The Relationship Between Serum CTRP7 and CTRP15 Levels and Insulin Resistance and Maternal and Neonatal Outcomes in Patients with Gestational Diabetes Mellitus
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摘要:
目的 探讨妊娠糖尿病患者血清C1q/肿瘤坏死因子相关蛋白7（complement c1q/tnf related proteins7，CTRP7）和CTRP15水平与胰岛素抵抗及母婴结局的关系。 方法 选取2023年1月至2024年5月入同济大学附属妇产科医院诊断为妊娠糖尿病患者139例为妊娠糖尿病组，根据母婴结局分为GDM结局正常组（n = 91）和GDM结局不良组（n = 48），另选取同期孕检健康孕妇100例为健康孕妇组。采用酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）法检测血清CTRP7和CTRP15水平，Pearson相关分析血清CTRP7、 CTRP15水平与胰岛素抵抗及血糖、血脂的相关性，Logistic回归分析母婴不良结局因素。 结果 娠糖尿病组孕期体重增加、胎盘重量、绒毛膜炎占比、HOMA-IR、FBG、TG、TC、LDL-C、FPG、FINS、HbAlc水平明显高于健康孕妇组， 健康膳食占比、运动占比、HOMA-β低于健康孕妇组（P < 0.05）；妊娠糖尿病组患者血清CTRP7和CTRP15水平明显高于健康孕妇组（P < 0.05）；血清CTRP7和CTRP15水平与HOMA-IR、FBG、TG、TC、LDL-C、FPG、FINS和HbAlc呈正相关性（P < 0.05），与HOMA-β呈负相关性（P < 0.05）；GDM结局不良组孕期体重增加、绒毛膜炎占比、HOMA-IR、FBG、TG、TC、LDL-C、FPG、FINS、HbAlc水平显著高于GDM结局正常组，HOMA-β显著低于GDM结局正常组（P < 0.05）。孕期体重增加、绒毛膜炎、HOMA-IR、HOMA-β、FBG、TG、TC、LDL-C、FPG、FINS、HbAlc、CTRP7和CTRP15均是妊娠糖尿病患者母婴不良结局的影响因素（P < 0.05），三者联合预测价值明显高于三者单独检测（Z = 4.265、3.612、3.954，P < 0.001）。 结论 妊娠糖尿病患者血清中CTRP7和CTRP15水平明显升高，且与胰岛素抵抗密切相关，与HOMA-IR联合检测对不良母婴结局具有一定预测价值。 Abstract:Objective To investigate the relationship between serum C1q/tumor necrosis factor-related protein 7 （complement c1q/tnf related proteins7, CTRP7） and CTRP15 levels and insulin resistance （Insulin resistance） as well as maternal and neonatal outcomes in patients with gestational diabetes mellitus. Methods A total of 139 patients diagnosed with gestational diabetes at the Obstetrics and Gynecology Hospital Affiliated to Tongji University from January 2023 to May 2024 were selected as the gestational diabetes group. Based on maternal and neonatal outcomes, they were divided into a GDM with normal outcomes group （91 cases） and a GDM with adverse outcomes group （48 cases）. Additionally, 100 healthy pregnant women who underwent prenatal check-ups during the same period were selected as the healthy pregnant women group. The serum levels of CTRP7 and CTRP15 were measured using the enzyme-linked immunosorbent assay （ELISA） method. Pearson correlation analysis was used to analyze the correlation between serum CTRP7 and CTRP15 levels and insulin resistance, blood glucose, and blood lipids. Logistic regression analysis was used to analyze the factors associated with adverse maternal and neonatal outcomes. Results The GDM group had significantly higher levels of gestational weight gain, placental weight, proportion of chorioamnionitis, HOMA-IR, FBG, TG, TC, LDL-C, FPG, FINS, and HbA1c compared to the healthy pregnant women group, while the proportions of healthy diet and exercise, and HOMA-β were lower than those in the healthy pregnant women group （P < 0.05）. The serum levels of CTRP7 and CTRP15 in the GDM group were significantly higher than those in the healthy pregnant women group（P < 0.05）. Serum CTRP7 and CTRP15 levels were positively correlated with HOMA-IR, FBG, TG, TC, LDL-C, FPG, FINS, and HbA1c （P < 0.05）, and negatively correlated with HOMA-β （P < 0.05）. The GDM with adverse outcomes group had significantly higher levels of gestational weight gain, proportion of chorioamnionitis, HOMA-IR, FBG, TG, TC, LDL-C, FPG, FINS, and HbA1c compared to the GDM with normal outcomes group, while HOMA-β was significantly lower than that in the GDM with normal outcomes group （P<0.05）. Maternal weight gain during pregnancy, chorioamnionitis, HOMA-IR, HOMA-β, FBG, TG, TC, LDL-C, FPG, FINS, HbAlc, CTRP7, and CTRP15 are all influencing factors for adverse maternal and neonatal outcomes in patients with gestational diabetes mellitus （P<0.05）. The combined predictive value of the three is significantly higher than that of each alone （Z=4.265, 3.612, 3.954, P<0.001）. Conclusion Serum levels of CTRP7 and CTRP15 are significantly elevated in patients with gestational diabetes mellitus （GDM） and are closely related to insulin resistance. Combined detection with HOMA-IR has certain predictive value for adverse maternal and infant outcomes. -
Key words:
- Gestational diabetes mellitus /
- CTRP7 /
- CTRP15 /
- Insulin resistance /
- Maternal and infant outcome
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图 1 HOMA-IR、CTRP7和CTRP15 单独及联合预测母婴结局的ROC 曲线
Figure 1. ROC curves for HOMA-IR，CTRP7，and CTRP15 alone and in combination in predicting maternal and neonatal outcomes
表 1 两组患者的临床资料对比分析[（$\bar x\pm s $ ）/n（%）]
Table 1. Comparative analysis of clinical data between the two groups of patients[（ $\bar x\pm s $）/n（%）]
组别 健康孕妇组（n=100） 妊娠糖尿病组（n=139） t P 年龄（岁） 28.09 ± 4.19 29.11 ± 4.21 1.851 0.065 孕前 BMI（kg/m2） 21.52 ± 2.27 22.04 ± 2.34 1.716 0.087 增加 BMI（kg/m2） 3.56 ± 1.27 3.81 ± 1.32 1.461 0.143 孕周（周） 26.61 ± 2.23 26.84 ± 2.81 0.679 0.498 收缩压（mmHg） 110.56 ± 10.19 112.81 ± 10.24 1.679 0.094 舒张压（mmHg） 70.78 ± 5.64 72.04 ± 8.13 1.355 0.183 孕期体重增加（kg） 11.75 ± 5.16 13.89 ± 6.07 2.859 0.005* 膳食结构 高盐高油膳食 10（10.00） 35（25.18） 8.901 0.012* 高脂膳食 18（18.00） 23（16.55） 健康膳食 72（72.00） 81（58.27） 体力活动 运动 69（69.00） 74（53.24） 6.013 0.014* 不运动 31（31.00） 65（46.76） 胎盘重量（g） 510.29 ± 9.87 517.86 ± 11.32 5.376 < 0.001* 绒毛膜炎 0（0.00） 13（9.35） 9.89 0.002* HOMA-IR 2.34 ± 0.49 4.61 ± 1.08 19.608 < 0.001* FBG（mmol/L） 4.29 ± 0.97 6.50 ± 1.03 16.764 < 0.001* TG（mmol/L） 2.63 ± 0.73 3.82 ± 0.81 11.671 < 0.001* TC（mmol/L） 5.29 ± 0.78 6.48 ± 0.80 11.463 < 0.001* HDL-C（mmol/L） 1.64 ± 0.42 1.69 ± 0.46 0.859 0.391 LDL-C（mmol/L） 2.61 ± 0.56 3.17 ± 0.74 6.367 < 0.001* FPG（mmol/L） 4.68 ± 0.25 5.56 ± 0.37 20.63 < 0.001* FINS（mU/L） 12.82 ± 3.51 15.29 ± 3.42 5.447 < 0.001* HbAlc（%） 4.79 ± 0.57 5.94 ± 0.82 12.078 < 0.001* ALB（ng/ml） 38.28 ± 2.93 38.33 ± 2.97 0.129 0.897 Hb（g/L） 115.93 ± 15.18 117.42 ± 15.26 0.746 0.456 *P < 0.05。 
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表 2 两组患者血清CTRP7和CTRP15水平对比分析[（ $\bar x\pm s $）/n（%）]
Table 2. Comparative analysis of serum CTRP7 and CTRP15 levels between the two patient groups[（$\bar x\pm s $）/n（%）]
组别 n CTRP7（μg/L） CTRP15（μg/L） 健康孕妇组 100 109.58 ± 27.36 35.69 ± 9.45 妊娠糖尿病组 139 184.26 ± 31.42 73.21 ± 18.37 t 19.117* 18.713* P < 0.001 < 0.001 *P < 0.05。
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表 3 血清CTRP7、CTRP15水平与血糖、血脂及胰岛素抵抗的关系
Table 3. Relationship between serum CTRP7 and CTRP15 levels with blood glucose，blood lipids，and insulin resistance
指标 CTRP7 CTRP15 r P r P HOMA-IR 0.475 < 0.001* 0.492 < 0.001* FBG 0.319 < 0.001* 0.325 < 0.001* TG 0.392 < 0.001* 0.403 < 0.001* TC 0.407 < 0.001* 0.418 < 0.001* LDL-C 0.519 < 0.001* 0.426 < 0.001* FPG 0.391 < 0.001* 0.381 < 0.001* FINS 0.474 < 0.001* 0.417 < 0.001* HbAlc 0.501 < 0.001* 0.434 < 0.001* *P < 0.05。
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表 4 不同母婴结局患者临床资料对比分析[（$\bar x\pm s $）/n（%）]
Table 4. Comparative analysis of clinical data among patients with different maternal-infant outcomes[（$\bar x\pm s $）/n（%）]
组别 GDM结局正常组（n=91） GDM结局不良组（n=48） t P 年龄（岁） 28.75 ± 4.16 29.64 ± 4.25 1.19 0.236 孕前 BMI（kg/m2） 21.72 ± 2.29 22.37 ± 2.38 1.569 0.119 增加 BMI（kg/m2） 3.65 ± 1.28 3.83 ± 1.36 0.735 0.464 孕周（周） 26.73 ± 2.41 26.95 ± 2.92 0.475 0.636 收缩压（mmHg） 112.75 ± 9.47 114.93 ± 8.02 1.358 0.177 舒张压（mmHg） 71.49 ± 6.73 72.21 ± 8.57 0.544 0.587 孕期体重增加（kg） 12.29 ± 5.18 14.63 ± 6.26 2.353 0.020* 膳食结构 高盐高油膳食 21（23.08） 14（29.17） 0.676 0.713 高脂膳食 15（16.48） 8（16.67） 健康膳食 55（60.44） 26（54.17） 体力活动 运动 51（56.04） 23（47.92） 0.834 0.361 不运动 40（43.96） 25（52.08） 胎盘重量（g） 516.27 ± 10.98 519.35 ± 11.49 1.549 0.124 绒毛膜炎 5（5.49） 8（16.67） 4.627 0.031* HOMA-IR 3.79 ± 0.84 5.72 ± 1.25 10.821 < 0.001* FBG（mmol/L） 5.22 ± 0.99 6.76 ± 1.18 8.152 < 0.001* TG（mmol/L） 2.92 ± 0.79 4.18 ± 0.92 8.44 < 0.001* TC（mmol/L） 5.73 ± 0.75 6.96 ± 0.89 8.61 < 0.001* HDL-C（mmol/L） 1.66 ± 0.44 1.71 ± 0.49 0.612 0.541 LDL-C（mmol/L） 2.78 ± 0.61 3.39 ± 0.82 4.961 < 0.001* FPG（mmol/L） 4.73 ± 0.29 5.94 ± 0.45 19.207 < 0.001* FINS（mU/L） 13.72 ± 3.27 16.84 ± 3.62 5.153 < 0.001* HbAlc（%） 4.92 ± 0.59 6.24 ± 0.91 10.333 < 0.001* ALB（ng/ml） 38.31 ± 2.94 38.35 ± 3.01 0.076 0.939 Hb（g/L） 115.99 ± 15.20 117.83 ± 15.32 0.677 0.499 *P < 0.05。
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表 5 不同母婴结局患者血清CTRP7、 CTRP15水平对比分析（$\bar x\pm s $ ）
Table 5. Comparative analysis of serum CTRP7 and CTRP15 levels in patients with different maternal-infant outcomes（ $\bar x\pm s $）
组别 n CTRP7（μg/L） CTRP15（μg/L） GDM 结局正常组 91 123.84 ± 28.47 47.84 ± 12.43 GDM 结局不良组 48 192.18 ± 32.39 82.67 ± 20.55 t 12.824* 12.439* P < 0.001 < 0.001 *P < 0.05。
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表 6 Logistic回归分析母婴不良妊娠结局因素
Table 6. Logistic regression analysis of factors associated with adverse maternal and fetal pregnancy outcomes
因素 β SE Wald χ2 P OR 95%CI 孕期体重增加 1.046 0.319 9.469 0.001* 2.846 1.523-5.318 绒毛膜炎 1.217 0.347 9.697 0.001* 3.377 1.710-6.666 HOMA-IR 1.034 0.321 9.411 0.002* 2.812 1.499-5.275 FBG 0.871 0.219 10.167 < 0.001* 2.389 1.555-3.670 TG 1.164 0.382 9.237 0.003* 3.203 1.514-6.771 TC 1.627 0.231 13.233 < 0.001* 5.089 3.235-8.002 LDL-C 1.521 0.396 10.031 < 0.001* 4.577 2.106-9.945 FPG 0.853 0.327 8.799 0.010* 2.347 1.236-4.454 FINS 1.436 0.316 10.734 < 0.001* 4.204 2.262-7.809 HbAlc 0.791 0.332 8.573 0.019* 2.206 1.150-4.227 CTRP7 1.384 0.216 12.597 < 0.001* 3.991 2.613-6.094 CTRP15 1.075 0.278 10.057 < 0.001* 2.93 1.699-5.052 *P < 0.05。
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表 7 HOMA-IR、CTRP7和CTRP15 单独及联合预测母婴结局的价值分析
Table 7. Value analysis of HOMA-IR，CTRP7，and CTRP15 alone and in combination for predicting maternal and neonatal outcomes
预测项目 AUC值 95%CI 敏感度% 特异度% 约登指数 截断值 HOMA-IR 0.701 0.602-0.799 70.83 78.39 0.492 4.03 CTRP7 0.812 0.729-0.884 83.33 71.56 0.549 146.78 μg/L CTRP15 0.803 0.712-0.893 81.25 72.44 0.537 63.22 μg/L 联合检测 0.893 0.837-0.949 91.67 67.25 0.589 −
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