SAMRC/CPUT Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Cape Town, South Africa.
J Diabetes Investig. 2024 Oct;15(10):1377-1389. doi: 10.1111/jdi.14278. Epub 2024 Aug 1.
This study aims to investigate miR-486-5p and miR-novel-chr1_40444 expressions in dysglycemic individuals. Validating RNA-sequencing findings in a larger sample via reverse transcription qPCR (RT-qPCR), we aim to address global diagnostic and screening limitations, using an African cohort as an example.
This cross-sectional study involved 1,271 individuals [normoglycemic (n = 974), prediabetic (n = 206), screen-detected type 2 diabetes (n = 91)] from the ongoing Vascular and Metabolic Health (VMH) study in Cape Town, South Africa. Whole blood miRNA expression was assessed using TaqMan-based RT-qPCR, with data normalized to an endogenous control (miR-16-5p).
Significant underexpression was observed in prediabetes vs normoglycemia for miR-486-5p (P = 0.038), whilst both miRNAs demonstrated significant upregulation in screen-detected type 2 diabetes vs normoglycemia (miR-486-5p, P = 0.009; miR-novel-chr1_40444, P < 0.001), and screen-detected type 2 diabetes in comparison with prediabetes (miR-486-5p, P < 0.001; miR-novel-chr1_40444, P < 0.001). Multivariable regression analyses revealed pronounced interrelations between miR-novel-chr1_40444 and screen-detected type 2 diabetes in unadjusted and adjusted models (Model 1: P < 0.001, Model 2: P < 0.001, Model 3: P = 0.030). Moreover, receiver operating characteristic (ROC) curves revealed significantly enhanced diagnostic capabilities for screen-detected type 2 diabetes vs either normoglycemia (AUC = 0.971, P < 0.001), non-diabetes (AUC = 0.959, P < 0.001), or prediabetes (AUC = 0.902, P < 0.001) when combining the miRNAs with 2 h postprandial glucose.
This study demonstrated the enhanced power of incorporating miRNAs with traditional markers in distinguishing screen-detected type 2 diabetes, warranting further investigations on their unique role in the development of type 2 diabetes.
本研究旨在探讨糖代谢异常个体中 miR-486-5p 和 miR-novel-chr1_40444 的表达。通过逆转录 qPCR(RT-qPCR)在更大的样本中验证 RNA 测序结果,我们旨在利用非裔人群作为范例,解决全球诊断和筛查的局限性。
这项横断面研究纳入了来自南非开普敦正在进行的血管和代谢健康(VMH)研究中的 1271 名个体[血糖正常(n=974)、糖尿病前期(n=206)、筛查发现的 2 型糖尿病(n=91)]。采用 TaqMan 基于 RT-qPCR 检测全血 miRNA 表达,数据以内参(miR-16-5p)标准化。
与血糖正常相比,糖尿病前期 miR-486-5p 表达明显下调(P=0.038),而这两种 miRNA 在筛查发现的 2 型糖尿病中均显著上调(miR-486-5p,P=0.009;miR-novel-chr1_40444,P<0.001),与糖尿病前期相比,筛查发现的 2 型糖尿病也上调(miR-486-5p,P<0.001;miR-novel-chr1_40444,P<0.001)。多变量回归分析显示,miR-novel-chr1_40444 与未经调整和调整模型中的筛查发现的 2 型糖尿病之间存在显著的相互关系(模型 1:P<0.001,模型 2:P<0.001,模型 3:P=0.030)。此外,接受者操作特征(ROC)曲线显示,与血糖正常(AUC=0.971,P<0.001)、非糖尿病(AUC=0.959,P<0.001)或糖尿病前期(AUC=0.902,P<0.001)相比,将这两种 miRNA 与餐后 2 小时血糖相结合,对筛查发现的 2 型糖尿病的诊断能力显著增强。
本研究表明,将 miRNA 与传统标志物结合起来区分筛查发现的 2 型糖尿病具有更强的效能,这证明了进一步研究其在 2 型糖尿病发展中的独特作用是有必要的。