孕晚炎症因子未介导妊娠糖尿病与产后心血管代谢指标的关联

No role of the third-trimester inflammatory factors in the association of gestational diabetes mellitus with postpartum cardiometabolic indicators

孕晚炎症因子未介导妊娠糖尿病与产后心血管代谢指标的关联

Author：Xiayan Yu, Wenjing Qiang, Kexin Gong, Yidan Cao, Shuangqin Yan, Guopeng Gao, Fangbiao Tao, Beibei Zhu

Abstract

Background

The influence of gestational diabetes mellitus (GDM) on postpartum cardiometabolic indicators is primarily restricted to glucose and lipid metabolism, however the indicators for liver and kidney function have been rarely explored, and the role of the third-trimester inflammatory factors in these associations has never been investigated.

Methods

Based on the Ma’anshan birth cohort (MABC), women with or without GDM history were selected and invited to participate in a 6-year postpartum follow-up. The fasting blood samples were collected to measure 16 comprehensive metabolic indicators during a 6-year postpartum follow-up: fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), uric acid (UA), blood urea nitrogen (BUN), serum creatinine (SCR), etc. Seven inflammatory factors, including TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, and IL-17 A, were measured with serum samples collected during the third trimester of pregnancy. Linear regression models were used to analyze the associations between GDM and 6-year postpartum metabolic indicators, GDM and third-trimester inflammatory factors, and the third-trimester inflammatory factors and 6-year postpartum metabolic indicators. Mediating and moderating effect analyses were further performed to explore if the third-trimester inflammatory factors mediate or modify the association between GDM and postpartum cardiometabolic indicators.

Results

From July 2021 to August 2022, 307 participants have been followed up, with 99 women with a prior GDM history. Compared with those without GDM, individuals with a prior history of GDM had significantly elevated levels of FPG (β=0.40, 95% CI: 0.18 to 0.62, P_FDR < 0.001), HbA1c (β=0.22, 95% CI: 0.09 to 0.34, P_FDR = 0.009), TyG (β=0.22, 95% CI: 0.07 to 0.37, P_FDR = 0.024) at 6 years postpartum, and the association between GDM and SCR (β=2.43, 95% CI: 0.02 to 4.85, P_FDR = 0.144) reached nominal significance level. GDM history was associated with a decreased level ofthird-trimester IL-17 A (β = -0.58, 95% CI: -0.99 to -0.18, P_FDR = 0.035). No significant association between third-trimester inflammatory factors and 6-year postpartum metabolic indicators was observed. And no mediating or moderating

effect of third-trimester inflammatory factors was observed in those associations.

Conclusion

A prior history of GDM was significantly associated with elevated FPG, HbA1c, and TyG in women at 6 years postpartum, whereas third-trimester inflammatory factors had no role in mediating or moderating these associations.

Keywords

Gestational diabetes mellitus, Cardiometabolic indicators, Inflammatory factors, Cohort study

中文摘要

背景

妊娠期糖尿病（GDM）对产后心脏代谢指标的影响主要局限于葡萄糖和脂质代谢，但对肝脏和肾脏功能指标的影响却鲜有探讨，而孕晚期炎症因素在这些关联中的作用也从未被研究过。

方法

基于马鞍山优生优育队列（MABC），选取有或无 GDM 病史的妇女，邀请她们参加为期 6 年的产后随访。在为期6年的产后随访中，采集空腹血样测量16项综合代谢指标：空腹血浆葡萄糖（FPG）、糖化血红蛋白（HbA1c）、甘油三酯（TG）、总胆固醇（TC）、尿酸（UA）、血尿素氮（BUN）、血清肌酐（SCR）等。采集孕晚期的血清样本测定了七种炎症因子，包括 TNF-α、IFN-γ、IL-1β、IL-6、IL-10、IL-12p70 和 IL-17 A。线性回归模型用于分析 GDM 与产后 6 年代谢指标、GDM 与孕晚期炎症因子、孕晚期炎症因子与产后 6 年代谢指标之间的关系。进一步进行了中介效应和调节效应分析，以探讨孕晚期炎症因子是否会中介或改变 GDM 与产后心脏代谢指标之间的关联。

结果

从2021年7月到2022年8月，对307名参与者进行了随访，其中有99名妇女曾患GDM。与没有GDM病史的人相比，有GDM病史的人的 FPG（β=0.40，95% CI：0.18～0.62，P_FDR < 0.001）、HbA1c（β=0.22，95% CI：0.09～0.34，P_FDR = 0. GDM与SCR的相关性（β=2.43，95% CI：0.02～4.85，P_FDR=0.144）达到了名义显著性水平。GDM史与第三孕期IL-17 A水平下降有关（β=-0.58，95% CI：-0.99～-0.18，P_FDR=0.035）。未观察到第三孕期炎症因子与产后 6 年代谢指标之间存在明显关联。也没有发现第三孕期炎症因子对产后 6 年代谢指标有中介或调节作用。在这些关联中也没有观察到第三孕期炎症因素的中介或调节作用。

结论

曾患 GDM 的妇女与产后 6 年的 FPG、HbA1c 和 TyG 升高有显著相关性，而孕晚期的炎症因子对这些相关性没有介导或调节作用。

关键词

妊娠糖尿病、心脏代谢指标、炎症因子、队列研究