Role of omega-3 polyunsaturated fatty acids in gestational diabetes, maternal and fetal insights: current use and future directions

Abstract

Abstract ω-3-Polyunsaturated fatty acids (ω-3 PUFAs) are widely used during pregnancy and gestational diabetes mellitus (GDM). ω-3 PUFAs are beneficial in the regulation of maternal and fetal metabolic function, inflammation, immunity, macrosomia (MAC), oxidative stress, preeclampsia, intrauterine growth, preterm birth, offspring metabolic function, and neurodevelopment. Dietary counseling is vital for improving therapeutic outcomes in patients with GDM. In maternal circulation, ω-3 PUFAs are transported via transporters, synthesis enzymes, and intracellular proteins, which activate nuclear receptors and play central roles in the cellular metabolic processes of placental trophoblasts. In patients with GDM, this process is compromised due to abnormal functioning of the placenta, which disrupts the normal mother to fetus transport. This results in reduced fetal levels of ω-3 PUFAs, which contributes negatively to fetal growth, metabolic function, and development. Dietary counseling and nutritional assessment remain challenging in the prevention and alleviation of GDM. Therefore, personalized approaches, including measurement of the ω-3 index, pharmacogenetic implementation strategies, and appropriate supplementation with ω-3 PUFAs are used to achieve sufficient distribution in the maternal and fetal fluids during the entire pregnancy period. Developing new dosing guidelines and personalized approaches, determining the mechanisms of ω-3 PUFAs in the placenta, and examining the pharmacodynamic and pharmacokinetics interactions involving ω-3 PUFAs will lead to better management and increase the quality of life of patients with GDM and their offspring. Moreover, different strategies for supplementing with ω-3 PUFAs, improving their placental transport, and pharmacological exploration of the maternal-fetal interactions will help to further elucidate the role of ω-3 PUFAs in women with GDM. In this review, we summarize the current information on the potential therapeutic benefits and clinical applicability of ω-3 PUFAs in patients with GDM and their offspring, highlighting recent progress and future perspectives in this field. Studies investigating the mechanisms of ω-3 PUFA transport to targeted tissues have spurred an interest in personalized treatment strategies for patients with GDM and their offspring. To implement such therapies, we need to clarify the index/ratio of ω-3 PUFAs in maternal and fetal fluids, delineate the ω-3 PUFA transport pathways, and establish the guidelines for FA profiling prepregnancy and during pregnancy-associated weight gain. Such therapies also need to take into account the gender of the fetus, and whether the patient is obese.