孕早期全身炎症水平与妊娠期糖尿病发病风险的关联研究*

doi:10.3870/j.issn.1672-0741.25.10.033

摘要/Abstract

摘要： 目的探讨孕早期全身免疫炎症指数(systemic immune-inflammation index,SII)和全身炎症反应指数(systemic inflammation response index,SIRI)对妊娠期糖尿病(gestational diabetes mellitus,GDM)、GDM亚型及血糖水平的影响。方法采用回顾性队列研究,从广东省妇幼保健院2015~2024年电子病历系统中抽取34171名孕妇作为研究对象。GDM及其亚型采用75 g口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)诊断。利用修正泊松回归模型、多分类Logistic回归模型及线性回归模型分析SII、SIRI与GDM、GDM亚型及血糖水平的关联,运用限制性立方样条模型探讨SII、SIRI与GDM及血糖水平可能的非线性关系。结果调整协变量后,修正泊松回归模型结果显示自然对数转换的SII(RR=1.30,95%CI:1.23~1.37)和SIRI(RR=1.21,95%CI:1.16~1.27)升高与GDM发病风险增加相关。多分类Logistic回归模型结果显示自然对数转换的SII、SIRI升高与GDM中单纯负荷后高血糖亚型(SII: OR=1.36,95% CI: 1.26~1.47; SIRI: OR=1.27,95% CI:1.19~1.36)及混合高血糖亚型(SII:OR=1.82,95% CI: 1.49~2.21; SIRI:OR=1.47,95% CI: 1.25~1.73)发病风险增加相关,对单纯空腹高血糖亚型(SII: OR=1.22,95% CI: 0.99~1.51; SIRI:OR=1.09,95% CI: 0.92~1.30)发病风险的影响无统计学意义。限制性立方样条结果显示自然对数转换的SII与空腹血糖、负荷后1 h血糖水平呈J型剂量反应关系,与负荷后2 h血糖水平呈线性剂量反应关系;自然对数转换的SIRI与负荷后1、2 h血糖水平呈线性剂量反应关系。结论孕早期SII、SIRI升高与GDM以及其单纯负荷后高血糖亚型和混合高血糖亚型发病风险增加显著相关,研究结果可为GDM的早期风险识别与亚型针对性管理提供新的炎症标志物。

关键词: 全身免疫炎症指数, 全身炎症反应指数, 孕早期, 妊娠期糖尿病, 血糖水平

Abstract: Objective To evaluate the impact of the first-trimester systemic immune-inflammation index(SII)and systemic inflammation response index(SIRI)on gestational diabetes mellitus(GDM),subtypes of GDM,and blood glucose levels. Methods A retrospective cohort study was conducted,involving 34,171 pregnant women from the electronic medical record system of Guangdong Women and Children Hospital from 2015 to 2024.GDM patients and their subtypes were diagnosed via the 75 g oral glucose tolerance test.A modified Poisson regression model,multinomial Logistic regression model and linear regression model were used to explore the associations of the SII and SIRI with GDM,subtypes of GDM and blood glucose levels,respectively.A restricted cubic spline(RCS)model was applied to explore the possible nonlinear relationships between SII,SIRI and GDM as well as blood glucose levels. Results After adjusting for covariates,a modified Poisson regression model revealed that an elevated ln-transformed SII(RR=1.30,95%CI:1.23-1.37)and SIRI(RR=1.21,95%CI:1.16-1.27)were associated with an increased risk of developing GDM.The multinomial logistic regression model revealed that elevated ln-transformed SII and SIRI were associated with an increased risk of developing GDM-isolated post-load hyperglycemia(GDM-IPH)(SII:OR=1.36,95%CI:1.26-1.47;SIRI:OR=1.27,95%CI:1.19-1.36)and GDM-combined hyperglycemia(GDM-CH)(SII:OR = 1.82,95%CI:1.49-2.21;SIRI:OR = 1.47,95%CI:1.25-1.73),but elevated SII and SIRI did not have statistically significant effect on the risk of developing GDM-isolated fasting hyperglycemia(GDM-IFH)(SII:OR=1.22,95%CI:0.99-1.51;SIRI:OR=1.09,95%CI:0.92-1.30).The RCS results revealed that the ln-transformed SII exhibited a J-shaped dose-response relationship with fasting and 1-hour blood glucose levels and a linear dose-response relationship with 2-hour blood glucose levels,whereas the ln-transformed SIRI exhibited a linear dose-response relationship with 1- and 2-hour blood glucose levels. Conclusion Elevated SII and SIRI in the first trimester are significantly associated with an increased risk of GDM and its GDM-IPH and GDM-CH subtypes.The results provide new inflammatory markers for early risk identification and subtype-specific management of GDM.

Key words: systemic immune-inflammation index, systemic inflammation response index, first trimester, gestational diabetes mellitus, blood glucose level

中图分类号:

R587.1

刘炳海, 郭雯雯, 颜莲妍, 彭静, 武丽, 王友洁, 张丽. 孕早期全身炎症水平与妊娠期糖尿病发病风险的关联研究^*[J]. 华中科技大学学报（医学版）, 2026, 55(1): 53-60.

Liu Binghai, Guo Wenwen, Yan Lianyan et al. Association between Systemic Inflammation in the First Trimester and the Risk of Gestational Diabetes Mellitus[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(1): 53-60.

参考文献

[1] International Association of Diabetes and Pregnancy Study Groups Consensus Panel,Metzger B E,Gabbe S G,et al.International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy[J].Diabetes Care,2010,33(3):676-682.
[2] Moon J H,Jang H C.Gestational diabetes mellitus:diagnostic approaches and maternal-offspring complications[J].Diabetes Metab J,2022,46(1):3-14.
[3] Sweeting A,Wong J,Murphy H R,et al.A clinical update on gestational diabetes mellitus[J].Endocr Rev,2022,43(5):763-793.
[4] Gao C,Sun X,Lu L,et al.Prevalence of gestational diabetes mellitus in mainland China:a systematic review and meta-analysis[J].J Diabetes Investig,2019,10(1):154-162.
[5] Venkatesh K K,Lynch C D,Powe C E,et al.Risk of adverse pregnancy outcomes among pregnant individuals with gestational diabetes by race and ethnicity in the united states,2014-2020[J].JAMA,2022,327(14):1356-1367.
[6] Harrison J,Melov S,Kirby A C,et al.Pregnancy outcomes in women with gestational diabetes mellitus by models of care:A retrospective cohort study[J].BMJ Open,2022,12(9):e065063.
[7] Sweeting A,Hannah W,Backman H,et al.Epidemiology and management of gestational diabetes[J].Lancet,2024,404(10448):175-192.
[8] Vounzoulaki E,Khunti K,Abner S C,et al.Progression to ty-pe 2 diabetes in women with a known history of gestational diabetes:systematic review and meta-analysis[J].BMJ,2020,369:m1361.
[9] Kim C.Management of cardiovascular risk in perimenopausal women with diabetes[J].Diabetes Metab J,2021,45(4):492-501.
[10] Holmes C.Review:Systemic inflammation and Alzheimer’s di-sease[J].Neuropathol Appl Neurobiol,2013,39(1):51-68.
[11] 赵侃侃,郑永权.通过Luminex检测不同性别儿童肥胖与全身炎症水平的相关性[J].中国妇幼保健,2025,40(8):1424-1428.
Zhao K K,Zheng Y Q.Correlation between obesity and systemic inflammation in children of different genders detected by Luminex[J].Matern Child Health Care China,2025,40(8):1424-1428.
[12] 欧武英,李闻文,叶芳丽.妊娠糖尿病患者白细胞介素6、肿瘤坏死因子α及脂联素水平及其相关性研究[J].中国现代医学杂志,2016,26(2):64-67.
Ou W Y,Li W W,Ye F L.Levels of interleukin 6,tumor necrosis factor α and adiponectin and their correlation in patients with gestational diabetes mellitus[J].Chin J Mod Med,2016,26(2):64-67.
[13] Hu B,Yang X R,Xu Y,et al.Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma[J].Clin Cancer Res,2014,20(23):6212-6222.
[14] Qi Q,Zhuang L,Shen Y,et al.A novel systemic inflammation response index(SIRI)for predicting the survival of patients with pancreatic cancer after chemotherapy[J].Cancer,2016,122(14):2158-2167.
[15] Xu M,Chen R,Liu L,et al.Systemic immune-inflammation index and incident cardiovascular diseases among middle-aged and elderly Chinese adults:The dongfeng-tongji cohort study[J].Atherosclerosis,2021,323:20-29.
[16] Nicoară D M,Munteanu A I,Scutca A C,et al.Assessing the relationship between systemic immune-inflammation index and metabolic syndrome in children with obesity[J].Int J Mol Sci,2023,24(9):8414.
[17] Wu Z,Zhang Z,Gu C.Prognostic and clinicopathological impact of systemic inflammation response index(SIRI)on patients with esophageal cancer:A meta-analysis[J].Syst Rev,2025,14(1):104.
[18] Mengozzi A,Tricò D,Nesti L,et al.Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects:a cross-sectional and longitudinal analysis of the relationship between insulin sensitivity and cardiovascular risk(RISC)study cohort[J].Metabolism,2020,105:154185.
[19] Bergman M,Abdul-Ghani M,DeFronzo R A,et al.Review of methods for detecting glycemic disorders[J].Diabetes Res Clin Pract,2020,165:108233.
[20] Balke S,Weid P,Fangmann L,et al.Glucose levels of the oral glucose tolerance test(OGTT)can predict adverse pregnancy outcomes in women with gestational diabetes(GDM)[J].J Clin Med,2023,12(11):3709.
[21] Papachatzopoulou E,Chatzakis C,Lambrinoudaki I,et al.Abnormal fasting,post-load or combined glucose values on oral glucose tolerance test and pregnancy outcomes in women with gestational diabetes mellitus[J].Diabetes Res Clin Pract,2020,161:108048..
[22] Burt M G,Willenberg V M,Petersons C J,et al.Screening for diabetes in patients with inflammatory rheumatological disease administered long-term prednisolone:a cross-sectional study[J].Rheumatology(Oxford),2012,51(6):1112-1119.
[23] Kotzaeridi G,Blätter J,Eppel D,et al.Characteristics of gestational diabetes subtypes classified by oral glucose tolerance test values[J].Eur J Clin Invest,2021,51(9):e13628.
[24] Zou G.A modified poisson regression approach to prospective studies with binary data[J].Am J Epidemiol,2004,159(7):702-706.
[25] Sun T,Meng F,Zhao H,et al.Elevated first-trimester neutrophil count is closely associated with the development of maternal gestational diabetes mellitus and adverse pregnancy outcomes[J].Diabetes,2020,69(7):1401-1410.
[26] Yildiz E G,Tanacan A,Okutucu G,et al.Can system inflammation response index or systemic immune inflammation index predict gestational diabetes mellitus in the first trimester? A prospective observational study[J].Int J Gynaecol Obstet,2024,166(2):837-843.
[27] 王艺锦.妊娠早期全身免疫炎症指数和全身炎症反应指数与妊娠期糖尿病及母婴不良妊娠结局风险的关联性研究[D].宁夏医科大学,2025.
Wang Y J.Association between systemic immune inflammatory index and systemic inflammatory response index in early pregnancy and the risk of gestational diabetes mellitus and maternal and infant adverse pregnancy outcomes[D].Ningxia Med Univ,2025.
[28] Xie S,Zhang E,Gao S,et al.Associations of systemic immune-inflammation index and systemic inflammation response index with maternal gestational diabetes mellitus:evidence from a prospective birth cohort study[J].Chin Med J(Engl),2025,138(6):729-737.
[29] DeFronzo R A.From the triumvirate to the ominous octet:a new paradigm for the treatment of type 2 diabetes mellitus[J].Diabetes,2009,58(4):773-795.
[30] Stoikou M,Grimolizzi F,Giaglis S,et al.Gestational diabetes mellitus is associated with altered neutrophil activity[J].Front Immunol,2017,8:702.
[31] Mansuy-Aubert V,Zhou Q L,Xie X,et al.Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity,inflammation,and energy expenditure[J].Cell Metab,2013,17(4):534-548.
[32] Talukdar S,Oh D Y,Bandyopadhyay G,et al.Neutrophils mediate insulin resistance in high fat diet fed mice via secreted elastase[J].Nat Med,2012,18(9):1407-1412.
[33] Houghton A M,Rzymkiewicz D M,Ji H,et al.Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth[J].Nat Med,2010,16(2):219-223.
[34] Reyna S M,Ghosh S,Tantiwong P,et al.Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects[J].Diabetes,2008,57(10):2595-2602.
[35] Xie B G,Jin S,Zhu W J.Expression of toll-like receptor 4 in maternal monocytes of patients with gestational diabetes mellitus[J].Exp Ther Med,2014,7(1):236-240.
[36] Radin M S,Sinha S,Bhatt B A,et al.Inhibition or deletion of the lipopolysaccharide receptor toll-like receptor-4 confers partial protection against lipid-induced insulin resistance in rodent skeletal muscle[J].Diabetologia,2008,51(2):336-346.
[37] Sriwijitkamol A,Christ-Roberts C,Berria R,et al.Reduced s-keletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes:reversal by exercise training[J].Diabetes,2006,55(3):760-767.
[38] 李洁梅,伍莉,李娟华,等.孕早期血清微量元素水平与胆汁酸代谢及妊娠期糖尿病关联的巢式病例-对照研究[J].华中科技大学学报:医学版,2024,53(1):59-67.
Li J M,Wu L,Li J H, et al.Association of serum levels of trace elements in early pregnancy with bile acid metabolism and gestational diabetes mellitus:A nested case-control study[J].Acta Med Univ Sci Technol Huzhong,2024,53(1):59-67.
[39] Yang Y,Liu L,Liu B,et al.Functional defects of regulatory T cell through interleukin 10 mediated mechanism in the induction of gestational diabetes mellitus[J].DNA Cell Biol,2018,37(3):278-285.
[40] Tanaka T,Wada T,Uno K,et al.Oestrogen receptor α in T cells controls the T cell immune profile and glucose metabolism in mouse models of gestational diabetes mellitus[J].Diabetologia,2021,64(7):1660-1673.
[41] Sheu A,Chan Y,Ferguson A,et al.A proinflammatory CD4⁺T cell phenotype in gestational diabetes mellitus[J].Diabetologia,2018,61(7):1633-1643.
[42] 郑玉红,钟宏文,古菁华,等.妊娠期糖尿病患者外周血炎症指标与胰岛素抵抗相关性研究[J].临床医药实践,2025,34(2):126-130.
Zheng Y H,Zhong H W,Gu J H,et al.Correlation between peripheral blood inflammation and insulin resistance in patients with gestational diabetes mellitus[J].Clin Med Pract,2025,34(2):126-130.

孕早期全身炎症水平与妊娠期糖尿病发病风险的关联研究^*

Association between Systemic Inflammation in the First Trimester and the Risk of Gestational Diabetes Mellitus

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