Dataset Information

Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus.

ABSTRACT:

Aims/introduction

Differentially expressed microribonucleic acids (miRNAs) in the placenta and circulating exosomes are of diagnostic value for gestational diabetes mellitus (GDM). In a cross-sectional study, we identified miRNAs expressed both in the placenta and circulating exosomes of pregnant women with GDM, and estimated their diagnostic value.

Materials and methods

Next-generation sequencing was used to identify miRNAs in the placenta that were differentially expressed between GDM and normal glucose tolerance pregnancies. Quantitative polymerase chain reaction was used to validate the identified targets. Western blot and transmission electron microscopy were used to validate exosomes. Univariate logistic regression analysis was used to establish diagnostic models based on miRNAs expression, and the diagnostic value was estimated using the receiver operator characteristic curve.

Results

We identified 157 dysregulated miRNAs in the placental tissue obtained from GDM pregnancies. Of these, miRNA-125b was downregulated (P < 0.001), whereas miRNA-144 was upregulated (P < 0.001). The patterns of these two miRNAs remained the same in circulating exosomes from GDM pregnancies (all P < 0.001). miRNA-144 levels in the circulating exosomes negatively correlated with body mass index both before pregnancy (P = 0.018) and before delivery (P = 0.039), and positively correlated with blood glucose at 1 h, estimated using the oral glucose tolerance test (P = 0.044). The area under curve for the established diagnostic model was 0.898, which was higher than blood glucose levels at 0 h.

Conclusions

These findings suggest that miRNA-125b and miRNA-144 are consistently dysregulated in circulating exosomes and the placenta from GDM pregnancies, and are of excellent diagnostic value for GDM.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8354507 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe micronutrient iodine is essential for a healthy intrauterine environment and is required for optimal fetal growth and neurodevelopment. Evidence linking urinary iodine concentrations, which mainly reflects short-term iodine intake, to gestational diabetes mellitus (GDM) is inconclusive. Although the placental concentrations would better reflect the long-term gestational iodine status, no studies to date have investigated the association between the placental iodine load and the risk at GDM. Moreover, evidence is lacking whether placental iodine could play a role in biomarkers of insulin resistance and β-cell activity.MethodsWe assessed the incidence of GDM between weeks 24 and 28 of gestation for 471 mother-neonate pairs from the ENVIRONAGE birth cohort. In placentas, we determined the iodine concentrations. In maternal and cord blood, we measured the insulin concentrations, the Homeostasis Model Assessment (HOMA) for insulin resistance (IR) index, and β-cell activity. Logistic regression was used to estimate the odds ratios (OR) of GDM, and the population attributable factor (PAF) was calculated. Generalized linear models estimated the changes in insulin, HOMA-IR, and β-cell activity for a 5 μg/kg increase in placental iodine.ResultsHigher placental iodine concentrations decreased the risk at GDM (OR = 0.82; 95%CI 0.72 to 0.93; p = 0.003). According to the PAF, 54.2% (95%CI 11.4 to 82.3%; p = 0.0006) of the GDM cases could be prevented if the mothers of the lowest tertile of placental iodine would have placental iodine levels as those belonging to the highest tertile. In cord blood, the plasma insulin concentration was inversely associated with the placental iodine load (β = - 4.8%; 95%CI - 8.9 to - 0.6%; p = 0.026).ConclusionsHigher concentrations of placental iodine are linked with a lower incidence of GDM. Moreover, a lower placental iodine load is associated with an altered plasma insulin concentration, HOMA-IR index, and β-cell activity. These findings postulate that a mild-to-moderate iodine deficiency could be linked with subclinical and early-onset alterations in the normal insulin homeostasis in healthy pregnant women. Nevertheless, the functional link between gestational iodine status and GDM warrants further research.