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. 2021 Nov 25;19(1):475.
doi: 10.1186/s12967-021-03142-4.

MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS

Federica Barutta  1 , Beatrice Corbetta  2 , Stefania Bellini  2 , Simonetta Guarrera  3   4 , Giuseppe Matullo  2   5 , Michela Scandella  2 , Casper Schalkwijk  6 , Coen D Stehouwer  6 , Nish Chaturvedi  7 , Sabita S Soedamah-Muthu  8   9 , Marilena Durazzo #  2 , Gabriella Gruden #  2
Affiliations

MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS

Federica Barutta et al. J Transl Med. .

Abstract

Background: MicroRNA-146a-5p (miR-146a-5p) is a key regulator of inflammatory processes. Expression of miR-146a-5p is altered in target organs of diabetic complications and deficiency of miR-146a-5p has been implicated in their pathogenesis. We investigated if serum miR-146a-5p levels were independently associated with micro/macrovascular complications of type 1 diabetes (DM1).

Methods: A nested case-control study from the EURODIAB PCS of 447 DM1 patients was performed. Cases (n = 294) had one or more complications of diabetes, whereas controls (n = 153) did not have any complication. Total RNA was isolated from all subjects and miR-146a-5p levels measured by qPCR. Both the endogenous controls U6 snRNA and the spike (Cel-miR-39) were used to normalize the results. Logistic regression analysis was carried out to investigate the association of miR-146a-5p with diabetes complications.

Results: MiR-146a-5p levels were significantly lower in cases [1.15 (0.32-3.34)] compared to controls [1.74 (0.44-6.74) P = 0.039]. Logistic regression analysis showed that levels of miR-146a-5p in the upper quartile were inversely associated with reduced odds ratio (OR) of all complications (OR 0.34 [95% CI 0.14-0.76]) and particularly with cardiovascular diseases (CVD) (OR 0.31 [95% CI 0.11-0.84]) and diabetic retinopathy (OR 0.40 [95% CI 0.16-0.99]), independently of age, sex, diabetes duration, A1c, hypertension, AER, eGFR, NT-proBNP, and TNF-α.

Conclusions: In this large cohort of DM1 patients, we reported an inverse and independent association of miR-146a-5p with diabetes chronic complications and in particular with CVD and retinopathy, suggesting that miR-146a-5p may be a novel candidate biomarker of DM1 complications.

Keywords: Cardiovascular diseases; MicroRNAs; Retinopathy; Type 1 diabetes.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Fig. 1
Fig. 1
Flow chart for the study population. The map shows the European countries that participated to the EURODIAB study (dark grey)
Fig. 2
Fig. 2
miR-146a-5p expression. A Comparison of miR-146a-5p levels in the serum of DM1 patients with (cases; n = 294) and without (controls; n = 153) micro-macrovascular complications (*p < 0.05 cases vs. controls). B Gender-specific miR-146a-5p expression in both cases and controls (p = ns)
See this image and copyright information in PMC

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