Investigating the altered expression of miR-486-5p and miR-novel-chr1_40444 in dysglycemia in a South African population

Aims: 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. Materials and Methods: 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). Results: 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. Conclusions: 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.