Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH) tri-iodethyronine (T3) and L-thyroxine (T4) Hormones had been associated with GDM, but the physiopathological meaning of these alterations is still unclear. Maternal TH cross the placenta through TH Transporters and their Deiodinases metabolize them to regulate fetal TH levels. Currently, the metabolism of TH in placentas with GDM is unknown, and there are no other studies that evaluate the fetal TH from pregnancies with GDM. Therefore, we evaluated the levels of maternal TH during pregnancy, and fetal TH at delivery, and the expression and activity of placental deiodinases from GDM pregnancies. Pregnant women were followed through pregnancy until delivery. We collected blood samples during 10–14, 24–28, and 36–40 weeks of gestation for measure Thyroid-stimulating hormone (TSH), Free T4 (FT4), Total T4 (TT4), and Total T3 (TT3) concentrations from Normal Glucose Tolerance (NGT) and GDM mothers. Moreover, we measure fetal TSH, FT4, TT4, and TT3 in total blood cord at the delivery. Also, we measured the placental expression of Deiodinases by RT-PCR, western-blotting, and immunohistochemistry. The activity of Deiodinases was estimated quantified rT3 and T3 using T4 as a substrate. Mothers with GDM showed higher levels of TT3 during all pregnancy, and an increased in TSH during second and third trimester, while lower concentrations of neonatal TT4, FT4, and TT3; and an increased TSH level in umbilical cord blood from GDM. Placentae from GDM mothers have a higher expression and activity of Deiodinase 3, but lower Deiodinase 2, than NGT mothers. In conclusion, GDM favors high levels of TT3 during all gestation in the mother, low levels in TT4, FT4 and TT3 at the delivery in neonates, and increases deiodinase 3, but reduce deiodinase 2 expression and activity in the placenta.

Gestational Diabetes Mellitus (GDM) is a highly prevalent maternal pathology characterized by maternal glucose intolerance during pregnancy that is, associated with severe complications for both mother and offspring. Several risk factors have been related to GDM; one of the most important among them is genetic predisposition. Numerous single nucleotide polymorphisms (SNPs) in genes that act at different levels on various tissues, could cause changes in the expression levels and activity of proteins, which result in glucose and insulin metabolism dysfunction. In this review, we describe various SNPs; which according to literature, increase the risk of developing GDM. These SNPs include: (1) those associated with transcription factors that regulate insulin production and excretion, such as rs7903146 (TCF7L2) and rs5015480 (HHEX); (2) others that cause a decrease in protective hormones against insulin resistance such as rs2241766 (ADIPOQ) and rs6257 (SHBG); (3) SNPs that cause modifications in membrane proteins, generating dysfunction in insulin signaling or cell transport in the case of rs5443 (GNB3) and rs2237892 (KCNQ1); (4) those associated with enzymes such as rs225014 (DIO2) and rs9939609 (FTO) which cause an impaired metabolism, resulting in an insulin resistance state; and (5) other polymorphisms, those are associated with growth factors such as rs2146323 (VEGFA) and rs755622 (MIF) which could cause changes in the expression levels of these proteins, producing endothelial dysfunction and an increase of pro-inflammatory cytokines, characteristic on GDM. While the pathophysiological mechanism is unclear, this review describes various potential effects of these polymorphisms on the predisposition to develop GDM.

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Maternal thyroid alterations have been widely associated with the risk of gestational diabetes mellitus (GDM). This study aims to 1) test the first and the second trimester full maternal thyroid profile on the prediction of GDM, both alone and combined with non-thyroid data; and 2) make that prediction independent of the diagnostic criteria, by evaluating the effectiveness of the different maternal variables on the prediction of oral glucose tolerance test (OGTT) post load glycemia. Pregnant women were recruited in Concepción, Chile. GDM diagnosis was performed at 24–28 weeks of pregnancy by an OGTT (n = 54 for normal glucose tolerance, n = 12 for GDM). 75 maternal thyroid and non-thyroid parameters were recorded in the first and the second trimester of pregnancy. Various combinations of variables were assessed for GDM and post load glycemia prediction through different classification and regression machine learning techniques. The best predictive models were simplified by variable selection. Every model was subjected to leave-one-out cross-validation. Our results indicate that thyroid markers are useful for the prediction of GDM and post load glycemia, especially at the second trimester of pregnancy. Thus, they could be used as an alternative screening tool for GDM, independently of the diagnostic criteria used. The final classification models predict GDM with cross-validation areas under the receiver operating characteristic curve of 0.867 (p<0.001) and 0.920 (p<0.001) in the first and the second trimester of pregnancy, respectively. The final regression models predict post load glycemia with cross-validation Spearman r correlation coefficients of 0.259 (p = 0.036) and 0.457 (p<0.001) in the first and the second trimester of pregnancy, respectively. This investigation constitutes the first attempt to test the performance of the whole maternal thyroid profile on GDM and OGTT post load glycemia prediction. Future external validation studies are needed to confirm these findings in larger cohorts and different populations.