Effects and Mechanisms of n-3 Polyunsaturated Fatty Acids and Irisin on Maternal Abnormal Glucose Metabolism From Pregnancy to Postpartum

Gestational diabetes mellitus (GDM) is a well-established risk factor for the future development of type 2 diabetes in women. However, abnormal glucose metabolism is not exclusive to women with GDM; it can also occur during pregnancy and the postpartum period in those without a history of GDM. Recent studies have indicated that n-3 polyunsaturated fatty acids (n-3 PUFAs) can ameliorate insulin resistance and contribute to the prevention of type 2 diabetes in the general population. Concurrently, the novel myokine irisin has been shown to reduce insulin resistance and plays a significant regulatory role in human glucose metabolism. Ex vivo cellular studies further suggest that n-3 PUFAs can promote irisin expression. Based on this evidence, we hypothesize that n-3 PUFAs may improve postpartum glucose metabolism in women by upregulating irisin expression and subsequently activating the IRS-1/PI3K/AKT insulin signaling pathway. To test this hypothesis, a prospective cohort named Yuexiu Birth Cohort was established. The inclusion criteria were as follows: a) age 20-45 years; b) no pre-pregnancy history of diabetes, cardiovascular disease, thyroid disease, hematological disease, polycystic ovary syndrome, pregnancy-related infections, or psychiatric disorders; c) singleton pregnancy. This natural population cohort included both women with and without GDM. Follow-up data were collected at multiple time points: at 20-28 weeks of gestation (baseline: sociodemographic characteristics, lifestyle factors, anthropometric measurements, and fasting venous blood samples for assessment of glucose and lipid metabolism, erythrocyte membrane n-3 PUFA levels, and irisin levels); at 42 days postpartum (lifestyle and dietary habits, anthropometric measurements, fasting blood glucose and irisin levels); and during child follow-up at 6 months, 2 years, 3-4 years, and 5 years of age (evaluation of child growth, allergic diseases, and neuropsychological development, among other outcomes). The specific research objectives include: a) investigating the longitudinal trajectories of n-3 PUFAs and irisin from pregnancy to the postpartum period and their association with postpartum abnormal glucose metabolism (encompassing all postpartum women, not limited to those with a history of GDM); b) analyzing the correlation between n-3 PUFA and irisin levels; c) assessing the associations between maternal perinatal nutritional status (e.g., n-3 PUFA levels, dietary patterns, and other nutrients) and offspring health outcomes (including growth trajectories, neurodevelopment such as executive function and emotional/behavioral problems, and common diseases such as allergies). This study aims to systematically evaluate the perinatal nutritional status of pregnant women in Guangzhou, elucidate its associations with postpartum abnormal glucose metabolism and offspring health outcomes (growth, neuropsychological development, common diseases, etc.), and unravel the mechanistic link between n-3 PUFAs and irisin in the regulation of glucose metabolism in the general pregnant population. The findings are expected to provide a scientific basis for the prevention of postpartum type 2 diabetes and the promotion of early childhood health development.