title: Decreased serum level of miR-146a as sign of chronic inflammation in type 2 diabetic patients.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Immunology, Central University of Ecuador, Quito, Ecuador.
authors.forename: Lucy
authors.initials: L
authors.lastname: Baldeón R
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Weigelt
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: de Wit
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Behiye
authors.initials: B
authors.lastname: Ozcan
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Adri
authors.initials: A
authors.lastname: van Oudenaren
authors.affiliation: Department of Immunology, Central University of Ecuador, Quito, Ecuador.
authors.forename: Fernando
authors.initials: F
authors.lastname: Sempértegui
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Sijbrands
authors.affiliation: Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Grosse
authors.affiliation: Institute of Research in Health and Nutrition, University San Francisco de Quito, Quito, Ecuador.
authors.forename: Wilma
authors.initials: W
authors.lastname: Freire
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Prometeo Program SENESCYT, Central University of Ecuador and Universidad de las Fuerzas Armadas, Quito, Ecuador.
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; C542542:MIRN146 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs