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

Barutta, F., Corbetta, B., Bellini, S., Guarrera, S., Matullo, G., Scandella, M., Schalkwijk, C., Stehouwer, C. D., Chaturvedi, N., Soedamah‑Muthu, S. S., Durazzo, M. and Gruden, G. (2021) MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS. Journal of Translational Medicine, 19. 475. ISSN 1479-5876 doi: 10.1186/s12967-021-03142-4

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/102311
Identification Number/DOI	10.1186/s12967-021-03142-4
Refereed	Yes
Divisions	Interdisciplinary Research Centres (IDRCs) > Institute for Food, Nutrition and Health (IFNH)
Publisher	BioMed Central
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