Significance of circulating microRNAs in diabetes mellitus type 2 and platelet reactivity: bioinformatic analysis and review

Cardiovasc Diabetol. 2019 Aug 30;18(1):113. doi: 10.1186/s12933-019-0918-x.


In the light of growing global epidemic of type 2 diabetes mellitus (T2DM), significant efforts are made to discover next-generation biomarkers for early detection of the disease. Multiple mechanisms including inflammatory response, abnormal insulin secretion and glucose metabolism contribute to the development of T2DM. Platelet activation, on the other hand, is known to be one of the underlying mechanisms of atherosclerosis, which is a common T2DM complication that frequently results in ischemic events at later stages of the disease. Available data suggest that platelets contain large amounts of microRNAs (miRNAs) that are found in circulating body fluids, including the blood. Since miRNAs have been illustrated to play an important role in metabolic homeostasis through regulation of multiple genes, they attracted substantial scientific interest as diagnostic and prognostic biomarkers in T2DM. Various miRNAs, as well as their target genes are implicated in the complex pathophysiology of T2DM. This article will first review the different miRNAs studied in the context of T2DM and platelet reactivity, and subsequently present original results from bioinformatic analyses of published reports, identifying a common gene (PRKAR1A) linked to glucose metabolism, blood coagulation and insulin signalling and targeted by miRNAs in T2DM. Moreover, miRNA-target gene interaction networks built upon Gene Ontology information from electronic databases were developed. According to our results, miR-30a-5p, miR-30d-5p and miR-30c-5p are the most widely regulated miRNAs across all specified ontologies, hence they are the most promising biomarkers of T2DM to be investigated in future clinical studies.

Keywords: Bioinformatic analysis; Biomarker; Diabetes mellitus type 2; Diagnosis; MicroRNA; Platelet reactivity; Prognosis; miRNA–gene target interaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Glucose / genetics*
  • Blood Glucose / metabolism
  • Blood Platelets / metabolism*
  • Circulating MicroRNA / blood*
  • Circulating MicroRNA / genetics
  • Computational Biology*
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / blood*
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics
  • Databases, Genetic
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / genetics
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genetic Markers
  • Humans
  • Platelet Activation / genetics*
  • Protein Interaction Maps


  • Blood Glucose
  • Circulating MicroRNA
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • Genetic Markers
  • PRKAR1A protein, human