Journal of Diabetes Investigation (Oct 2024)

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

  • Cecil J Weale,
  • Chanelle Schroeder,
  • Don M Matshazi,
  • Saarah FG Davids,
  • Rajiv T Erasmus,
  • Andre P Kengne,
  • Glenda M Davison,
  • Tandi E Matsha

DOI
https://doi.org/10.1111/jdi.14278
Journal volume & issue
Vol. 15, no. 10
pp. 1377 – 1389

Abstract

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Abstract 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.

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