title: Circulating microRNA-320a and microRNA-486 predict thiazolidinedione response: Moving towards precision health for diabetes prevention.
abstract: BACKGROUND
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiological Nursing, University of California, San Francisco, USA. Electronic address: elena.flowers@ucsf.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Flowers
authors.affiliation: Department of Physiological Nursing, University of California, San Francisco, USA; Institute for Human Genetics, University of California, San Francisco, USA.
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, USA.
authors.forename: Fahim
authors.initials: F
authors.lastname: Abbasi
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lamendola
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, USA.
authors.forename: Kaylene M
authors.initials: KM
authors.lastname: Grove
authors.affiliation: Instutue for Health and Aging, University of California, San Francisco, USA.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Fukuoka
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, USA.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Reaven
mesh_terms: D000328:Adult; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D030541:Databases, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C572916:MIRN320 microRNA, human; C560945:MIRN486 microRNA, human; D035683:MicroRNAs; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione
keywords: Biomarkers; Insulin resistance; MicroRNA; Precision health; Thiazolidinediones