妊娠期糖尿病患者不同孕期纤维蛋白单体水平变化及与糖化血红蛋白变异性的关系

Changes in fibrin monomer level and it's relationship with glycosylated hemoglobin variability in gestational diabetes mellitus

摘要

目的 探究妊娠期糖尿病(GDM)患者不同孕期纤维蛋白单体(FM)水平变化及与糖化血红蛋白变异系数(HbA_1c-CV)的关系。方法 选择2022年1月至2023年2月衡水市妇幼保健院产科收治的137例GDM孕妇作为GDM组,另选择同期同院建档并接受产检的140例健康孕妇作为非GDM组,收集患者的FM、HbA_1c-CV等临床资料.多因素Logistic回归分析影响GDM发生的危险因素;应用限制性立方样条法估计FM、HbA_1c-CV水平和GDM的剂量-反应关系;利用多元线性回归分析FM与HbA_1c-CV的相关性;采用bootstrap方法分析FM是否介导了HbA_1c-CV和GDM之间的关联。结果 多因素Logistic回归分析结果显示有糖尿病家族史、C反应蛋白(CRP)≥8 mg/L、D-二聚体(D-D)≥1.20 μg/mL、空腹血糖(FPG)≥6.10 mmol/L、糖化血红蛋白(HbA_1c)≥6.00%、平均糖化血红蛋白(MHbA_1c)≥6.00%、糖化血红蛋白标准差(HbA_1c-SD)≥1.80%、HbA_1c-CV≥0.60%、FM≥3.60 μg/mL均为影响GDM发生的危险因素(OR值介于1.459~5.678之间,P<0.05);在孕早期、孕中期及孕晚期,GDM组FM、FPG、HbA_1c、MHbA_1c、HbA_1c-SD、HbA_1c-CV水平均高于非GDM组,差异有统计学意义(t值介于3.763~37.141之间,P<0.05);剂量-反应关系分析显示,不同孕期FM、HbA_1c-CV表达水平和GDM呈非线性反应关系(非线性检验P<0.001);多元线性回归分析显示,未校正模型、调整模型1、调整模型2结果均显示,FM是影响GDM患者HbA_1c-CV水平的危险因素(β值分别为1.683、1.879、2.015,P<0.05);将FM转化为二分类变量与五分类变量后,结果表明FM水平与HbA_1c-CV之间仍存在独立正相关性(β值介于1.691~3.686之间,P<0.001);中介效应分析结果表明,HbA_1c-CV对GDM发生风险具有直接影响(β=0.159,95%CI:0.112~0.227),且FM部分介导了HbA_1c-CV对GDM发生风险的影响(β=0.185,95%CI:0.152~0.236),总效应值β′=0.328,中介效应占总效应的56.74%(P<0.05)。结论 在不同孕期妊娠期糖尿病组的FM、HbA_1c-CV均显著高于非妊娠期糖尿病组.FM是预测妊娠期糖尿病患者HbA_1c-CV升高的重要影响因素.HbA_1c-CV对妊娠期糖尿病发生风险具有直接影响,且FM部分介导了HbA_1c-CV对妊娠期糖尿病发生风险的影响.

Abstract

Objective To investigate relationship between fibrin monomer (FM) level and glycosylated hemoglobin (HbA_1c) coefficient of variation (HbA_1c-CV) in patients with gestational diabetes mellitus (GDM) in three trimesters of pregnancy. Methods A total of 137 GDM pregnant women who admitted to Department of Obstetrics, Hengshui Municipal Maternal and Child Health Hospital from January 2022 to February 2023 were selected as GDM group, and 140 healthy pregnant women who received prenatal examination in the same hospital were selected as non-GDM group. FM, HbA_1c-CV and other clinical data of the patients were collected. Multivariate Logistic regression was used to analyze risk factors of GDM. Restricted cubic spline method was used to estimate dose-response relationships of FM and HbA_1c-CV with GDM. Multiple linear regression was used to analyze correlation between FM and HbA_1c-CV. Bootstrap method was used to analyze whether FM mediated the association between HbA_1c-CV and GDM. Results Multivariate Logistic regression analysis showed that family history of diabetes mellitus, C-reactive protein (CRP) ≥ 8 mg/L, D-dimer (D-D) ≥ 1.20 μg/mL, fasting plasma glucose (FPG) ≥ 6.10 mmol/L, HbA_1c ≥ 6.00%, mean hemoglobin A_1c (MHbA_1c) ≥ 6.00%, glycosylated hemoglobin standard deviation (HbA_1c-SD) ≥ 1.80%, HbA_1c-CV ≥ 0.60% and FM ≥ 3.60 μg/mL were all risk factors for GDM (OR = 1.459-5.678, all P < 0.05). In the first trimester, the second trimester and the third trimester of pregnancy, the levels of FM, FPG, HbA _1c, MHbA_1c, HbA_1c-SD and HbA_1c-CV in the GDM group were higher than those in the non-GDM group, and the differences were statistically significant (t = 3.763-37.141, all P < 0.05). The dose-response relationship analysis showed that FM, HbA _1c-CV levels in different trimesters of pregnancy had non-linear response relationships with GDM (non-linear test, both P < 0.001). Multiple linear regression analysis showed that FM was a risk factor affecting HbA _1c-CV level in GDM patients in the uncorrected model, the corrected model I and the corrected model II (β = 1.683, 1.879 and 2.015 respectively, all P < 0.05). When FM was converted to two-category variable and five-category variable, there were still independent positive correlations between FM levels and HbA _1c-CVs levels (β = 1.691-3.686, all P < 0.001). The mediating effect analysis showed that HbA _1c-CV had a direct effect on the risk of GDM (β = 0.159, 95% CI: 0.112-0.227), and FM partially mediated the effect of HbA_1c-CV on the risk of GDM (β = 0.185, 95% CI: 0.152-0.236), the total effect value β′ = 0.328, and the mediating effect accounted for 56.74% of the total effect (all P < 0.05). Conclusion FM and HbA _1c-CV levels of the pregnant women in the GDM group are significantly higher than those in the non-GDM group in all three trimesters of pregnancy. FM is an important factor for predicting elevation of HbA_1c-CV level in GDM patients. HbA_1c-CV has a direct effect on the risk of GDM, and FM partially mediates the effect of HbA_1c-CV on the risk of GDM.

关键词

妊娠期糖尿病 / 不同孕期 / 纤维蛋白单体 / 糖化血红蛋白变异性

Key words

gestational diabetes mellitus / three trimesters of pregnancy / fibrin monomer / glycosylated hemoglobin variability

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