Identification of Stress-related MicroRNA Biomarkers in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Background: Many studies have investigated microRNAs (miRNAs) in the detection of type 2 diabetes mellitus (T2DM). Herein, the dysregulated direction of stress-related miRNAs used as biomarkers of T2DM are summarized and analyzed.

Methods: PubMed, EMBASE, ISI Web of Science, and three Chinese databases were searched for case-control miRNA profiling studies about T2DM. A meta-analysis under a random effect was performed. Subgroup analysis was conducted based on different tissues and species. Sensitivity analysis was conducted to confirm the robustness among studies. The effect size was pooled using ln odds ratios (ORs), 95% confidence intervals (95% CIs), and P-values.

Results: The present meta-analysis included 39 case-control studies with a total of 494 miRNAs. Only 33 miRNAs were reported in three or more studies and, of these, 18 were inconsistent in their direction of dysregulation. Two significantly dysregulated miRNAs (let-7 g and miR-155) were identified in the meta-analysis. Four miRNAs (miR-142-3p, miR-155, miR-21, and miR-34c-5p) were dysregulated in patients with T2DM, whereas five miRNAs (miR-146a, miR-199a-3p, miR-200b, miR-29b and miR-30e) were dysregulated in animal models of diabetes. In addition, two dysregulated miRNAs (miR-146a and miR-21) were highly cornea specific and heart specific. In sensitivity analysis, only miR-155 was still significantly dysregulated after removing studies with small sample sizes.

Conclusions: The present meta-analysis revealed that 16 stress-related miRNAs were significantly dysregulated in T2DM. MiR-148b, miR-223, miR-130a, miR-19a, miR-26b and miR-27b were selected as potential circulating biomarkers of T2DM. In addition, miR-146a and miR-21 were identified as potential tissue biomarkers of T2DM.