MicroRNAs-1299, -126-3p and -30e-3p as Potential Diagnostic Biomarkers for Prediabetes

Abstract

This cross-sectional study investigated the association of miR-1299, -126-3p and -30e-3p with and their diagnostic capability for dysglycaemia in 1273 (men, n = 345) South Africans, aged >20 years. Glycaemic status was assessed by oral glucose tolerance test (OGTT). Whole blood microRNA (miRNA) expressions were assessed using TaqMan-based reverse transcription quantitative-PCR (RT-qPCR). Receiver operating characteristic (ROC) curves assessed the ability of each miRNA to discriminate dysglycaemia, while multivariable logistic regression analyses linked expression with dysglycaemia. In all, 207 (16.2%) and 94 (7.4%) participants had prediabetes and type 2 diabetes mellitus (T2DM), respectively. All three miRNAs were significantly highly expressed in individuals with prediabetes compared to normotolerant patients, p < 0.001. miR-30e-3p and miR-126-3p were also significantly more expressed in T2DM versus normotolerant patients, p < 0.001. In multivariable logistic regressions, the three miRNAs were consistently and continuously associated with prediabetes, while only miR-126-3p was associated with T2DM. The ROC analysis indicated all three miRNAs had a significant overall predictive ability to diagnose prediabetes, diabetes and the combination of both (dysglycaemia), with the area under the receiver operating characteristic curve (AUC) being significantly higher for miR-126-3p in prediabetes. For prediabetes diagnosis, miR-126-3p (AUC = 0.760) outperformed HbA1c (AUC = 0.695), p = 0.042. These results suggest that miR-1299, -126-3p and -30e-3p are associated with prediabetes, and measuring miR-126-3p could potentially contribute to diabetes risk screening strategies.

Keywords: Africa; biomarker; diabetes; microRNA (miRNA); prediabetes.

Figure 1

Relative Expression of miR-1299, miR-30e-3p and miR-126-3p according to glycaemic status. The expression of the microRNAs (miRNAs) was normalised to the relative expression of miR-16-5p. (A): miR-1299. (B): miR-30e-3p. (C): miR-126-3p. Data are shown as mean ± SD. n, normotolerant; D, diabetes; p, prediabetes.

Figure 2

Receiver operating characteristic (ROC). ROCs were constructed for each miRNA to evaluate their diagnostic value for prediabetes, diabetes, dysglycaemia as positive cases and normotolerant people as negative cases, as well as for diabetes as positive cases and prediabetes as negative cases. (A): Dysglycaemia vs. normotolerant (B): Prediabetes vs. normotolerant (C): T2DM vs. normotolerant (D): Prediabetes vs T2DM.