妊娠早期血清betatrophin和纤维凝胶蛋白-3对妊娠期糖尿病的预测价值分析

Analysis of the predictive value of serum betatrophin and fibrin-3 during early pregnancy for gestational diabetes mellitus

目的探讨妊娠早期孕妇血清betatrophin、纤维凝胶蛋白-3(ficolin-3)对妊娠期糖尿病(GDM)的预测价值。方法采用前瞻性的研究方法,选取昆明市延安医院2018年6月至2019年6月行产前检查的孕7~13周孕妇作为研究对象并预留空腹外周静脉血标本,于孕24~28周行口服75 g葡萄糖耐量试验(OGGT)检查,其中65例诊断为GDM(GDM组),选取年龄和孕周匹配的60例结果正常孕妇作为正常组。另外,再选取同期年龄匹配的非妊娠健康女性体检者60例作为对照组。采用酶联免疫吸附试验法检测GDM组、正常组孕7~13周及对照组血清betatrophin和ficolin-3水平,采用Pearson检验分析血清betatrophin和ficolin-3与孕24~28周糖脂代谢指标的相关性,采用受试者工作特征(ROC)曲线分析妊娠早期孕妇血清betatrophin和ficolin-3对GDM的预测价值。结果GDM组血清betatrophin和ficolin-3明显高于正常组和对照组[(35.69±6.15)ng/L比(23.90±7.68)和(19.68±6.33)ng/L、(31.75±10.30)μg/L比(22.88±12.71)和(18.47±9.54)μg/L],正常组血清betatrophin和ficolin-3水平明显高于对照组,差异均有统计学意义(P<0.05)。相关性分析结果显示,孕妇血清betatrophin与总胆固醇(TC)、糖化血红蛋白(HbA1c)和稳态模型评估法胰岛素抵抗指数(HOMA-IR)呈正相关(r=0.585、0.440和0.735,P<0.01);血清ficolin-3与HbA1c呈正相关(r=0.673,P<0.01),与高密度脂蛋白胆固醇(HDL-C)呈负相关(r=-0.520,P<0.01)。ROC曲线分析结果显示,betatrophin和ficolin-3预测GDM的曲线下面积为0.829和0.795,95%CI 0.753~0.905和0.718~0.872,最佳临界值27.69 ng/L和29.72μg/L,灵敏度为89.36%和84.58%,特异度为72.14%和79.64%,约登指数为0.62和0.59。两者联合检测预测GDM的AUC为0.923,95%CI 0.868~0.978,灵敏度为91.25%,特异度为87.24%,约登指数为0.86。结论GDM孕妇在妊娠早期血清betatrophin和ficolin-3已存在表达异常,且与糖脂代谢指标相关,妊娠早期血清betatrophin和ficolin-3对GDM有一定预测价值。

Objective To explore the predictive value of serum betatrophin and ficolin-3 during early pregnancy for gestational diabetes mellitus(GDM).Methods Using a prospective research method,from June 2018 to June 2019,7 to 13 weeks pregnant women were selected in Yan′an Hospital of Kunming City,and their fasting peripheral venous blood samples were reserved.At 24 to 28 weeks of pregnancy,oral glucose tolerance test(OGGT)was performed.Sixty-five cases were diagnosed as GDM(GDM group),and 60 pregnant women with normal OGGT result and matched age and gestational weeks were selected as normal group.In addition,60 non-pregnant healthy women with matched age were selected as control group.The serum levels of betatrophin and ficolin-3 were measured in GDM group,normal control group(during 7 to 13 weeks of gestation)and control group were measured by enzyme linked immunosorbent assay method.Pearson test was used to analyze the correlation between serum betatrophin,ficolin-3 and glycolipid metabolism indexes during 24 to 28 weeks of gestation.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum betatrophin and ficolin-3 during early pregnancy for GDM.Results The serum betatrophin and ficolin-3 in GDM group were significantly higher than those in normal group and control group:(35.69±6.15)ng/L vs.(23.90±7.68)and(19.68±6.33)ng/L,(31.75±10.30)μg/L vs.(22.88±12.71)and(18.47±9.54)μg/L,the betatrophin and ficolin-3 in normal group were significantly higher than those in control group,and there were statistical differences(P<0.05).The correlation analysis result showed that serum betatrophin was positive correlation with total cholesterol(TC),glycosylated hemoglobin(HbA1c)and homeostatic model assessment insulin resistance index(HOMA-IR)(r=0.585,0.440 and 0.735;P<0.01);the serum ficolin-3 was positively correlated with HbA1c(r=0.673,P<0.01),and negatively correlated with high-density lipoprotein cholesterol(HDL-C)(r=-0.520,P<0.01).ROC curve analysis result showed that the areas under curve of betatrophin and ficolin-3 for predicting GDM were 0.829 and 0.795,95%CI 0.753 to 0.905 and 0.718 to 0.872,and the optimum critical values were 27.69 ng/L and 29.72μg/L,with a sensitivity of 89.36%and 84.58%,a specificity of 72.14%and 79.64%and Yorden index of 0.62 and 0.59.The areas under curve of betatrophin combined with ficolin-3 for predicting GDM was 0.923,95%CI 0.868 to 0.978,with a sensitivity of 91.25%,a specificity of 87.24%and Yorden index of 0.86.Conclusions GDM pregnant women have abnormal expression of serum betatrophin and ficolin-3 during early pregnancy,and the indexes are related to glycolipid metabolism.Serum betatrophin and ficolin-3 during early pregnancy have certain predictive value for GDM.