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. 2014 Dec 12;9(12):e115209.
doi: 10.1371/journal.pone.0115209. eCollection 2014.

Decreased serum level of miR-146a as sign of chronic inflammation in type 2 diabetic patients

Lucy Baldeón R  1 , Karin Weigelt  2 , Harm de Wit  2 , Behiye Ozcan  3 , Adri van Oudenaren  2 , Fernando Sempértegui  4 , Eric Sijbrands  3 , Laura Grosse  5 , Wilma Freire  6 , Hemmo A Drexhage  7 , Pieter J M Leenen  2
Affiliations

Decreased serum level of miR-146a as sign of chronic inflammation in type 2 diabetic patients

Lucy Baldeón R et al. PLoS One. .

Abstract

Background: There is increasing evidence that chronic inflammation is an important determinant in insulin resistance and in the pathogenesis of type 2 diabetes (T2D). MicroRNAs constitute a newly discovered system of cell regulation and in particular two microRNAs (miR-146a and miR-155) have been described as regulators and biomarkers of inflammation.

Aim: To determine a putative association between the levels of miR-146a and miR-155 in serum of T2D patients, clinical parameters and serological indicators of inflammation.

Methods: We performed quantitative Real Time PCR (qPCR) of microRNAs from serum (56 Ecuadorian T2D ambulatory patients and 40 non-diabetic controls). In addition, we evaluated T2D-related serum cytokines.chemokines and growth factors using a commercially available multi-analyte cytometric bead array system. We correlated outcomes to clinical parameters, including BMI, HbA1c and lipid state.

Results: The Ecuadorian non-diabetic controls appeared as overweight (BMI>25: patients 85%, controls 82.5%) and as dyslipidemic (hypercholesterolemia: patients 60.7%, controls 67.5%) as the patients. The serum levels of miR-146a were significantly reduced in T2D patients as compared to these non-diabetic, but obese/dyslipidemic control group (mean patients 0.61, mean controls set at 1; p = 0.042), those of miR-155 were normal.The serum levels of both microRNAs correlated to each other (r = 0.478; p<0.001) and to leptin levels. The microRNAs did not correlate to BMI, glycemia and dyslipidemia.From the tested cytokines, chemokines and growth factors, we found IL-8 and HGF significantly raised in T2D patients versus non-diabetic controls (p = 0.011 and 0.023 respectively).

Conclusions: This study shows decreased serum anti-inflammatory miR-146a, increased pro-inflammatory IL-8 and increased HGF (a vascular/insular repair factor) as discriminating markers of failure of glucose control occurring on the background of obesity and dyslipidemia.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Expression level of serum miR-146a in Ecuadorian Non-diabetic controls and T2D patients.
Fig. 1 shows mean and standard deviation of the fold change values of miR-146a (reference microRNA sync-cel-mir-39) in the serum of the T2D patients as compared to Non-diabetic controls. Differences between groups were tested using independent T test. Levels of significance were set at p = 0.05 (two-tailed).
Figure 2
Figure 2. Dendrogram of unsupervised hierarchical cluster analysis of the tested serum levels of microRNAs, cytokines, chemokines and growth factors in T2D patients and Non-diabetic controls.
The dendrogram shows the clustering of miR-146a and miR-155, and of the pro-inflammatory cytokines CCL4, IL-6, IL-1β and NGF and of TNF-α, IL-8, HGF and resistin.
See this image and copyright information in PMC

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