Placental expression of GLUT-1, GLUT-3, and GLUT-4 mRNA and transcriptome profiling in pregnant women with diabetes.

Abstract

Aims/introduction: Placental glucose transport is regulated by glucose transporter proteins (GLUTs). The study aimed to examine placental expression of GLUT-1, GLUT-3, and GLUT-4 mRNA in patients with type 1 diabetes, early gestational diabetes (eGDM), and healthy controls, and to investigate correlations between GLUTs expression and clinical parameters. Additionally, we compared placental transcriptome profiles in recruited subgroups.

Materials and methods: We recruited 59 pregnant women: 23 with type 1 diabetes, 17 with eGDM, and 19 controls. Patients with diabetes attended follow-up visits at each trimester. Transcriptome studies were performed in 4 patients per subgroup.

Results: The mean age was similar across all subgroups. eGDM patients had significantly higher BMI and were predominantly obese. We observed a significant 2-fold (P = 0.009) decrease in placental GLUT-3 mRNA expression in the type 1 diabetes and eGDM groups. GLUT-4 mRNA expression was significantly lower in the eGDM group compared to type 1 diabetes (3-fold) and controls (6-fold) (P = 0.007). There was a significant negative correlation between GLUT-3 (R = -0.29) and GLUT-4 (R = -0.27) mRNA expression and neonatal birth weight. GLUT-4 expression was negatively correlated with 1st trimester HbA1c (R = -0.72) and OGTT 120' (R = -0.82) results in eGDM patients, and 3rd trimester glycemic variability (R = -0.49) in type 1 diabetes. Microarray analysis revealed significant transcriptomic changes, with 45 down-regulated and 365 up-regulated genes in type 1 diabetes, and 21 significant changes in eGDM.

Conclusions: Placental samples from patients with diabetes exhibit changes in GLUTs expression, which correlates with neonatal growth and several glycemic parameters. Additionally, multiple changes in transcriptomic profiles are observed in hyperglycemic patients.