Overexpression of circRNAs LRP6 in gestational diabetes mellitus predicts foetal malformation and intrauterine death

Introduction: circRNA LRP6 participates in high-glucose-regulated cellular behaviours, while its role in gestational diabetes mellitus (GDM) is unclear. Our preliminary sequencing analysis revealed the altered expression of LRP6, suggesting its potential involvement in GDM and possible clinical value. This study explored the involvement of LRP6 in GDM.

Methods: In this study, a total of 300 pregnant women were enrolled and followed up until delivery. The occurrence of GDM and adverse outcomes was recorded. These 300 participants were grouped into high and low LRP6 level groups (n=150; cutoff=median). Occurrence of GDM and adverse outcomes were compared between the two groups. ROC curve analysis was conducted to explore the role of LRP6 expression on the day of admission in predicting GDM. Associations between LRP6 expression and adverse outcomes were analysed with the Chi-squared test.

Results: We observed that participants in the high LRP6 level group experienced a higher incidence of GDM during follow-up (33/150) compared to those in the low LRP6 level group (10/150). Compared to participants who developed GDM during follow-up, participants who did not develop GDM showed lower expression levels of LRP6 in plasma. ROC curve analysis showed that high expression levels of LRP6 on the day of admission effectively distinguished potential GDM patients from other participants. Interestingly, LRP6 was only closely associated with foetal malformation and intrauterine death, but not premature delivery, hypertension, macrosomia, intrauterine distress, miscarriage and intrauterine infection in all participants.

Conclusion: Therefore, increased expression levels of LRP6 in GDM predicts foetal malformation and intrauterine death.