Serum miR-23a, a potential biomarker for diagnosis of pre-diabetes and type 2 diabetes

Abstract

MicroRNAs (miRNAs) play a crucial role in the pathogenesis of type 2 diabetes (T2D); they regulate several metabolic pathways including insulin secretion, glucose homeostasis, so their potential as biomarkers of diagnosis and prognosis has became increasingly appreciated. In this study, we explore serum miRNA profiles in T2D patients. A total of ten candidate miRNAs were identified by Solexa sequencing scanning and followed by a stem-loop quantitative reverse transcription PCR (qRT-PCR) to assess these candidate serum miRNAs. The results of qRT-PCR assessment revealed low serum levels of miR-23a, let-7i, miR-486, miR-96, miR-186, miR-191, miR-192, and miR-146a in T2D. Except for significantly lower in T2D and pre-diabetes patients compared with normal glucose tolerance (NGT) controls (P = 2.87E-05 and P = 3.75E-02), the levels of miR-23a demonstrated also significant decline in T2D patients compared with pre-diabetes patients (P = 1.06E-02). This marker yielded an AUC of 0.835 (95 % CI 0.717-0.954). At a cutoff value of 1.645, the sensitivity was 79.2 % and the specificity was 75.0 % in discriminating T2D patients from NGT normal controls. These results revealed that serum miR-23a was a valuable biomarker for early detection of T2D and pre-diabetes with NGT.

Circulating microRNAs and diabetes: potential applications in medical practice

“…The observation of the deregulation of miRNA profiles in different biological fluids of diabetic patients compared with healthy controls was the first evidence supporting the idea that miRNAs could be biomarkers of the diabetic disease (Table 1). Indeed, a differential miRNA profile between type 2 diabetic patients and healthy controls was found in whole blood [20,21], serum [22][23][24][25][26], plasma [27][28][29][30][31][32][33] and plasma exosomes [34]. Studies revealed a different miRNA pattern in serum of type 1 diabetic patients compared with healthy individuals [35], as well as in plasma [36,37] and urine [36].…”

“…Interestingly, some reports show that the miRNA profile in plasma or serum is deregulated in the prediabetic state before the development of overt type 2 diabetes. Indeed, type 2 diabetic and prediabetic individuals have a differential profile of circulating miRNAs compared with controls [23,25,30,42]. Interestingly, for some miRNAs, such as miR-126 and miR23a, the difference was significantly greater in type 2 diabetic than in prediabetic individuals, suggesting that their levels could be correlated with the worsening of the glycaemic status [23,25].…”

“…Indeed, type 2 diabetic and prediabetic individuals have a differential profile of circulating miRNAs compared with controls [23,25,30,42]. Interestingly, for some miRNAs, such as miR-126 and miR23a, the difference was significantly greater in type 2 diabetic than in prediabetic individuals, suggesting that their levels could be correlated with the worsening of the glycaemic status [23,25]. Furthermore, in one study miR-192 and miR-193b were reported to be deregulated in the serum of prediabetic individuals but not in that of diabetic individuals, suggesting that prediabetic, diabetic and healthy individuals have distinct profiles [26].…”

“…Urine measurements apply exogenous controls such as miR-39, Uni SP3 or endogenous controls such as RNA U6, while studies based on blood utilise exogenous controls such as miR-39 or endogenous controls such as RNU 6b, RNU 48, RNA U6, miR-16, miR-19b, miR-30c, miR-103, miR-106a, miR-191, miR-146a, miR-221, miR-223, miR-238, miR-423-3p, miR-425, miR-454, or miRNAs belonging to the let-7 family. Although these miRNAs have been selected for their relative stability, the levels of some may vary in diabetic populations such as miR-let-7a [21,34] and miR-let-7f [34], miR-let-7i [25], miR-191 [27,38], miR-223 [27] or miR-146a [22,29,41]. Given these shortcomings, a consensus for data normalisation is urgently needed based, for example, on the geometric mean of a common set of miRNAs.…”

Therapeutic potential of miRNAs in diabetes mellitus

“…Furthermore, a recent study by Yang et al detected significantly lower levels of miR-23a in the serum of T2D patients compared to healthy controls that were already detectable in pre-diabetic individuals 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 8 [66]. A similar type of analysis was also performed in animal models to identify potential biomarkers predicting the development of T1D.…”