Association and Predictive Value of Maternal Serum C1q/Tumor Necrosis Factor-related Protein-3 Ratio with Gestational Diabetes Mellitus in Early Pregnancy: a Prospective Study

doi:10.12114/j.issn.1007-9572.2021.02.130

Chinese General Practice ›› 2022, Vol. 25 ›› Issue (18): 2249-2254.DOI: 10.12114/j.issn.1007-9572.2021.02.130

Special Issue: 内分泌代谢性疾病最新文章合辑；肿瘤最新文章合辑；孕产妇健康研究最新文章合辑

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Association and Predictive Value of Maternal Serum C1q/Tumor Necrosis Factor-related Protein-3 Ratio with Gestational Diabetes Mellitus in Early Pregnancy: a Prospective Study

1. Department of Gynaecology, Tangshan Maternal and Child Health Hospital, Tangshan 063000, China
2. Department of Preventive Medicine, Chengde Medical University, Chengde 067000, China
3. Department of Obstetrics, Affiliated Hospital of Chengde Medical University, Chengde 067000, China
4. Institute of Basic Medicine, Chengde Medical University, Chengde 067000, China

Received:2021-09-10 Revised:2021-12-15 Published:2022-06-20 Online:2022-01-30
Contact: Shufang MAO
About author:
ZHANG L Q, GUO Y W, XU Q, et al. Association and predictive value of maternal serum C1q/tumor necrosis factor-related protein-3 ratio with gestational diabetes mellitus in early pregnancy: a prospective study[J]. Chinese General Practice, 2022, 25 (18) : 2249-2254.

妊娠早期血清补体C1q/肿瘤坏死因子相关蛋白3对妊娠期糖尿病的影响及预测价值：一项前瞻性研究

1.063000　河北省唐山市妇幼保健院妇科
2.067000　河北省承德市，承德医学院预防医学教研室
3.067000　河北省承德市，承德医学院附属医院产科
4.067000　河北省承德市，承德医学院基础医学研究所

通讯作者: 毛淑芳
作者简介:
张丽倩，郭艳巍，许倩，等.妊娠早期血清补体C1q/肿瘤坏死因子相关蛋白3对妊娠期糖尿病的影响及预测价值研究[J].中国全科医学，2022，25（18）：2249-2254. [www.chinagp.net] 作者贡献：张丽倩、毛淑芳提出研究思路，确定主要研究目标，负责研究设计并对研究监督管理，研究实施，前瞻性选取病例，收集并整理临床资料，撰写论文初稿；郭艳巍、毛淑芳进行研究质量控制及审校；张丽倩、杨珽参与病例资料收集；张丽倩、许倩负责研究的实施、评估、技术操作；毛淑芳确定论文终稿，对论文负责。
基金资助:
河北省科技计划项目(162777102D); 河北省医学科学研究重点课题计划(20170874); 2019年政府资助临床医学优秀人才培养项目补助计划

Abstract

Abstract:

Background

Gestational diabetes mellitus (GDM) is characterized by increased insulin resistance. As serum complement C1q/tumor necrosis factor-related protein 3 (CTRP3) ratio is closely related to insulin resistance, which may be involved in the development of GDM. However, the association and predictive value of serum CTRP3 ratio with GDM in early pregnancy have been rarely reported.

Objective

To explore the association and predictive value of serum CTRP3 ratio with GDM in early pregnancy, providing new ideas for the prevention and treatment of GDM.

Methods

Women in early pregnancy who underwent regular obstetric examinations in Obstetric Clinic, Affiliated Hospital of Chengde Medical University, were prospectively and consecutively enrolled from June 2018 to March 2019. Demographics, fasting plasma glucose (FPG) , fasting insulin (FINS) , glycosylated hemoglobin (HbA_1c) , triglyceride (TG) , total cholesterol (TC) , high-density lipoprotein cholesterol (HDL-C) , low-density lipoprotein cholesterol (LDL-C) and serum CTRP3 ratio measured at 6-14 weeks of gestation were collected. The 75 g oral glucose tolerance test (OGTT) was performed to screen GDM at 24-28 weeks of gestation. The patients were divided into GDM group and normal glucose tolerance (NGT) group.

Results

Finally, 368 of the 393 cases were enrolled for analysis, including 81 (22.0%) who were detected with GDM by the 75 g OGTT. Compared with those with normal glucose tolerance (NGT) diagnosed by the 75 g OGTT, GDM cases had much greater average age, pre-pregnancy BMI, FPG, FINS, HbA_1c, and TG (P<0.05) . Serum CTRP3 ratio in GDM group was lower than that in NGT group〔0.528 0 (0.461 3, 0.634 0) μg/L vs 0.604 8 (0.510 8, 0.666 0) μg/L, P=0.001〕. Multivariate Logistic regression analysis showed that serum CTRP3 ratio was an independently associated with GDM〔aOR=0.101, 95%CI (0.010, 0.997) , P≤0.05〕. The AUC of serum CTRP3 ratio in predicting GDM was 0.622〔95%CI (0.571, 0.672) 〕with 49.38% sensitivity, and 72.13% specificity when≤0.524 2 μg/L was chosen as the optimal cutoff value. The AUC of a combined prediction model (serum CTRP3 ratio in combination with age, pre-pregnancy BMI, FPG and HbA_1c) in predicting GDM was 0.841〔95%CI (0.799, 0.877) 〕, with 69.14% sensitivity and 89.20% specificity when 0.315 0 was chosen as the optimal cutoff value. The AUC of the combined prediction model was greater than that of serum CTRP3 ratio (Z=5.634, P<0.001) .

Conclusion

Increased serum CTRP3 ratio may be associated with lowered risk of GDM, so it could be used as an independent predictor for GDM in early pregnancy. Furthermore, its combined use with maternal demographic and metabolic indicators may produce a better predictive value for GDM in early pregnancy.

Key words: Diabetes, gestational, CTRP3, Body mass index, Glucose tolerance test

摘要：

背景

妊娠期糖尿病（GDM）以胰岛素抵抗为特征，补体C1q/肿瘤坏死因子相关蛋白3（CTRP3）与胰岛素抵抗关系密切，可能参与了GDM的发生、发展过程，但妊娠早期血清CTRP3与GDM的关系及其预测价值如何，相关研究报道较少。

目的

探讨妊娠早期血清CTRP3对GDM的影响及预测价值，为GDM的防治提供新思路。

方法

前瞻性连续选取2018年6月至2019年3月在承德医学院附属医院产科门诊正规产检的妊娠早期女性为研究对象。收集孕妇的一般资料，妊娠6~14周时检测空腹血糖（FPG）、空腹胰岛素（FINS）、糖化血红蛋白（HbA_1c）、三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）及血清CTRP3。妊娠24~28周时采用75 g口服葡萄糖耐量试验进行GDM筛查，分为GDM组和糖耐量正常（NGT）组。

结果

共纳入妊娠早期妇女393例，最终纳入分析368例，其中81例妊娠24~28周时诊断为GDM，GDM的发病率为22.0%。GDM组的年龄大于NGT组，妊娠前体质指数（BMI）、FPG、FINS、HbA_1c及TG均高于NGT组（P<0.05）。GDM组血清CTRP3低于NGT组〔0.528 0（0.461 3，0.634 0）μg/L与0.604 8（0.510 8，0.666 0）μg/L，P=0.001〕。多因素Logistic回归分析显示血清CTRP3是GDM发生的独立影响因素〔aOR=0.101，95%CI（0.010，0.997），P≤0.05〕。血清CTRP3预测GDM的截断值是0.524 2 μg/L，灵敏度为49.38%，特异度为72.13%，受试者工作特征曲线下面积（AUC）为0.622〔95%CI（0.571，0.672）〕；联合预测模型（CTRP3联合年龄、妊娠前BMI、FPG及HbA_1c）预测GDM的截断值是0.315 0，灵敏度为69.14%，特异度为89.20%，AUC为0.841〔95%CI（0.799，0.877）〕。联合预测模型预测GDM的AUC大于血清CTRP3的AUC（Z=5.634，P<0.001）。

结论

妊娠早期母体血清CTRP3升高可降低GDM的发生风险，是GDM的独立预测因子，与母体特征及代谢指标联合对GDM具有较好的预测价值。

关键词: 糖尿病，妊娠, 补体C1q/肿瘤坏死因子相关蛋白3, 体质指数, 葡糖耐量试验

Liqian ZHANG,Yanwei GUO,Qian XU, et al. Association and Predictive Value of Maternal Serum C1q/Tumor Necrosis Factor-related Protein-3 Ratio with Gestational Diabetes Mellitus in Early Pregnancy: a Prospective Study[J]. Chinese General Practice, 2022, 25(18): 2249-2254. DOI: 10.12114/j.issn.1007-9572.2021.02.130.
张丽倩,郭艳巍,许倩等. 妊娠早期血清补体C1q/肿瘤坏死因子相关蛋白3对妊娠期糖尿病的影响及预测价值：一项前瞻性研究[J]. 中国全科医学, 2022, 25(18): 2249-2254. DOI: 10.12114/j.issn.1007-9572.2021.02.130.

Figures/Tables 5

References 25

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组别	例数	年龄〔M（P₂₅，P₇₅），岁〕	民族〔n（%）〕				基线孕周〔M（P₂₅，P₇₅），周〕	妊娠前BMI 〔M（P₂₅，P₇₅），kg/m²〕
组别	例数	年龄〔M（P₂₅，P₇₅），岁〕	汉族	满族	回族	其他	基线孕周〔M（P₂₅，P₇₅），周〕	妊娠前BMI 〔M（P₂₅，P₇₅），kg/m²〕
GDM组	81	31.0（28.5，36.0）	50（61.7）	26（32.1）	3（3.7）	2（2.5）	12.4（12.1，13.1）	25.2（23.4，27.9）
NGT组	287	28.0（26.0，31.0）	167（58.2）	100（34.8）	4（1.4）	16（5.6）	12.4（12.0，12.9）	21.2（19.2，23.7）
Z（χ²）值		5.386	3.291^a				0.631	7.653
P值		<0.001	0.349				0.528	<0.001
组别	FPG〔M（P₂₅，P₇₅），mmol/L〕	FINS〔M（P₂₅，P₇₅），mU/L〕	HbA_1c〔M（P₂₅，P₇₅），%〕	TG〔M（P₂₅，P₇₅），mmol/L〕	TC〔M（P₂₅，P₇₅），mmol/L〕	HDL-C〔M（P₂₅，P₇₅），mmol/L〕	LDL-C〔M（P₂₅，P₇₅），mmol/L〕
GDM组	5.01（4.70，5.17）	11.82（8.27，17.67）	5.00（4.80，5.20）	1.57（1.13，2.03）	4.22（3.66，4.83）	1.57（1.33，1.71）	1.88（1.55，2.26）
NGT组	4.66（4.49，4.86）	8.06（6.13，11.41）	4.80（4.60，5.00）	1.22（1.00，1.65）	4.14（3.73，4.59）	1.58（1.38，1.82）	1.79（1.51，2.18）
Z（χ²）值	6.208	5.674	4.449	3.819	0.806	1.399	0.933
P值	<0.001	<0.001	<0.001	<0.001	0.420	0.162	0.351

组别	例数	年龄〔M（P₂₅，P₇₅），岁〕	民族〔n（%）〕				基线孕周〔M（P₂₅，P₇₅），周〕	妊娠前BMI 〔M（P₂₅，P₇₅），kg/m²〕
组别	例数	年龄〔M（P₂₅，P₇₅），岁〕	汉族	满族	回族	其他	基线孕周〔M（P₂₅，P₇₅），周〕	妊娠前BMI 〔M（P₂₅，P₇₅），kg/m²〕
GDM组	81	31.0（28.5，36.0）	50（61.7）	26（32.1）	3（3.7）	2（2.5）	12.4（12.1，13.1）	25.2（23.4，27.9）
NGT组	287	28.0（26.0，31.0）	167（58.2）	100（34.8）	4（1.4）	16（5.6）	12.4（12.0，12.9）	21.2（19.2，23.7）
Z（χ²）值		5.386	3.291^a				0.631	7.653
P值		<0.001	0.349				0.528	<0.001
组别	FPG〔M（P₂₅，P₇₅），mmol/L〕	FINS〔M（P₂₅，P₇₅），mU/L〕	HbA_1c〔M（P₂₅，P₇₅），%〕	TG〔M（P₂₅，P₇₅），mmol/L〕	TC〔M（P₂₅，P₇₅），mmol/L〕	HDL-C〔M（P₂₅，P₇₅），mmol/L〕	LDL-C〔M（P₂₅，P₇₅），mmol/L〕
GDM组	5.01（4.70，5.17）	11.82（8.27，17.67）	5.00（4.80，5.20）	1.57（1.13，2.03）	4.22（3.66，4.83）	1.57（1.33，1.71）	1.88（1.55，2.26）
NGT组	4.66（4.49，4.86）	8.06（6.13，11.41）	4.80（4.60，5.00）	1.22（1.00，1.65）	4.14（3.73，4.59）	1.58（1.38，1.82）	1.79（1.51，2.18）
Z（χ²）值	6.208	5.674	4.449	3.819	0.806	1.399	0.933
P值	<0.001	<0.001	<0.001	<0.001	0.420	0.162	0.351

CTRP3（μg/L）	例数	GDM
Q1（<0.496 3）	89	30（33.7）
Q2（0.496 3~）	94	21（22.3）
Q3（0.594 0~）	92	16（17.4）
Q4（0.661 8~）	93	14（15.1）
χ²值		10.865
P值		0.012

CTRP3（μg/L）	例数	GDM
Q1（<0.496 3）	89	30（33.7）
Q2（0.496 3~）	94	21（22.3）
Q3（0.594 0~）	92	16（17.4）
Q4（0.661 8~）	93	14（15.1）
χ²值		10.865
P值		0.012

变量	β	SE	Waldχ²值	P值	aOR（95%CI）
常量	-20.190	3.118	41.938	<0.001	—
年龄	0.135	0.035	14.561	<0.001	1.145（1.068，1.227）
妊娠前BMI	0.227	0.045	25.713	<0.001	1.296（1.195，1.406）
FPG	1.515	0.469	10.446	0.001	4.548（1.815，11.396）
HbA_1c	0.712	0.281	6.442	0.011	2.039（1.176，3.534）
CTRP3	-2.289	1.166	3.851	0.050	0.101（0.010，0.997）

Association and Predictive Value of Maternal Serum C1q/Tumor Necrosis Factor-related Protein-3 Ratio with Gestational Diabetes Mellitus in Early Pregnancy: a Prospective Study

妊娠早期血清补体C1q/肿瘤坏死因子相关蛋白3对妊娠期糖尿病的影响及预测价值：一项前瞻性研究

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指标	截断值	灵敏度（%）	特异度（%）	AUC	95%CI
CTRP3	0.524 2 μg/L	49.38	72.13	0.622	（0.571，0.672）
联合预测模型	0.315 0	69.14	89.20	0.841	（0.799，0.877）

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