Influence of Intrauterine Hyperglycemia Environment on Peripheral Inflammatory Response in Offspring of Gestational Diabetes Mellitus
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摘要:
目的 探讨妊娠期糖尿病（gestational diabetes mellitus ，GDM））宫内高血糖环境对子代脐血外周炎症反应的影响。 方法 选择2019年11月至2023年5月在昆明医科大学第一附属医院出生的GDM母亲及孕期血糖正常母亲的子代作为研究对象，其中选择孕期血糖控制良好的GDM组108例，男67例，女41例，对照组150例，男82例，女68例。采用流式CBA技术测定脐静脉血血清（IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-17、TNF-α、IFN-α、IFN-γ及IL-12P70）水平。 结果 GDM组脐静脉血血清IL-6、IL-8、TNF-α水平高于对照组，差异有统计学意义[（6.65±0.51） vs （4.02±0.40），P = 0.007；（13.96±1.10） vs （7.36±0.50），P = 0.040；（1.27±0.10） vs （0.56±0.01），P = 0.020]。GDM组IFN-γ水平低于对照组[（5.67±0.50） vs （10.54±0.90），P = 0.038]。GDM组脐静脉血血清IL-1β、IL-2、IL-4、IL-5、IL-10、IL-12P70、IL-17、IFN-α与对照组相比，差异无统计学意义（P > 0.05）。 结论 孕期血糖控制良好的GDM子代先天免疫系统仍被过度激活，并过度释放促炎症因子IL-6、IL-8、TNF-α，这将为进一步明确GDM宫内高血糖环境子代外周先天免疫系统被激活是否会诱导脑内神经炎症的发生的研究提供了临床依据及基础。 Abstract:Objective To explore the effect of intrauterine hyperglycemia on peripheral inflammatory reaction of cord blood of offspring with gestational diabetes mellitus（GDM）. Methods The objects of this study were the offspring of women who delivered in the first affiliated hospital of Kunming Medical University from November 2019 to May 2023．The GDM group included 108 infants（67 male cases and 41 female cases） of mothers with GDM．The control group included 150 infants（82 male cases and 68 female cases） of women with normal glucose tolerance.The concentrations of umbilical vein blood serum IL-1β, IL-2, IL-4, IL-5, IL-6, L-8, IL-10, IL-17, TNF-α, IFN-α, IFN-γ and IL-12P70 were measured by flow cytometry CBA technology. Results The levels of vein cord blood serum pro-inflammatory factors IL-6, IL-8 and TNF-α were higher than the control group, the differences was statistical （6.65±0.51 vs 4.02±0.40, P = 0.007; 13.96±1.10 vs 7.36±0.50, P = 0.040; 1.27±0.10 vs 0.56±0.01, P = 0.020）. The level of IFN-γ was lower than the control group（5.67±0.50 vs 10.54±0.90, P = 0.038）, the differences were statistical. There was no differences in the levels of IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12P70, IL-17, IFN-α. Conclusion Even in GDM offspring with good blood sugar control during pregnancy, the innate immune system is overactivated, and pro-inflammatory factors IL-6, IL-8, and TNF-α are released excessively, laying a clinical foundation for further understanding whether the activation of the peripheral innate immune system in the GDM intrauterine hyperglycemic environment can induce the occurrence of neuroinflammation in the brain and its contribution in neuroinflammation. -
Key words:
- Cord blood /
- Gestational diabetes mellitus /
- Offspring /
- Inflammatorresponse /
- Cytokine
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表 1 GDM组与对照组母亲人口统计学参数比较[（
$\bar x \pm s$ ）/n（%）]Table 1. Maternal demographics in GDM and control group[（
$\bar x \pm s$ ）/n（%）]参数 GDM
（n = 108）对照组
（n = 150）t/χ2 P 年龄（岁） 32 ± 3 30 ± 4 1.377 0.175 孕前体重（kg） 58.4 ± 7.5 53.2 ± 7.9 2.11 0.040* 身高（cm） 159 ± 5 161 ± 5 −0.882 0.382 孕前体质指数（kg/m2） 22.9 ± 2.7 20.5 ± 2.5 3.041 0.004* 分娩前体重（kg） 69.9 ± 8.3 66.1 ± 9.3 1.301 0.200 孕期增重（kg） 11.5 ± 6.3 12.9 ± 4.2 −0.950 0.347 民族 汉族 85（78.70） 120（80%） 1.399 0.597 少数民族 23（21.30） 30（20%） 孕次 1次 23（21.30） 56（37.30） 1.320 0.336 > 1次 85（78.70） 99（62.70） 产次 1次 77（71.3） 123（82.0） 2.576 0.108 > 1次 31（28.7） 27（18.0） 分娩方式 剖宫产 23（21.3） 30（20.0） 1.399 0.597 顺产 85（78.7） 120（80.0） *P < 0.05。 
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表 2 GDM组与对照组母亲孕期血糖水平比较（
$\bar x \pm s$ ）Table 2. Comparison of maternal blood glucose levels during pregnancy between GDM group and control group （
$\bar x \pm s$ ）血糖水平 GDM
（n = 108）对照组
（n = 150 ）t/t′ P OGTT （mmol/L） −0 h 5.08 ± 0.53 4.54 ± 0.31 4.372 < 0.001* −1 h 9.33 ± 1.57 7.03 ± 1.52 4.701 < 0.001* −2 h 7.96 ± 1.58 6.34 ± 0.96 4.369 < 0.001* 孕早中期HbA1c（%） 5.42 ± 0.19 4.92 ± 0.40 4.524 < 0.001* 孕晚期HbA1c（%） 5.19 ± 0.21 4.81 ± 0.36 4.562 < 0.001* *P<0.05。
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表 3 GDM组与对照组新生儿人体测量指标比较（
$ \bar x \pm s $ ）Table 3. Comparison of neonatal anthropometrics between GDM group and control group （
$ \bar x \pm s $ ）指标 GDM
（n = 108）对照组
（n = 150）t/t′ P 胎龄（周） 38.7 ± 1.1 39.2 ± 1.0 −1.472 0.953 出生体重（g） 3264 ± 330 3113 ± 383 1.290 0.646 身长（cm） 49.3 ± 1.3 49.3 ± 1.4 −0.088 0.716 头围（cm） 33.8 ± 1.3 33.5 ± 1.4 0.547 0.487
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表 4 GDM组与对照组脐静脉血清细胞因子水平比较（
$ \bar x \pm s $ ）Table 4. Comparison of serum cytokine levels in umbilical vein between GDM group and control group（
$ \bar x \pm s $ ）细胞因子
（pg/mL）GDM
（n = 108）对照组
（n = 150）t/t′ P IL-1β 3.64 ± 0.31 4.12 ± 0.30 −0.342 0.734 IL-2 0.84 ± 0.05 1.01 ± 0.04 −1.062 0.294 IL-4 0.72 ± 0.04 0.83 ± 0.02 −0.742 0.462 IL-5 1.37 ± 0.30 1.88 ± 0.08 −1.495 0.142 IL-8 13.96 ± 1.10 7.36 ± 0.50 2.009 0.040* IL-10 1.84 ± 0.05 1.67 ± 0.47 0.617 0.540 IL-6 6.65 ± 0.51 4.02 ± 0.40 1.218 0.007* IL-12P70 0.84 ± 0.02 0.93 ± 0.01 −0.788 0.435 IL-17 1.54 ± 0.08 2.22 ± 0.20 −1.107 0.274 IFN-α 0.89 ± 0.05 1.41 ± 0.08 −1.364 0.179 IFN-γ 5.67 ± 0.50 10.54 ± 0.90 −2.140 0.038* TNF-α 1.27 ± 0.10 0.56 ± 0.01 0.313 0.020* *P < 0.05。
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表 5 GDM组脐静脉血与脐动脉血血清细胞因子水平比较（
$ \bar x \pm s $ ）Table 5. Comparison of serum cytokine levels between umbilical vein blood and umbilical artery blood in GDM group （
$ \bar x \pm s $ ）细胞因子
（pg/mL）脐静脉GDM
（n = 30）脐动脉GDM
（n = 30）t/t′ P IL-1β 3.76 ± 0.40 6.03 ± 0.60 −0.911 0.392 IL-2 0.47 ± 0.03 0.36 ± 0.02 1.142 0.291 IL-4 0.40 ± 0.04 0.42 ± 0.03 −0.923 0.387 IL-5 1.15 ± 0.08 0.67 ± 0.03 1.095 0.310 IL-8 14.34 ± 0.90 15.11 ± 0.60 −1.621 0.149 IL-10 2.20 ± 0.30 2.05 ± 1.07 1.113 0.303 IL-6 8.51 ± 0.60 7.97 ± 0.90 −2.182 0.065 IL-12P70 0.68 ± 0.03 0.57 ± 0.01 1.995 0.086 IL-17 1.09 ± 0.07 1.15 ± 0.04 −0.840 0.429 IFN-α 0.53 ± 0.02 0.59 ± 0.01 −0.653 0.534 IFN-γ 4.01 ± 0.60 3.97 ± 0.30 0.138 0.894 TNF-α 1.28 ± 0.09 1.00 ± 0.03 1.011 0.346
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表 6 对照组脐静脉血与脐动脉血血清细胞因子水平比较（
$ \bar x \pm s $ ）Table 6. Comparison of serum cytokine levels between umbilical vein blood and umbilical artery blood in the control group （
$ \bar x \pm s $ ）细胞因子
（pg/mL）脐静脉对照组
（n = 34）脐动脉对照组
（n = 34）t/t′ P IL-1β 5.45 ± 0.30 7.40 ± 0.50 −0.612 0.553 IL-2 0.49 ± 0.03 0.49 ± 0.02 0.022 0.983 IL-4 0.38 ± 0.02 0.40 ± 0.03 −2.11 0.059 IL-5 1.79 ± 0.10 1.74 ± 1.47 0.137 0.893 IL-8 7.75 ± 0.10 8.26 ± 0.30 −2.214 0.051 IL-10 2.09 ± 0.08 2.10 ± 0.06 −0.115 0.911 IL-6 6.30 ± 0.40 5.06 ± 0.3 −2.232 0.052 IL-12P70 0.63 ± 0.06 0.65 ± 0.03 −0.429 0.676 IL-17 0.89 ± 0.01 0.93 ± 0.02 −0.626 0.544 IFN-α 0.41 ± 0.02 0.59 ± 0.03 −1.050 0.316 IFN-γ 3.41 ± 0.20 4.17 ± 0.21 −2.068 0.063 TNF-α 0.55 ± 0.03 0.63 ± 0.02 −0.345 0.737
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