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

Federica Barutta*, Beatrice Corbetta, Stefania Bellini, Simonetta Guarrera, Giuseppe Matullo, Michela Scandella, Casper Schalkwijk, Coen D. Stehouwer, Nishi Chaturvedi, Sabita S. Soedamah-Muthu, Marilena Durazzo, Gabriella Gruden

*Corresponding author for this work

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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.
Original languageEnglish
Article number475
Number of pages10
JournalJournal of Translational Medicine
Volume19
DOIs
Publication statusPublished - 2021

Keywords

  • Cardiovascular diseases
  • DISEASE
  • EXTRACELLULAR VESICLES
  • IMMUNE
  • INFLAMMATION
  • MIR-146A
  • MicroRNAs
  • PATHOGENESIS
  • PERIPHERAL NEUROPATHY
  • PROGRESSION
  • RISK
  • Retinopathy
  • SUPPRESSION
  • Type 1 diabetes

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