Diabetes-associated microRNAs in pediatric patients with type 1 diabetes mellitus: a cross-sectional cohort study

J Clin Endocrinol Metab. 2014 Sep;99(9):E1661-5. doi: 10.1210/jc.2013-3868. Epub 2014 Jun 17.

Abstract

Context: 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.

Design: 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.

Setting: The study consisted of clinical pediatric patients with type 1 diabetes.

Patients or other participants: 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.

Main outcome measure(s): 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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Biomarkers / blood
  • Biomarkers / urine
  • Child
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / genetics*
  • Down-Regulation / genetics
  • Female
  • Humans
  • Hyperglycemia / diagnosis
  • Hyperglycemia / genetics
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / urine
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • MIRN126 microRNA, human
  • MIRN21 microRNA, human
  • MIRN219 microRNA, human
  • MicroRNAs