Investigation of MicroRNAs that can differentiate between pre-diabetes and diabetes

NHREC: REC - 230 408 – 014 and N14/01/003

Background: An ever-increasing incidence of Type 2 Diabetes Mellitus (T2DM) in the global population, has caused a public health concern. MicroRNA are small non-coding RNAs which control gene expression and are involved in several pathophysiological processes, therefore allowing them (miRNA) to play a role in disease detection. The scarcity of studies which investigates the role of miRNA in T2DM, especially in a South African population, has encouraged studies such as the preliminary study conducted by Matsha et al. (2018), profiling miRNA in 1989 randomly selected participants where they found that the expression of hsa-miR-486-5p and hsa-miR-novel-chr1_40444 were 2 of the most dysregulated miRNA in individuals with screen detected Type 2 diabetes mellitus (DM), in comparison to those individuals who were either on treatment or were normoglycaemic. This current study further investigates and validates the expression of hsa-miR-486-5p and hsa-miR-novel-chr1_40444 in 1459 participants of the sample cohort who have participated in the miRNA profiling study.

Methods: The Quantum Studio 7 (Life Technologies, USA) was used to perform quantitative reverse-transcription PCR (RT-qPCR) on 1459 whole blood samples provided by participants who partook in the Vascular and Metabolic Health study. All the participants underwent anthropometric measurements, and biochemical parameters were measured at an accredited pathology laboratory. Participant glycaemic status was determined using the oral glucose tolerance test (OGTT).

Results: Hsa-miR-486-5p and hsa-miR-novel-chr1_40444 were significantly overexpressed in diabetics compared to both controls, and prediabetics (all p≤ 0.001). Moreover, multivariate regression analysis revealed independent associations between the expression of both miRNAs and the risk of diabetes, with significant retained in unadjusted and adjusted models (all p≤0.001).

Conclusion: This study has demonstrated the potential capabilities of hsa-miR-486-5p and hsa-miR-novel-chr1_40444 in distinguishing between Type 2 diabetes (both newly-diagnosed and known diabetes) from normoglycaemia and early-stage hyperglycaemia (pre-diabetes). However, further investigation is required.

REC Approval Reference No: CPUT/HW-REC 2019/H3, CPUT/HW-REC 2019/H3