title: Diabetes-associated microRNAs in pediatric patients with type 1 diabetes mellitus: a cross-sectional cohort study.
abstract: BACKGROUND
  Circulating microRNAs (miRNAs/miRs) are used as novel biomarkers for diseases. miR-21, miR-126, and miR-210 are known to be deregulated in vivo or in vitro under diabetic conditions.
  
  
  OBJECTIVE
  The aim of this study was to investigate the circulating miR-21, miR-126, and miR-210 in plasma and urine from pediatric patients with type 1 diabetes and to link our findings to cardiovascular and diabetic nephropathy risk factors in children with type 1 diabetes.
  
  
  METHODS
  miR-21, miR-126, and miR-210 concentrations were measured with quantitative RT-PCR in plasma and urine samples from 68 pediatric patients with type 1 diabetes and 79 sex- and age-matched controls.
  
  
  METHODS
  The study consisted of clinical pediatric patients with type 1 diabetes.
  
  
  METHODS
  Inclusion criterion for patients was diagnosed type 1 diabetes. Exclusion criteria were febrile illness during the last 3 months; chronic inflammatory or rheumatic disease; hepatitis; HIV; glucocorticoid treatment; liver, renal, or cardiac failure; or hereditary dyslipidemia. Patients were age and sex matched to controls.
  
  
  METHODS
  Main outcome parameters were changes in miR-21, miR-126, and miR-210 concentration in plasma and urine from type 1 diabetic patients compared with corresponding controls.
  
  
  RESULTS
  Circulating miRNA levels of miR-21 and miR-210 were significantly up-regulated in the plasma and urine of the type 1 diabetic patients. Urinary miR-126 levels in diabetic patients were significantly lower than in age- and gender-matched controls and negatively correlated between the patient's glycated hemoglobin mean and miR-126 concentration value. In contrast, circulating miR-126 levels in plasma were comparable in both cohorts. For urinary miR-21, we found by an adjusted receiver-operating characteristic-curve analysis with an area under the curve of 0.78.
  
  
  CONCLUSIONS
  Type 1 diabetic pediatric patients revealed a significant deregulation of miR-21, miR-126, and miR-210 in plasma and urinary samples, which might indicate an early onset of diabetic-associated diseases.
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (J.O., S.D., I.V., K.S., J.M.L., T.T.), IFB-Tx, Department of Cardiology (C.W.), Department of Paediatric Kidney, Liver, and Metabolic Diseases (D.H.), Hannover Medical School, 30625 Hannover, Germany; Department of Paediatrics (D.-C.F., C.S., U.J., M.H.), University Hospital Rostock, 18051 Rostock, Germany; and National Heart and Lung Institute (T.T.), Imperial College London, London W12 ONN, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Osipova
authors.forename: Dagmar-Christiane
authors.initials: DC
authors.lastname: Fischer
authors.forename: Seema
authors.initials: S
authors.lastname: Dangwal
authors.forename: Ingo
authors.initials: I
authors.lastname: Volkmann
authors.forename: Christian
authors.initials: C
authors.lastname: Widera
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwarz
authors.forename: Johan M
authors.initials: JM
authors.lastname: Lorenzen
authors.forename: Corinna
authors.initials: C
authors.lastname: Schreiver
authors.forename: Ulrike
authors.initials: U
authors.lastname: Jacoby
authors.forename: Mirjam
authors.initials: M
authors.lastname: Heimhalt
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
authors.forename: Dieter
authors.initials: D
authors.lastname: Haffner
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000175:diagnosis / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000652:urine; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C527111:MIRN126 microRNA, human; C524940:MIRN21 microRNA, human; C578248:MIRN219 microRNA, human; D035683:MicroRNAs