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Review
. 2023 Mar 24;24(7):6186.
doi: 10.3390/ijms24076186.

Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus-A Systematic Review and Meta-Analysis

Sofie Dinesen  1 , Alisar El-Faitarouni  1 , Nanna Lond Skov Frisk  1 , Anja Elaine Sørensen  1   2 , Louise Torp Dalgaard  1
Affiliations
Review

Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus-A Systematic Review and Meta-Analysis

Sofie Dinesen et al. Int J Mol Sci. .

Abstract

Gestational diabetes mellitus (GDM) is a severe pregnancy complication for both the woman and the child. Women who suffer from GDM have a greater risk of developing Type 2 diabetes mellitus (T2DM) later in life. Identification of any potential biomarkers for the early prediction of gestational diabetes can help prevent the disease in women with a high risk. Studies show microRNA (miRNA) as a potential biomarker for the early discovery of GDM, but there is a lack of clarity as to which miRNAs are consistently altered in GDM. This study aimed to perform a systematic review and meta-analysis to investigate miRNAs associated with GDM by comparing GDM cases with normoglycemic controls. The systematic review was performed according to PRISMA guidelines with searches in PubMed, Web of Science, and ScienceDirect. The primary search resulted in a total of 849 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 35 full-text articles, which were evaluated for risk of bias and estimates of quality, after which data were extracted and relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: MiR-29a, miR-330, miR-134, miR-132, miR-16, miR-223, miR-155, miR-122, miR-17, miR-103, miR-125, miR-210, and miR-222. While some miRNAs showed considerable between-study variability, miR-29a, miR-330, miR-134, miR-16, miR-223, and miR-17 showed significant overall upregulation in GDM, while circulating levels of miR-132 and miR-155 were decreased among GDM patients, suggesting further studies of these as biomarkers for early GDM discovery.

Keywords: diagnostic biomarker; gestational diabetes; microRNA; prognostic biomarker.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 6
Figure 6
Forest plots of the fixed-effect meta-analysis of (A) miR-17 [30,33,37], (B) miR-103 [16,20,21], (C) miR-125a/b [18,37,52], (D) miR-210 [28,33,41], and (E) miR-222 [18,28,29,51].
Figure 1
Figure 1
PRISMA flow diagram showing the search and inclusion numbers of the systematic review.
Figure 2
Figure 2
Quality evaluations of the included studies according to the NOS Scale. Green scale (right side) corresponds to the percentage of NOS scale points fulfilled, and blue scale (left side) corresponds to the percentage of NOS scale points not fulfilled. References for evaluated studies: Pfeiffer et al. (2020) [16], Ke et al. (2022) [17], Zhao et al. (2011) [18], Ye et al. (2022) [19], Sørensen et al. (2022) [20], Sørensen et al. (2021) [21], Juchnicka et al. (2022) [22], Abdeltawab et al. (2022) [23], Stirm et al. (2018) [24], Peng et al. (2018) [25], Zhang et al. (2021) [26], Wei et al. (2021) [27], Wander et al. (2017) [28], Radojičić et al. (2022) [29], Martinez-Ibarra et al. (2019) [9], Cao et al. (2017) [30], Yoffe et al. (2019) [31], Nair et al. (2018) [32], Hromadnikova et al. (2022) [33], Tagoma et al. (2018) [34], Niu et al. (2022) [35], Nair et al. (2021) [36], Lamadrid-Romero et al. (2018) [37], Zhou et al. (2019) [38], Yu et al. (2021) [39], Wang et al. (2021) [40], Gillet et al. (2019) [41], Li et al. (2021) [42], Hocaoglu et al. (2019) [43], Wen et al. (2021) [44], Shen et al. (2021) [45], Bhushan et al. (2022) [46], Xiao et al. (2020) [47], Zhang et al. (2020) [48].
Figure 3
Figure 3
Diversity in the reported circulating miRNAs investigated in relation to GDM pregnancies. Twenty-two miRNAs were reported to be investigated in three or more original studies, while the majority of investigated miRNAs (n = 92 miRNA species) were only investigated in one original study.
Figure 4
Figure 4
Forest plots of the fixed-effect meta-analysis of (A) miR-29a [9,18,20,21,28,33,41], (B) miR-330 [9,16,20,21,47], (C) miR-134 [17,20,21], and (D) miR-132 [18,38,41].
Figure 5
Figure 5
Forest plots of the fixed-effect meta-analysis of (A) miR-16 [9,20,21,22,30,33,36,43], (B) miR-223 [20,21,23,28,31], (C) miR-155 [28,33,43], and (D) miR-122 [19,20,21,41].
Figure 7
Figure 7
Overall temporal regulation of the circulating levels of miR-16-5p throughout gestation: (A) Circulating levels of miR-16-5p at <20 weeks, 20–28 weeks, and 35–40 weeks of gestation, plotted for Cao et al., 2017 [30], Sørensen et al., 2021 [21], Nair et al., 2018 [52], and Sørensen et al., 2022 [20], calculated relative to levels in nondiabetic control women matched for gestational age. (B) Main-effects meta-analysis for circulating levels of miR-16-5p at gestational weeks 20–28.
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