基于出生队列的孕期维生素D缺乏－代谢性炎症在母婴糖稳态受损中的作用及干预研究

代谢性炎症是糖稳态受损的核心机制。前期研究发现VD缺乏与母胎炎症及GDM风险关联，推论VD缺乏通过驱动代谢性炎症增加母婴糖稳态受损易感性。基于已建出生队列，应用代谢组学技术小样本筛选与糖稳态相关炎症因子（TNF-α等）高度关联的孕外周特异脂代谢物，分析代谢通路。再大样本验证25(OH)D－特异脂代谢物－炎症因子间关系，探讨孕期VD缺乏是否通过特异脂代谢通路促进母胎炎症。进行孕期、出生时、产后第４年母子糖代谢评价，正交设计（VD－炎症）探讨VD缺乏是否增加母子糖稳态受损易感性。新建孕期干预队列，对VD缺乏孕妇补充VD3，孕24周后行OGTT并保存外周血。检测干预前后炎症因子和特异脂代谢物。分娩后收集脐血和胎盘，检测炎症因子、C肽和HbA1c。探讨孕期补充VD是否抑制代谢性炎症、降低母胎糖稳态受损易感性。本研究将从疾病易感性视角，阐明VD作为代谢性炎症的可控性调节因素在保护母婴糖稳态中的价值。

Metaflammation has been widely regarded as the major mechanism underlying impaired glucose homeostasis. Our previous studies have found that vitamin D (VD) deficiency is associated with increased maternal and fetal inflammation and risk of gestational diabetes mellitus (GDM). Thus, we hypothesize that prenatal VD deficiency increases the susceptibility of impaired maternal and infant glucose homeostasis by driving metaflammation. Based on the established birth cohort, specific lipid metabolites associated with glucose homeostasis related inflammatory cytokines (TNF-α, etc) will be screened by using metabolomics technique among small sample and the metabolic pathway will be analyzed as well. Then, a large sample analysis will be conducted to confirm the relationships between prenatal 25(OH)D- specific lipid metabolites - inflammatory cytokines, and to explore whether prenatal VD deficiency promotes inflammatory response through specific lipid metabolism pathway. The glucose metabolic function of mother-infant pairs will be evaluated during pregnancy, delivery and the fourth year postpartum. Using orthogonal design (VD－inflammation ), we will assess whether prenatal VD deficiency increases the susceptibility of impaired maternal and infant glucose homeostasis. We will establish a new birth cohort. Pregnant women with VD deficiency will receive vitamin D3 supplementation from 8-16 gestational weeks to 32 gestational weeks. Oral glucose tolerance test will be conducted and peripheral blood sample will be collected. Inflammatory cytokines and specific lipid metabolites in blood sample before and after intervention will be detected. After delivery, cord blood and placenta will be collected to detect inflammatory cytokines, C peptide and HbA1c. We will evaluate whether prenatal VD supplementation inhibits metaflammation and reduces susceptibility of impaired maternal and fetal glucose homeostasis. From the perspective of disease susceptibility, this study will clarify the value of VD as a controllable regulatory factor of metaflammation in the protection of maternal and infant glucose homeostasis.