Evaluation of miRNA-146a, miRNA-34a, and pro-inflammatory cytokines as a potential early indicators for type 1 diabetes mellitus

Background

Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, β-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients.

Aim

Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction.

Patients & methods

Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA.

Results

Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity.

Conclusion

Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes.