Abstract
The prevalence of type 2 diabetes mellitus (T2DM) is increasing dramatically worldwide. Dysregulation of microRNA (miRNA) as key regulators of gene expression, has been reported in numerous diseases including diabetes. The aim of this study was to investigate the expression levels of miRNA-122, miRNA-126-3p and miRNA-146a in diabetic and pre-diabetic patients and in healthy individuals, and to determine whether the changes in the level of these miRNAs are reliable biomarkers in diagnosis, prognosis, and pathogenesis of T2DM. Additionally, we examined the relationship between miRNA levels and plasma concentrations of inflammatory factors including tumor necrosis factor alpha (TNF-α) and interleukin 6 (Il-6) as well as insulin resistance. In this case-control study, participants (n = 90) were allocated to three groups (n = 30/group): T2DM, pre-diabetes and healthy individuals as control (males and females, age: 25–65, body mass index: 25–35). Expression of miRNA was determined by real-time polymerase chain reaction (RT-PCR). Furthermore, plasma concentrations of TNF-α, IL-6 and fasting insulin were measured by enzyme-linked immunosorbent assay. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as an indicator of insulin resistance. MiRNA-122 levels were higher while miRNA-126-3p and miRNA-146a levels were lower in T2DM and pre-diabetic patients compared to control (p<0.05). Furthermore, a positive correlation was found between miRNA-122 expression and TNF-α (r = 0.82), IL-6 (r = 0.83) and insulin resistance (r = 0.8). Conversely, negative correlations were observed between miRNA-126-3p and miRNA-146a levels and TNF-α (r = -0.7 and r = -0.82 respectively), IL-6 (r = -0.65 and r = -0.78 respectively) as well as insulin resistance (r = -0.67 and r = -0.78 respectively) (all p<0.05). Findings of this study suggest the miRNAs can potentially contribute to the pathogenesis of T2DM. Further studies are required to examine the reproducibility of these findings.
Highlights
Diabetes mellitus, as a chronic metabolic disease, is characterized by hyperglycemia due to inadequate insulin production by pancreatic beta cells (T1DM) or insulin resistance(T2DM) [1, 2]
MiRNA-122, miRNA-126, miRNA-146a are associated with inflammation in pre-diabetes and type 2 diabetes mellitus acid (EDTA) for RNA extraction, 2 ml in a CBC tube containing Ethylene diamine tetra acetic acid (EDTA) to measure hemoglobin A1c (HbA1c) and 4 ml in a test tube containing a clot activator for serum separation. dx.doi.org/10.17504/ protocols.io.bax5ifq6 [PROTOCOL DOI]
Increasing levels of inflammatory cytokines specially Tumor necrosis factor alpha (TNF-α) are at the heart of inflammatory cascades linked to insulin resistance [33], as we observed in present study in which levels of TNF-α and IL-6 were significantly higher in diabetic and pre-diabetic patients compared to healthy controls
Summary
As a chronic metabolic disease, is characterized by hyperglycemia due to inadequate insulin production by pancreatic beta cells (T1DM) or insulin resistance (inability to respond properly to insulin)(T2DM) [1, 2]. Fasting blood glucose (FBG), hemoglobin A1c (HbA1c), oral glucose tolerance test (OGTT) and homeostatic model assessment for insulin resistance (HOMA-IR) are among the most common tests that have been used for screening and diagnosis of diabetes mellitus. These parameters can predict the development of T2DM only when disease manifestation in patients have already caused metabolic alterations. In this regard, biomarkers for early detection of T2DM and identification of individuals at risk of developing diabetic complications could potentially complement the use of these parameters [4, 5]. Identifying biological predictors involved in T2DM can disclose new biological pathways involved in this disease as well as early detection, and prognosis of this disease [6]
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