Diabetes-Associated MicroRNAs in Pediatric Patients With Type 1 Diabetes Mellitus: A Cross-Sectional Cohort Study
Diabetes-Associated MicroRNAs in Pediatric Patients With Type 1 Diabetes Mellitus: A Cross-Sectional Cohort Study
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DOI：
10.1210/jc.2013-3868
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发表时间：
2014-09-01
影响因子：
5.8
通讯作者：
Haffner, Dieter
中科院分区：
文献类型：
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作者：
Osipova, Julia;Fischer, Dagmar-Christiane;Haffner, Dieter
循环microRNAs（miRNAs/miRs）被用作疾病的新生物标志物。miR-21、miR-126和miR-210已知在体内或体外糖尿病条件下是去调节的。目的：本研究的目的是调查1型糖尿病儿童患者血浆和尿液中循环的miR-21、miR-126和miR-210，并将我们的发现与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。设计：采用定量RT-PCR检测68例1型糖尿病患儿和79例性别和年龄匹配的对照组的血浆和尿液样本中miR-21、miR-126和miR-210的浓度。排除标准为过去3个月内的发热性疾病;慢性炎症或风湿性疾病;肝炎; HIV;糖皮质激素治疗;肝、肾或心力衰竭;或遗传性血脂异常。结果：1型糖尿病患者的血浆和尿液中miR-21和miR-210的循环miRNA水平显著上调。糖尿病患者的尿miR-126水平显著低于年龄和性别匹配的对照组，并且患者的糖化血红蛋白平均值与miR-126浓度值呈负相关。相比之下，两个队列中血浆中的循环miR-126水平相当。结论：1型糖尿病患儿血浆和尿液中miR-21、miR-126和miR-210的表达明显失调，提示糖尿病相关疾病的早期发生。
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.