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

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.

Pediatric reference values of carotid-femoral pulse wave velocity determined with an oscillometric device.

BACKGROUND: A semi-automated devise for oscillometric measurement (Vicorder) of carotid-femoral pulse wave velocity (cfPWV) has been considered to be especially suited for multicenter studies in children and adolescents. METHODS: Within a healthy pediatric population (156 boys/158 girls; mean age 10.8 years, range 5.0-19.6 years), the transit time of the pulse wave was measured oscillometrically (Vicorder) between a carotid and femoral cuff. For calculation of cfPWV, the traveled path length was set to 80% of the direct distance between both sites of measurement. Reference tables were generated using the maximum-likelihood curve-fitting technique and SD scores were calculated. Normalizing the same set of data with reference values specific for applanation tonometry yielded Z(at)values. Effects of sex, age, height, weight, BMI, blood pressure (BP), and heart rate on cfPWV as well as the correlation between sex-specific age-related and height-related Z(osci) and Z(at)were investigated. RESULTS: Sex-specific reference values and curves for cfPWV as a function of age and height are presented. cfPWV correlated positively with age, height, weight, SBP, mean arterial BP, and sex (each P  <  0.005). Multiple regression analysis identified age, sex, and mean arterial pressure as significant independent predictors of cfPWV explaining 42% of the overall variability. Strong linear relationships between Z(osci) and Z(at) were noted and per sex a set of age and height-related equation for conversion was derived: Z(at),age  = -0.22 + 0.68 × Z(osci),age; r  =  0.98 and Z(at),height  = -0.33 + 0.66 × Z(osci),height; r  =  0.99 in boys and Z(at),age  = -0.61 + 0.81 × Z(osci),age; r  =  0.98 and Z(at),height  = -0.73 + 0.72 × Z(osci),height; r  =  0.97 in girls (each P  <  0.001). CONCLUSION: A strong linear association between height-related oscillometric and tonometric Z-scores was observed. Age-related Z-scores are of limited value when comparing results across different populations and methods.