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.

Circulating microRNAs from early childhood and adolescence are associated with pre-diabetes at 18 years of age in women from the PMNS cohort

“…22 MicroRNA-192 and -193b are reported to be significantly higher in pre-diabetes stage and return to lower levels following exercise. 23 The majority of microRNAs reported to be dysregulated in pre-diabetes through these studies [20][21][22][23] are also seen to be differentially expressed in our analysis (including miR-30e, miR-223, miR-126, miR-150 and miR-193b) (Fig. 1B).…”

Relationship of miRNA‑126 and miRNA‑122 expression with type 2 diabetes mellitus and related glucose metabolism parameters: A systematic review and meta‑analysis

“…Although increasing studies have been performed to examine the potential associations of miR-126 and miR-122 expression with T2DM and related glucose metabolism parameters, inconsistent results of existing studies remained. For example, evidence has shown a lower expression level of miR-126 in prevalent T2DM compared with healthy controls (6,11,17), whereas one recent study published in 2021 indicated that miR-126-3p was positively associated with T2DM risk and higher FBG level (18). Therefore, this meta-analysis systematically and quantitatively evaluated the relationship between circulating miR-126 and miR-122 expression levels and the risks of T2DM as well as related glucose metabolism parameters.…”

Circulating Nucleic Acid-Based Biomarkers of Type 2 Diabetes

“…This miRNA is highly enriched in endothelial cells and is important for angiogenesis and wound repair [ 107 ]. It is down-regulated in T2D patients compared to non-diabetic controls and those with impaired glucose tolerance [ 62 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ]. It is also further down-regulated in T2D patients with complications [ 111 , 115 , 119 ] and increases after six months of treatment (insulin with diet control and exercise) [ 116 ].…”