Table 1 Previous studies on dynamics of the most common significantly dysregulated miRNA in pregnant women with GDM
From: Exploring the potential of microRNA as a diagnostic tool for gestational diabetes
Population ethnicity | GDM diagnostic criteria | Gestational age at miRNA detection | Sample size | Type of sample | miRNA detection method | Normalization To correct for technical variation | Significantly Dysregulated MiRNA in GDM group and the study findings | Refs. |
|---|---|---|---|---|---|---|---|---|
Mexican (Hispanic/Latino ethnicity is a predisposing factor) | International Association of Diabetes Pregnancy Study Group (IADPSG) | 16–19 weeks | 40 (GDM = 18, control = 22) | Serum | Real-Time PCR System | miR-454 | -Higher expression of miR-9-5p, miR-29a-3p and miR-330-3p No significant difference of miR-16-5p expression | [30] |
Chinese | NA | 24–28 weeks | (GDM = 85, control = 72) | Plasma | Real-Time PCR System | Caenorhabditis elegans (C. elegans) microRNAs (cel-miR-39, cel-miR-54, and cel-miR-238) | microRNA-16-5p, -17-5p and 20a-5p were significantly upregulated | [31] |
Chinese | American Diabetes Association (ADA) | 16-19 weeks | (GDM = 10, control = 10) | Plasma | high-throughput sequencing technology | Digital Gene Expression II and validated by qRT-PCR | miR-16-5p, miR17-5p, miR-19a-3p, miR-19b-3p and miR-20a-5p were significantly upregulated | [46] |
Poland | World Health Organization (WHO) criteria | 9–12 weeks | (GDM = 24, control = 24) | Serum | NanoString technology | average geometric mean of the top 100 probes detected | microRNA-16-5p, miR-142-3p and miR-144-3p were significantly upregulated | [32] |
European | IADPSG/WHO2013 criteria | baseline ≤ 19 ± 6 days 24–28 weeks 35–37 weeks | obese women with GDM (n = 41), control (n = 41) | Serum | ViiA real-time PCR System | Caenorhabditis elegans (cel)-miR-39, ath-miR-159) and the endogenous small nuclear U6 | Initially significant increase of miR-433-3p while levels of miR-122-5p, -223-3p and -16-5p were significantly higher in the GDM group by the third trimester | [33] |
Chinese | NA | 24–28 weeks | GDM (n = 100) Control (n = 100) | Serum | Quantitative real-time PCR (qPCR) | the endogenous small nuclear U6 | 4.0 fold increase in miRNA-19a and 4.7 mean increase in miRNA-19b expression | [45] |
Caucasian | International Association of the Diabetes and Pregnancy Study Groups (IADPSG) | 24–32 weeks | Screening group: GDM (n = 8) Control (n = 8) Validation group: : GDM (n = 30) Control (n = 30) | WBCs Cord blood | q-PCR | the house keeping gene U6 small nuclear 6 | Significant increase of miRNA-340 marginal increase of 142, miRNA-143 and let-7 g | [34] |
American | American Diabetes Association (ADA) 2004 criteria | 7–23 weeks | GDM (n = 36) controls (n = 80) | Plasma | qRT-PCR | an endogenous housekeeping miRNA, miR-423-3p | miR-155-5p and—21-3p levels were signigicantly increased miR-146b-5p and miR-517-5p were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs (miR-155-5p, -21-3p, -146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses | [35] |
Canadian | guidelines of the Society of Obstetricians and Gynecologists of Canada | 6–15 weeks | GDM (n = 23) controls (n = 46) | extracellular vesicles in serum | Quantitative real-time PCR | the spike-in control synthetic Caenorhabditis elegans miR-39-5p | miR‒122-5p; miR‒132-3p; miR‒1323; miR‒136-5p; miR‒182-3p; miR‒210-3p; miR‒29a-3p; miR‒29b-3p; miR‒342-3p, and miR-520 showed significantly higher levels | [36] |
European | IADPSG/WHO2013 criteria | 15.1 ± 2.4 weeks | GDM (n = 82) controls (n = 41) from obese pregnant women | Serum | qPCR assays | Synthetic Caenorhabditis elegans (cel)-miR-39 was | Elevated miR-16-5p, -29a-3p, and -134-5p levels in women, who were NGT at baseline and later developed GDM | [33] |
Estonian | International Association of Diabetes in Pregnancy Group’s Consensus Panel criteria | 23–31 weeks | GDM (n = 13) Control (n = 9) | plasma | real-time PCR | synthetic C. elegans miR-39 | Significant upregulation of let-7e-5p, let-7 g-5p, miR-100-5p, miR-101-3p, miR-146a-5p, miR-18a-5p, miR-195-5p, miR-222-3p, miR-23b-3p, miR-30b-5p, miR-30c-5p, miR-30d-5p, miR-342-3p, miR-423-5p, miR-92a-3p | [37] |
Chinese European (Indian–Pakistani) (Latin–American)Filipinos | ADIPS and WHO recommendations | < 18 weeks 22–28 weeks 37–40 weeks | Discovery cohort: cases = 15 controls = 14 Validation cohort: cases = 8, control = 14 | Plasma | miRNA sequencing and qRT PCR | housekeeping gene RNU6B | let-7i-5p, miR-10a-5p, miR-151b, miR-16–2-3p, miR-16-5p, miR-1910-5p, -miR-423-5p, miR-92a-3p, miR-92b-3p, miR-563 were significantly upregulated | [68] |
Mexican | American Diabetes Association [ADA] | 1st trimester 2nd trimester 3rd trimester | GDM (n = 67) Control (n = 74) | Serum | q-RT PCR sequencing | synthetic Cel-miR-39-3p | 1st trimester: higher levels of miR-183-5p, -200b-3p 2nd trimester: higher level of miR 125-5p 3rd trimester: higher levels of miR-137 | [72] |
Mexican | WHO criteria | 1st trimester 2nd trimester 3rd trimester | GDM (n = 27) Control (n = 34) | Urine | q-RT PCR | U6 snRNA | significantly higher levels of miR-16-5p, miR-222-3p, miR-516-5p, miR-517-3p and miR-518-5p only in 2nd but not in 3rd trimester | [85] |
Italian | Italian guidelines | 24–33 weeks | Discovery cohort: GDM (n = 4) Control (n = 4) Validation cohort: GDM (n = 21) Control (n = 10) | Plasma | TaqMan miRNA Human Array Panel A platform qRT real-time PCR | the spike-in control ath-miR-159a | miR-330-3p and miR-483-5p were upregulated, miR-548c-3p and miR-532-3p were downregulated | [38] |
Mixed (Spanish and Irish) | the criteria of the National Diabetes Group (NDDG) | third trimester | GDM (n = 31) Control (n = 29) | Serum | qRT real-time PCR | Synthetic C. elegans miRNA (cel-miR-39) spike-in control was added (50 pmol) to each sample for input normalization prior to RNA isolation | miR-330-3p was significantly upregulated which was associated with better response to treatment (diet vs. insulin) | [39] |
Chinese | NA | NA | GDM (n = 48) Control (n = 46) | placenta‐derived mononuclear macrophages | qRT‐PCR | NA | significant increased level of miR‐657 which was correlated with reduced revel of IL‐37 | [92] |
Chinese | the Endocrine Society criteria | after delivery | GDM (n = 15) Control (n = 15) | Placental tissue | miRNA microrarray and real-time PCR (qRT-PCR) | miR-508-3p was up-regulated and miR-27a, miR-9, miR-137, miR-92a, miR-33a, miR-30d, miR-362-5p and miR-502-5p were down-regulated | [95] | |
Chinese | ADA guidelines | 16–19 weeks | -Discovery cohort: GDM (n = 24) Control(n = 24) -Internal Validation cohort: GDM (n = 36) Control(n = 36) -External Validation cohort: GDM (n = 16) Control(n = 16) | Serum | TLDA chip assays and real-time PCR (qRT-PCR) | synthetic C.elegans miR-39 | -miR-132, miR-29a and miR-222 were significantly downregulated - knockdown of miR-29a could increase Insulin induced gene 1 (Insig1) expression level which in turn increase the level of Phosphoenol pyruvate Carboxy Kinase2 (PCK2) in HepG2 cell lines | [97] |
Chinese | NA | beyond 37 weeks | GDM (n = 204) Control(n = 202) | Placenta | qRT-PCR | U6 snRNA | -miR-29b expression was downregulated targeting HIF3A -miR-29b knockdown promoted trophoblast cell migration | [98] |
Chinese | NA | beyond 37 weeks | GDM (n = 166) control(n = 196) | Placenta | tissue microarray in situ hybridization qRT-PCR | U6 snRNA | -miR-30d-5p was significantly down-regulated in GDM placental tissue -in vitro downregulation enhances glucose uptake and regulates HTR8 cells migration and invasion via targeting RAB8A gene | [99] |
South African | International Association of Diabetes and Pregnancy Study Group (IADPSG) | 13–31 weeks | 81 GDM (n = 28) Control (n = 53) | Serum | quantitative real-time PCR | Caenorhabiditis elegans miR-39 | miRNA 20- 5p and miR-222-3p were significantly decreased | [40] |
Chinese | American Diabetes Association | Post delivery | 246 GDM (n = 123) Control (n = 123) | Placenta | quantitative real-time PCR | U6 the housekeeping gene | a significantly lower expression level of miR-96 showing a high sensitivity and specificity | [111] |
Turkish | International Association of Diabetes and Pregnancy Study Groups criteria | 32–33 weeks plus | 69 PCOS (n = 17) GDM (n = 14) PCOS + GDM (n = 11) control (n = 27) | Blood | quantitative real-time PCR | RNU6 | -a significantly upregulated miR-16-5p expression in PCOS patients -a significantly lower expression level of miR-155-5p in GDM patients showing a positive association with BMI and blood glucose levels | [96] |
Chinese | American Diabetes Association (ADA) guidelines | third trimester | GDM (n = 11) control (n = 12) | Plasma | qRT-PCR | NA | significant increase in the expression level of miR-137 that showed to enhance the inflammatory reaction in GDM | [94] |
Chinese | NA | NA | GDM (n = 20) Control(n = 20) | peripheral blood | qRT-PCR | U6 | Significantly lower level miR-494 showing a novel miR-494/PTEN signaling cascade in GDM | [101] |