroRNA; Precision health; Thiazolidinediones.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Blood Glucose / metabolism
  • Databases, Genetic
  • Diabetes Mellitus, Type 2 / prevention & control
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin Resistance / genetics*
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Thiazolidinediones / therapeutic use*

Substances

  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • MIRN320 microRNA, human
  • MIRN486 microRNA, human
  • MicroRNAs
  • Thiazolidinediones
  • 2,4-thiazolidinedione