Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization

Diabetes Care. 2014;37(5):1375-83. doi: 10.2337/dc13-1847. Epub 2014 Jan 29.


Objective: This study sought to identify the profile of circulating microRNAs (miRNAs) in type 2 diabetes (T2D) and its response to changes in insulin sensitivity.

Research design and methods: The circulating miRNA profile was assessed in a pilot study of 12 men: 6 with normal glucose tolerance (NGT) and 6 T2D patients. The association of 10 circulating miRNAs with T2D was cross-sectionally validated in an extended sample of 45 NGT vs. 48 T2D subjects (65 nonobese and 28 obese men) and longitudinally in 35 T2D patients who were recruited in a randomized, double-blinded, and placebo-controlled 3-month trial of metformin treatment. Circulating miRNAs were also measured in seven healthy volunteers before and after a 6-h hyperinsulinemic-euglycemic clamp and insulin plus intralipid/heparin infusion.

Results: Cross-sectional studies disclosed a marked increase of miR-140-5p, miR-142-3p, and miR-222 and decreased miR-423-5p, miR-125b, miR-192, miR-195, miR-130b, miR-532-5p, and miR-126 in T2D patients. Multiple linear regression analyses revealed that miR-140-5p and miR-423-5p contributed independently to explain 49.5% (P < 0.0001) of fasting glucose variance after controlling for confounders. A discriminant function of four miRNAs (miR-140-5p, miR-423-5p, miR-195, and miR-126) was specific for T2D with an accuracy of 89.2% (P < 0.0001). Metformin (but not placebo) led to significant changes in circulating miR-192 (49.5%; P = 0.022), miR-140-5p (-15.8%; P = 0.004), and miR-222 (-47.2%; P = 0.03), in parallel to decreased fasting glucose and HbA1c. Furthermore, while insulin infusion during clamp decreased miR-222 (-62%; P = 0.002), the intralipid/heparin mixture increased circulating miR-222 (163%; P = 0.015) and miR-140-5p (67.5%; P = 0.05).

Conclusions: This study depicts the close association between variations in circulating miRNAs and T2D and their potential relevance in insulin sensitivity.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / metabolism
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics*
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • Insulin / administration & dosage
  • Insulin / pharmacology
  • Insulin Resistance / genetics*
  • Male
  • Metformin / therapeutic use
  • MicroRNAs / metabolism*
  • Middle Aged
  • Pilot Projects
  • Young Adult


  • Biomarkers
  • Hypoglycemic Agents
  • Insulin
  • MicroRNAs
  • Metformin