Department of Endocrinology, Provincial Hospital/Shandong University, 324 Jingwu Road, Jinan, People's Republic of China.
Acta Diabetol. 2011 Mar;48(1):61-9. doi: 10.1007/s00592-010-0226-0. Epub 2010 Sep 21.
To explore the clinical significance of seven diabetes-related serum microRNAs (miR-9, miR-29a, miR-30d, miR34a, miR-124a, miR146a and miR375) during the pathogenesis of type 2 diabetes (T2D), 56 subjects were recruited to this study: 18 cases of newly diagnosed T2D (n-T2D) patients, 19 cases of pre-diabetes individuals (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) and 19 cases of T2D-susceptible individuals with normal glucose tolerance (s-NGT). Serum miRNAs were determined by real-time RT-PCR. Expression levels of single miRNAs and the expression signatures of miRNAs as a panel were analysed among the three groups. In n-T2D, all 7 miRNAs were significantly up-regulated compared with s-NGT and five were significantly up-regulated compared with pre-diabetes, while miRNA expression was not significantly different between s-NGT and pre-diabetes. By Canonical discriminant analysis, 70.6% of n-T2D subjects (12/17) were recognized by canonical discriminant function, while s-NGT and pre-diabetes subjects could not be discriminated from each other. Similar results were found in Hierarchical Clustering analysis based on the expression levels of all seven miRNAs. In different statistical analysis, miR-34a always showed the most significant differences. We conclude that the expression levels of seven diabetes-related miRNAs in serum were significantly elevated in n-T2D compared with pre-diabetes and/or s-NGT, and the latter two groups featured similar expression patterns of these miRNAs, suggesting that during the pathogenesis of T2D, the peripheral diabetes-related miRNAs have not changed significantly from s-NGT at pre-diabetic stage.
为了探讨七种糖尿病相关血清 microRNAs(miR-9、miR-29a、miR-30d、miR-34a、miR-124a、miR-146a 和 miR-375)在 2 型糖尿病(T2D)发病机制中的临床意义,招募了 56 名受试者:18 例新诊断的 T2D(n-T2D)患者,19 例糖尿病前期个体(糖耐量受损[IGT]和/或空腹血糖受损[IFG])和 19 例 T2D 易感个体(血糖正常的耐糖量[s-NGT])。采用实时 RT-PCR 测定血清 microRNAs。分析了三组之间单个 microRNA 的表达水平和 microRNA 作为一组的表达特征。在 n-T2D 中,与 s-NGT 相比,所有 7 种 microRNA 均显著上调,与 pre-diabetes 相比,有 5 种 microRNA 显著上调,而 s-NGT 与 pre-diabetes 之间的 microRNA 表达无显著差异。通过典型判别分析,17 例 n-T2D 患者中有 70.6%(12/17)被典型判别函数识别,而 s-NGT 和 pre-diabetes 患者不能相互区分。基于所有七种 microRNAs 的表达水平的层次聚类分析也得到了类似的结果。在不同的统计分析中,miR-34a 始终表现出最显著的差异。我们得出结论,与 pre-diabetes 和/或 s-NGT 相比,n-T2D 患者血清中七种糖尿病相关 microRNA 的表达水平显著升高,后两组 microRNA 的表达模式相似,提示在 T2D 发病机制中,外周糖尿病相关 microRNA 在 pre-diabetic 阶段与 s-NGT 相比没有明显变化。