妊娠糖尿病患者NLRP3、CTRP6和IL-1β检测的临床意义

doi:10.3969/j.issn.1673-8640.2023.10.006

摘要/Abstract

摘要：

目的探讨血清NOD样受体蛋白3（NLRP3）、C1q/肿瘤坏死因子相关蛋白6（CTRP6）、白细胞介素1β（IL-1β）在妊娠糖尿病（GDM）中的变化，及其判断不良妊娠结局的价值。方法选取2018年1月—2020年12月南通市妇幼保健院GDM患者145例（GDM组），以正常妊娠女性145例作为对照组。检测所有研究对象NLRP3、CTRP6、IL-1β、空腹胰岛素（FINS）、糖化血红蛋白（HbA_1c）、空腹血糖（FPG），计算胰岛β细胞功能指数（HOMA-β）、胰岛素抵抗指数（HOMA-IR）。根据GDM患者妊娠结局分为不良妊娠组和正常妊娠组。采用Pearson相关分析评估GDM组各项指标之间的相关性。采用受试者工作特征（ROC）曲线评价各项指标判断不良妊娠结局的效能。结果与对照组比较，GDM组CTRP6、NLRP3、IL-1β、FINS、HbA_1c、FPG、HOMA-IR显著升高（P<0.05），HOMA-β显著降低（P<0.05）。 Pearson相关分析结果显示，CTRP6、NLRP3、IL-1β与FINS、HbA_1c、FPG、HOMA-IR呈正相关（P<0.05），与HOMA-β呈负相关（P<0.05）。与正常妊娠组比较，不良妊娠组CTRP6、NLRP3、IL-1β、FINS、HbA_1c、FPG、HOMA-IR显著升高（P<0.05），HOMA-β显著降低（P<0.05）。ROC曲线分析结果显示，FINS、HbA_1c、FPG、HOMA-β、HOMA-IR判断不良妊娠结局的曲线下面积（AUC）均<0.7，CTRP6、NLRP3和IL-1β判断不良妊娠结局的AUC分别为0.846、0.802、0.871，三者联合检测的AUC为0.931。结论 GDM患者CTRP6、NLRP3、IL-1β水平升高，且与胰岛素抵抗和血糖水平密切相关。CTRP6、NLRP3、IL-1β联合检测在判断不良妊娠结局中有较高的临床价值。

关键词: NOD样受体蛋白, C1q/肿瘤坏死因子相关蛋白 6, 白细胞介素1β, 妊娠糖尿病

Abstract:

Objective To investigate the clinical significance of serum NOD-like receptor protein（NLRP3），C1q/tumor necrosis factor-related protein 6（CTRP6） and interleukin 1 beta（IL-1β） in patients with gestational diabetes mellitus（GDM）. Methods Totally，145 patients with GDM in Nantong Maternal and Child Health Care Hospital from January 2018 to December 2020 were enrolled as GDM group，and 145 healthy pregnant women were enrolled as control group. Serum NLRP3，CTRP6，IL-1β levels and fasting insulin（FINS），glycated hemoglobin A_1c（HbA_1c），fasting plasma glucose（FPG），homa-beta cell function index（HOMA-β），homeostasis model assessment of insulin resistance（HOMA-IR） levels were determined. According to the pregnancy outcomes，they were classified into adverse pregnancy outcome group and normal pregnancy outcome group. Pearson correlation analysis was used to evaluate the correlation between various indicators in GDM group. Receiver operating characteristic（ROC） curve was used to evaluate the effectiveness of all the indicators in determining adverse pregnancy outcomes. Results Compared with control group，CTRP6，NLRP3，IL-1β，FINS，HbA_1c，FPG and HOMA-IR levels in GDM group were increased（P<0.05），while HOMA-β was decreased（P<0.05）. CTRP6，NLRP3 and IL-1β were positively correlated with FINS，HbA_1c，FPG and HOMA-IR（P<0.05），and they were negatively correlated with HOMA-β levels（P<0.05）. Compared with normal pregnancy group，CTRP6，NLRP3，IL-1β，FINS，HbA_1c，FPG and HOMA-IR were increased in adverse pregnancy group（P<0.05），while HOMA-β was decreased（P<0.05）. The areas under curves（AUC） of FINS，HbA_1c，FPG，HOMA-β and HOMA-IR for judging adverse pregnancy outcome were all <0.7，while the AUC of CTRP6，NLRP3 and IL-1β for judging adverse pregnancy outcome were 0.846，0.802 and 0.871，respectively. The AUC of combined determination was 0.931. Conclusions The serum levels of CTRP6，NLRP3 and IL-1β in patients with GDM are increased，and they are closely related to insulin resistance and blood glucose levels. The combined determination of CTRP6，NLRP3 and IL-1β has high clinical value in predicting adverse pregnancy outcome.

Key words: NOD-like receptor protein, C1q/tumor necrosis factor-related protein 6, Interleukin 1 beta, Gestational diabetes mellitus

中图分类号:

R446.1

钱琳玉, 梁卫芳, 唐思晨. 妊娠糖尿病患者NLRP3、CTRP6和IL-1β检测的临床意义[J]. 检验医学, 2023, 38(10): 936-940.

QIAN Linyu, LIANG Weifang, TANG Sichen. Determination and clinical significance of NLRP3，CTRP6 and IL-1β in patients with gestational diabetes mellitus[J]. Laboratory Medicine, 2023, 38(10): 936-940.

图/表 6

参考文献 16

[1]	张淳义, 倪颖华, 季鑫, 等. 妊娠期糖尿病患者糖化血红蛋白和糖化白蛋白水平与新生儿体重的相关性[J]. 检验医学, 2017, 32(3):165-168.
[2]	ZHUANG Y, ZHANG J, LI Y, et al. B lymphocytes are predictors of insulin resistance in women with gestational diabetes mellitus[J]. Endocr Metab Immune Disord Drug Targets, 2019, 19(3):358-366. DOI PMID
[3]	BRAGA F O, NEGRATO C A, MATTA M F B D, et al. Relationship between inflammatory markers,glycated hemoglobin and placental weight on fetal outcomes in women with gestational diabetes[J]. Arch Endocrinol Metab, 2019, 63(1):22-29. DOI URL
[4]	ZHUO X, TIAN Y, WEI Y, et al. Flavone of Hippophae(H-flavone) lowers atherosclerotic risk factors via upregulation of the adipokine C1q/tumor necrosis factor-related protein 6(CTRP6) in macrophages[J]. Biosci Biotechnol Biochem, 2019, 83(11):2000-2007. DOI URL
[5]	WANG M, TANG X, LI L, et al. C1q/TNF-related protein-6 is associated with insulin resistance and the development of diabetes in Chinese population[J]. Acta Diabetol, 2018, 55(12):1221-1229. DOI PMID
[6]	GAO L, LU G, LU Y, et al. Diabetes aggravates acute pancreatitis possibly via activation of NLRP3 inflammasome in db/db mice[J]. Am J Transl Res, 2018, 10(7):2015-2025. DOI PMID
[7]	中华医学会妇产科学分会产科学组, 中华医学会围产医学分会妊娠合并糖尿病协作组. 妊娠合并糖尿病诊治指南(2014)[J]. 中华妇产科杂志, 2014, 49(8):561-569.
[8]	崔倩卫, 冷吉燕, 卜丽梅, 等. 高血压伴胰岛素抵抗患者血清脂联素水平与动脉粥样硬化的相关性研究[J]. 中国老年学杂志, 2011, 31(11):1959-1961.
[9]	MCLNTYRE H D, CATALANO P, ZHANG C, et al. Gestational diabetes mellitus[J]. Nat Rev Dis Primers, 2019, 5:47. DOI PMID
[10]	ZHENG W, ZHANG S, MA H, et al. C1qTNF-related protein-6 protects against doxorubicin-induced cardiac injury[J]. J Cell Biochem, 2019, 120(6):10748-10755. DOI URL
[11]	WU W, ZHANG J, ZHAO C, et al. Lentivirus-mediated CTRP6 silencing ameliorates diet-induced obesity in mice[J]. Exp Cell Res, 2018, 367(1):15-23. DOI PMID
[12]	LACROIX M, LIZOTTE F, HIVERT M F, et al. Calcifediol decreases interleukin-6 secretion by cultured human trophoblasts from GDM pregnancies[J]. J Endocr Soc, 2019, 3(11):2165-2178. DOI PMID
[13]	DING T, WANG S, ZHANG X, et al. Kidney protection effects of dihydroquercetin on diabetic nephropathy through suppressing ROS and NLRP3 inflammasome[J]. Phytomedicine, 2018, 41:45-53. DOI PMID
[14]	LEGRAND-POELS S, ESSER N, L'HOMME L, et al. Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes[J]. Biochem Pharmacol, 2014, 92(1):131-141.
[15]	夏红飞, 郝艳红, 彭景楩. 妊娠大鼠子宫和胎盘IL-1β表达及IFN-γ对其表达的影响[J]. 动物学报, 2004, 50(1):48-54.
[16]	赵璐, 杨华, 刘国艳. NLR家族Pyrin域蛋白3炎症小体与妊娠的研究进展[J]. 国际妇产科学杂志, 2021, 48(3):255-258.

组别	例数	年龄/岁	孕周/周	孕次/次	BMI/ （kg/m²）	TG/ （mmol/L）	TC/ （mmol/L）	LDL-C/ （mmol/L）	HDL-C/ （mmol/L）
GDM组	145	28.7±4.9	27.9±1.7	1.74±0.56	26.17±1.94	2.51±0.39	4.61±0.74	2.46±0.29	1.43±0.28
对照组	145	28.1±4.2	27.6±1.3	1.68±0.52	25.94±1.87	2.60±0.42	4.49±0.78	2.51±0.32	1.36±0.38
t值		1.121	1.688	0.945	1.028	1.891	1.344	1.394	1.786
P值		0.264	0.093	0.345	0.305	0.060	0.180	0.164	0.075

组别	例数	年龄/岁	孕周/周	孕次/次	BMI/ （kg/m²）	TG/ （mmol/L）	TC/ （mmol/L）	LDL-C/ （mmol/L）	HDL-C/ （mmol/L）
GDM组	145	28.7±4.9	27.9±1.7	1.74±0.56	26.17±1.94	2.51±0.39	4.61±0.74	2.46±0.29	1.43±0.28
对照组	145	28.1±4.2	27.6±1.3	1.68±0.52	25.94±1.87	2.60±0.42	4.49±0.78	2.51±0.32	1.36±0.38
t值		1.121	1.688	0.945	1.028	1.891	1.344	1.394	1.786
P值		0.264	0.093	0.345	0.305	0.060	0.180	0.164	0.075

组别	例数	CTRP6/ （μg/L）	NLRP3/ （pg/mL）	IL-1β/ （pg/mL）	FINS/（mU/L）	HbA_1c/%	FPG/（mmol/L）	HOMA-β	HOMA-IR
GDM组	145	506.43±119.52	236.80±57.14	27.21±6.74	10.59±1.42	6.28±0.61	5.49±0.31	35.98±9.39	4.34±0.61
对照组	145	391.76±101.98	156.20±32.12	17.69±4.24	7.31±1.54	4.63±0.69	4.47±0.22	61.08±12.15	1.98±0.54
t值		8.789	14.817	14.397	18.855	21.573	32.311	19.683	34.883
P值		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

组别	例数	CTRP6/ （μg/L）	NLRP3/ （pg/mL）	IL-1β/ （pg/mL）	FINS/（mU/L）	HbA_1c/%	FPG/（mmol/L）	HOMA-β	HOMA-IR
GDM组	145	506.43±119.52	236.80±57.14	27.21±6.74	10.59±1.42	6.28±0.61	5.49±0.31	35.98±9.39	4.34±0.61
对照组	145	391.76±101.98	156.20±32.12	17.69±4.24	7.31±1.54	4.63±0.69	4.47±0.22	61.08±12.15	1.98±0.54
t值		8.789	14.817	14.397	18.855	21.573	32.311	19.683	34.883
P值		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

项目	FINS	HbA_1c	FPG	HOMA-β	HOMA-IR
CTRP6
r值	0.391	0.334	0.429	-0.226	0.338
P值	<0.001	<0.001	<0.001	0.014	<0.001
NLRP3
r值	0.335	0.317	0.372	-0.354	0.228
P值	<0.001	<0.001	<0.001	<0.001	0.012
IL-1β
r值	0.394	0.422	0.347	-0.359	0.325
P值	0.022	0.018	0.009	<0.001	<0.001