Circulating miR-30a-5p and miR-182-5p in Prediabetes and Screen-Detected Diabetes Mellitus

Cecil Jack Weale; Don M Matshazi; Saarah F G Davids; Shanel Raghubeer; Rajiv T Erasmus; Andre Pascal Kengne; Glenda Mary Davison; Tandi E Matsha

doi:10.2147/DMSO.S286081

Circulating miR-30a-5p and miR-182-5p in Prediabetes and Screen-Detected Diabetes Mellitus

Diabetes Metab Syndr Obes. 2020 Dec 21:13:5037-5047. doi: 10.2147/DMSO.S286081. eCollection 2020.

Authors

Cecil Jack Weale¹, Don M Matshazi¹, Saarah F G Davids¹, Shanel Raghubeer¹, Rajiv T Erasmus², Andre Pascal Kengne^{3

4}, Glenda Mary Davison¹, Tandi E Matsha¹

Affiliations

¹ SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town, South Africa.
² Division of Chemical Pathology, Faculty of Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town, South Africa.
³ Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa.
⁴ Department of Medicine, University of Cape Town, Cape Town, South Africa.

Abstract

Background: microRNAs (miRNAs) have been touted as potential diagnostic and prognostic biomarkers for various diseases. The aim of the present study was to evaluate the diagnostic value of miR-30a-5p and miR-182-5p for prediabetes and screen-detected type 2 diabetes mellitus (T2DM).

Methods: The study included 1270 participants (207 prediabetes, 94 screen-detected diabetes and 969 normotolerant) from the Vascular and Metabolic Health (VMH) study. Whole blood levels of miR-30a-5p and miR-182-5p were quantitated by RT-qPCR. Multivariable logistic regressions were used to relate miRNAs with prediabetes or T2DM and receiver operating characteristic (ROC) curves were used to evaluate the ability of each miRNA to diagnose these conditions.

Results: Both miRNAs were significantly highly expressed in individuals with prediabetes or T2DM (both ≥3.2-fold, and p<0.001). We also observed significant under-expression in T2DM relative to prediabetes for miR-182-5p (0.49-fold, p=0.001). Age, sex and BMI-adjusted partial correlation coefficient analysis revealed a significant correlation between the two miRNAs across glucose tolerance statuses (r≥0.932, p<0.001). In normotolerant individuals, both miRNAs showed a negative correlation with waist circumference and positive correlation with HDL-cholesterol whilst in T2DM they correlated positively with hip circumference, 2-hour insulin, HDL- and LDL-cholesterol. Multivariable logistic regressions revealed both miRNAs to be consistently and continuously associated with prediabetes or T2DM (OR≥1.18, 95% 95% CI: 1.10-1.28, p<0.001), while only miR-182-5p associated with a reduced prevalence of T2DM relative to prediabetes (OR: 0.89, 95% CI: 0.83-0.96, p=0.003). In ROC analyses, miR-182-5p almost outperformed HbA1c in diagnosing prediabetes; area under the curve 0.74 vs 0.69.

Conclusion: Our findings demonstrate that miR-30a-5p and miR-182-5p are associated with dysglycaemia and could potentially predict prediabetes, particularly miR-182-5p.

Keywords: Africa; diabetes; miR-182-5p; miR-30a-5p; prediabetes.

Grants and funding

This research project was supported by grants from the South African Medical Research Council (SAMRC), with funds from National Treasury under its Economic Competitiveness and Support Package (MRC-RFA-UFSP-01-2013/VMH Study), South African National Research Foundation (SANRF) (Grant no. 115450). Any opinions, findings, conclusions or recommendations expressed in this article are those of the author(s), and the SAMRC and/or SANRF do not accept any liability in this regard.