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

• Published in: Journal of translational medicine Vol. 19; no. 1; p. 475
• Main Authors: Barutta, Federica, Corbetta, Beatrice, Bellini, Stefania, Guarrera, Simonetta, Matullo, Giuseppe, Scandella, Michela, Schalkwijk, Casper, Stehouwer, Coen D, Chaturvedi, Nish, Soedamah-Muthu, Sabita S, Durazzo, Marilena, Gruden, Gabriella
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.11.2021; BioMed Central; BMC
• Subjects: Biomarkers; Body mass index; Cardiovascular diseases; Case-Control Studies; Complications and side effects; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - genetics; Diabetic angiopathies; Diabetic Retinopathy; Genetic aspects; Health aspects; Humans; Inflammation; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Pathogenesis; Patients; Physiological aspects; Regression analysis; Retinopathy; Risk factors; snRNA; Triglycerides; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Type 1 diabetes; Women; Italy; Retinopathy; Cardiovascular diseases; Type 1 diabetes; MicroRNAs
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-021-03142-4

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). 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. 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. 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.