血浆CMPF水平诊断妊娠期糖尿病的临床价值

Clinical values of plasma CMPF level in diagnosis of gestational diabetes mellitus

目的探讨血浆3-羧基-4-甲基-5-丙基-2-呋喃丙酸(CMPF)水平诊断妊娠期糖尿病(GDM)的临床价值。方法选取2016年1月至2017年6月,于上海交通大学附属第六人民医院就诊的60例孕妇为研究对象,按照是否合并GDM,将其分为GDM组(n=40)和对照组(n=20)。所有孕妇于中孕期(孕龄为13～18孕周),进行生化指标检测;于孕龄为24～28孕周时,进行口服葡萄糖耐量试验(OGTT)检查,同时利用超高效液相色谱-三重四极杆质谱联用技术,检测孕妇血浆CMPF水平。采用成组t检验,对2组孕妇孕龄为28孕周及新生儿足月时人体质量指数(BMI),以及高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、总蛋白、白蛋白、尿素、尿酸水平等指标进行比较。采用Mann-Whitney U检验,对2组孕妇的孕龄、孕次、产次、血浆CMPF水平、孕龄为18孕周时BMI及糖化血红蛋白(HbA1c)、糖化白蛋白(GA)、肌酐水平等指标进行比较。采用多因素非条件logistic回归分析,对孕妇发生GDM的影响因素进行分析。绘制血浆CMPF水平及孕龄为18、28孕周时BMI诊断GDM的受试者工作特征(ROC)曲线,以及这3个指标联合诊断与OGTT 0、1、2h血糖浓度联合诊断GDM的ROC,并计算ROC曲线下面积(ROC-AUC)。本研究遵循的程序符合上海交通大学附属第六人民医院人体试验委员会制定的伦理学标准,并经过该伦理委员会批准(审批文号:2017-012),分组征得2组受试者知情同意,并与之签署临床研究知情同意书。结果 (1)2组孕妇的孕龄、孕次和产次等一般临床资料比较,差异均无统计学意义(P>0.05)。(2)GDM组血浆CMPF值为522.0ng/mL(326.9～989.3ng/mL),显著高于对照组的280.2ng/mL(177.8～466.6ng/mL),2组比较,差异有统计学意义(U=576.000,P=0.006)。(3)GDM组孕妇孕龄为18、28孕周及新生儿足月时BMI与HbA1c分别为24.6kg/m^2(22.0～25.9kg/m^2)、(26.1±2.8)kg/m^2、(27.6±2.9)kg/m^2、5.4%(5.3%～5.6%),均显著高于对照组的22.8kg/m^2(20.1～23.6kg/m^2)、(24.5±2.6)kg/m^2、(25.5±2.6)kg/m^2、5.2%(5.0%～5.3%),并且差异均有统计学意义(U=568.000,P=0.002;t=2.150,P=0.001;t=1.180,P=0.036;U=226.000,P<0.001)。GDM组孕妇GA值为11.6%(10.8%～12.8%),低于对照组的12.6%(12.2%～13.2%),并且差异亦有统计学意义(U=248.000,P=0.017)。(4)对孕妇发生GDM影响因素进行多因素非条件logistic回归分析的结果显示,血浆CMPF水平及孕龄为18、28孕周时BMI,均为孕妇发生GDM的独立影响因素(OR=1.003,95%CI:1.000～1.005,P=0.023;OR=4.393,95%CI:1.675～11.525,P=0.003;OR=0.322,95%CI:0.130～0.798,P=0.014)。(5)通过ROC曲线分析结果显示,血浆CMPF水平及孕龄为18、28孕周时BMI诊断GDM的ROC-AUC分别为0.703(95%CI:0.554～0.852,P=0.014),0.741(95%CI:0.605～0.876,P=0.004)及0.672(95%CI:0.523～0.821,P=0.039)。这3个指标联合诊断GDM的ROC-AUC为0.847(95%CI:0.741～0.952,P<0.001),与OGTT 0、1、2h血糖浓度联合诊断GDM的ROC-AUC[0.983(95%CI:0.957～1.000,P<0.001)]比较,差异无统计学意义(U=9.000,P=0.100)。根据约登指数最大原则,血浆CMPF水平及孕龄为18、28孕周时BMI诊断GDM的最佳临界值分别为397.2ng/mL、23.9kg/m^2、26.2kg/m^2,此时其诊断GDM的敏感度分别为65.6%、59.4%、53.1%,特异度分别为75.0%、90.0%、80.0%。结论 GDM孕妇孕龄为24～28孕周时血浆CMPF水平联合孕龄为18、28孕周时BMI,对GDM诊断具有较好临床价值。

Objective To investigate clinical values of plasma 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid(CMPF)level in diagno sis of gestational diabetes mellitus(GDM).Methods A total of 60 pregnant women who admitted into Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from January 2016 to June 2017 were selected as the study subjects.They were divided into GDM group(n=40)and control group(n=20)according to whether they were combined with GDM or not.All pregnant women were tested for biochemical markers during 13 to 18 gestational weeks.And 75 g oral glucose tolerance test(OGTT)was performed during 24 to 28 gestational weeks.At the same time,ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to detect plasma CMPF level.The body mass index(BMI)at 28 gestational weeks and at neonatal term,high-density lipoprotein(HDL),low-density lipoprotein(LDL),total protein,albumin,urea,and uric acid were compared between two groups by independent-samples t test.Gestational age,gravidity,parity,plasma CMPF level,BMI at 18 gestational weeks,hemoglobin A1c(HbA1c),glycated albumin(GA),creatinine and other indicators between two groups were compared by Mann-Whitney U test.Multiple unconditional logistic regression analysis was used to analyze the influencing factors of GDM in pregnant women.The receiver operating characteristics(ROC)curves for plasma CMPF level and BMI at 18,28 gestational weeks,and the combination these 3 factors,and the combination of OGTT 0,1,2 h blood glucose concentrations in diagnosis of GDM were built respectively,and the area under ROC curve(ROC-AUC)of them were calculated.The procedures followed in this study were in accordance with the ethical standards established by the Human Subjects Trial Committee of the Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University,and this study was approved by this committee(approval number:2017-012).Informed consent was obtained and signed with each subject.Results①There was no significant difference in the general clinical data such as gestational age,gravidity and parity between two groups(P>0.05).②The plasma CMPF level of GDM group was 522.0 ng/mL(326.9-989.3 ng/mL),which was significantly higher than that of control group 280.2 ng/mL(177.8-466.6ng/mL).The difference between two groups was statistically significant(U=576.000,P=0.006).③BMI at 18,28 gestational weeks and at neonatal term,and HbA1c in GDM group were 24.6 kg/m^2(22.0-25.9 kg/m^2),(26.1±2.8)kg/m^2,(27.6±2.9)kg/m^2,and 5.4%(5.3%-5.6%),respectively,which were significantly higher than those in control group 22.8 kg/m^2(20.1-23.6 kg/m 2),(24.5±2.6)kg/m^2,(25.5±2.6)kg/m 2,5.2%(5.0%-5.3%),and all the differences were statistically significant(U=568.000,P=0.002;t=2.150,P=0.001;t=1.180,P=0.036;U=226.000,P<0.001).The GA in GDM group was 11.6%(10.8%-12.8%),which was significantly lower than that in control group 12.6%(12.2%-13.2%),and the difference was also statistically significant(U=248.000,P=0.017).④The results of multiple unconditional logistic regression analysis of the influencing factors of GDM in pregnant women showed that plasma CMPF levels and BMI at 18,28 gestational weeks were independent influencing factors of GDM in pregnant women(OR=1.003,95%CI:1.000-1.005,P=0.023;OR=4.393,95%CI:1.675-11.525,P=0.003;OR=0.322,95%CI:0.130-0.798,P=0.014).⑤The results of ROC curve analysis showed that the ROC-AUC of plasma CMPF level,BMI at 18,28 gestational weeks in diagnosis of GDM were 0.703(95%CI:0.554-0.852,P=0.014),0.741(95%CI:0.605-0.876,P=0.004),and 0.672(95%CI:0.523-0.821,P=0.039),respectively.The ROC-AUC of plasma CMPF level combined with BMI at 18 and 28 gestational weeks in diagnosis of GDM was 0.847(95%CI:0.741-0.952,P<0.001),and the ROC-AUC of combination of OGTT 0,1,2 h blood glucose concentrations in diagnosis of GDM was 0.983(95%CI:0.957-1.000,P<0.001),and there was no statistically significant difference between them(U=9.000,P=0.100).According to the maximum principle of Youden index,the best cut-off values of plasma CMPF level and BMI at 18,28 gestational weeks for diagnosis of GDM were 397.2 ng/mL,23.9 kg/m^2,26.2 kg/m^2,respectively,and the sensitivities of them in diagnosis of GDM were 65.6%,59.4%and 53.1%,respectively,and the specificities were 75.0%,90.0%and 80.0%,respectively.Conclusion The plasma CMPF level at 24 to 28 gestational weeks combined with BMI at 18 and 28 gestational weeks has a good clinical diagnostic value for GDM.