Gestational diabetes mellitus (GDM) is a form of glucose intolerance that develops during pregnancy, affecting approximately 14% of pregnancies worldwide. GDM leads to an excess supply of nutrients to the fetus, influencing fetal metabolism and potentially stimulating metabolic inflammation (metaflammation), which may impact liver function. In fact, increased fetal liver size has been reported in GDM pregnancies. This study investigated the impact of GDM on fetal metaflammation and its potential association with the liver function parameters γ-glutamyl transferase (GGT), alanine transaminase (ALT), and bilirubin, in umbilical cord plasma (UCP). UCP samples were collected following healthy (n=57) and GDM pregnancies (n=25). Gluco-metabolic and lipid profiles, inflammatory markers, and liver function parameters were analyzed and the impact of GDM and the interrelation of liver biomarkers with maternal and neonatal parameters was assessed. UCP from GDM pregnancies exhibited increased levels of metaflammation-associated markers, including triglycerides, interleukin-6 and C- reactive protein (CRP). Among liver parameters, the detoxification and antioxidant defense enzyme GGT was elevated, whereas ALT and bilirubin species remained unchanged. Correlation analysis revealed that although GGT was increased in GDM, it was associated with improved metabolic characteristics, including reduced insulin resistance, insulin, C-peptide, and leptin, and increased high-density lipoprotein. Overall, these findings indicate that GDM environment shifts fetal metabolism toward metaflammation and elevates GGT, an enzyme involved in detoxification and protection against oxidative stress. The inverse association of GGT with insulin resistance suggests a compensatory role of GGT, potentially mitigating fetal metabolic and inflammatory disturbances in GDM through its antioxidant activity.
Steiner et al. (Wed,) studied this question.