Osipova Julia, Fischer Dagmar-Christiane, Dangwal Seema, Volkmann Ingo, Widera Christian, Schwarz Katrin, Lorenzen Johan M, Schreiver Corinna, Jacoby Ulrike, Heimhalt Mirjam, Thum Thomas, Haffner Dieter
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.
J Clin Endocrinol Metab. 2014 Sep;99(9):E1661-5. doi: 10.1210/jc.2013-3868. Epub 2014 Jun 17.
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.
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.
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.
The study consisted of clinical pediatric patients with type 1 diabetes.
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.
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.
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.
循环微RNA(miRNA/miR)被用作疾病的新型生物标志物。已知在糖尿病条件下,miR-21、miR-126和miR-210在体内或体外会发生失调。
本研究旨在调查1型糖尿病儿科患者血浆和尿液中的循环miR-21、miR-126和miR-210,并将我们的研究结果与1型糖尿病儿童的心血管和糖尿病肾病危险因素联系起来。
采用定量逆转录聚合酶链反应(RT-PCR)检测68例1型糖尿病儿科患者和79例年龄及性别匹配的对照者的血浆和尿液样本中miR-21、miR-126和miR-210的浓度。
该研究纳入临床1型糖尿病儿科患者。
患者的纳入标准为确诊为1型糖尿病。排除标准为过去3个月内有发热性疾病;慢性炎症或风湿性疾病;肝炎;艾滋病毒;糖皮质激素治疗;肝、肾或心力衰竭;或遗传性血脂异常。患者的年龄和性别与对照者匹配。
主要观察参数为1型糖尿病患者血浆和尿液中miR-21、miR-126和miR-210浓度与相应对照相比的变化。
1型糖尿病患者血浆和尿液中miR-21和miR-210的循环miRNA水平显著上调。糖尿病患者尿液中的miR-126水平显著低于年龄和性别匹配的对照者,且患者糖化血红蛋白平均值与miR-126浓度值呈负相关。相比之下,两个队列中血浆中循环miR-126水平相当。对于尿液miR-21,我们通过调整后的受试者工作特征曲线分析发现曲线下面积为0.78。
1型糖尿病儿科患者血浆和尿液样本中miR-21、miR-126和miR-210存在显著失调,这可能表明糖尿病相关疾病的早期发病。