孕早期空腹血糖联合脂联素、白细胞介素6、肿瘤坏死因子-α基因多态性与围孕期胰岛素抵抗的关联

Association between fasting blood glucose combined with gene polymorphisms of adiponectin,interleukin 6 and tumor necrosis factor-alpha in early pregnancy and insulin resistance in peri-pregnancy

目的探讨孕早期空腹血糖(FPG)及脂联素(ADIPOQ)、白细胞介素6(IL-6)及肿瘤坏死因子-α(TNF-α)基因多态性与妊娠期糖尿病(GDM)患者围孕期胰岛素抵抗的关系。方法回顾性选取济宁医学院附属医院2022年1—8月收治的在妊娠24~28周被确诊为GDM的60例患者(GDM组)和同期60例健康孕妇(健康对照组)为研究对象。两组均在孕8~12周检测空腹胰岛素(FINS)、FPG,计算稳态模型胰岛素抵抗指数(HOMA-IR)。同时采用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)技术检测血清ADIPOQ基因S01000622位点、IL-6基因S01006318位点及TNF-α基因S01009718位点基因多态性,采用受试者工作特征(ROC)曲线评估孕早期FPG联合ADIPOQ、IL6及TNF-α基因多态性预测GDM的诊断效能。结果GDM组体质量指数(BMI)、孕早期FPG、孕中期FPG、75 g口服葡萄糖耐量试验(OGTT)1 h血糖、OGTT 2 h血糖、糖化血红蛋白(HbA1c)、FINS及HOMA-IR均高于健康对照组[(27.1±2.6)kg/m^(2)比(25.6±2.5)kg/m^(2)、(4.7±1.3)mmol/L比(4.1±1.5)mmol/L、(5.5±1.3)mmol/L比(4.2±1.2)mmol/L、(6.3±1.5)mmol/L比(5.5±1.7)mmol/L、(6.0±1.5)mmol/L比(5.2±1.4)mmol/L、(5.8±0.7)%比(5.2±0.6)%、(6.4±1.1)mU/L比(5.2±1.2)mU/L、1.5±0.6比1.0±0.7],差异有统计学意义(P<0.05)。根据基因型的风险评估,GDM组中高危风险率为88.33%(53/60),健康对照组为56.67%(34/60),两组比较差异有统计学意义(χ^(2)=17.67,P<0.05)。GDM患者ADIPOQ基因S01000622位点TG基因型患者HOMA-IR高于TT基因型患者(6.58±0.89比4.98±0.58),IL-6基因S01006318位点CG基因型HOMA-IR高于CC、GG基因型患者(8.13±1.31比6.53±0.81、4.85±0.54),TNF-α基因S01009718位点AG基因型患者HOMA-IR高于GG基因型患者(6.31±1.04比5.16±0.82),差异均有统计学意义(P<0.05)。Logistic回归分析显示,年龄>35岁、既往糖尿病病史、BMI、ADIPOQ基因S01000622位点TG基因型、IL-6基因S01006318位点CG基因型、TNF-α基因S01009718位点AG基因型均是影响GDM发病的独立危险因素(P<0.05)。受试者工作特征(ROC)曲线分析结果显示,FPG预测GDM发病的曲线下面积(AUC)为0.737,特异度为83.50%;FPG联合ADIPOQ、IL-6、TNF-α基因风险评估预测GDM发病的AUC为0.921,特异度为86.80%。结论ADIPOQ基因S01000622位点TG基因型、IL-6基因S01006318位点CG基因型、TNF-α基因S01009718位点AG基因型与GDM发病具有一定相关性,能够预测GDM发病且与患者围孕期胰岛素抵抗相关,早期FPG检测联合遗传基因筛查对于降低母儿不良妊娠结局有现实临床指导意义。

Objective To study the relationship between fasting glucose(FPG)and gene polymorphisms of adiponectin(ADIPOQ),interleukin 6(IL-6)and tumor necrosis factor-alpha(TNF-α)in early pregnancy and insulin resistance in patients with gestational diabetes mellitus(GDM).Methods Sixty patients diagnosed with GDM within 24-28 weeks from January 2022 to August 2022 in the Affiliated Hospital of Jining Medical University were selected as the GDM group,and another 60 healthy pregnant women were taken as the normal control group.The fasting insulin(FINS),FPG levels and the homeostatic model assessment insulin resistance index(HOMA-IR)and other clinical data were detected at 8-12 weeks of pregnancy.Meanwhile,polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to detect the polymorphisms of ADIPOQ gene at S0100622 locus,IL-6 gene at S01006318 locus,TNF-αgene at S01009718.Receiver operating characteristics(ROC)curve was used to evaluate the diagnostic performance of FPG combined with polymorphisms of ADIPOQ,IL6 and TNF-α in predicting GDM in early pregnancy.Results The body mass index(BMI),early pregnancy FPG,mid pregnancy FPG,75 g oral glucose tolerance test(OGTT)1 h blood glucose,OGTT 2 h blood glucose,glycosylated hemoglobin(HbA1c),FINS and HOMA-IR in the GDM group were higher than those in the normal control group:(27.1±2.6)kg/m^(2) vs.(25.6±2.5)kg/m^(2),(4.7±1.3)mmol/L vs.(4.1±1.5)mmol/L,(5.5±1.3)mmol/L vs.(4.2±1.2)mmol/L,(6.3±1.5)mmol/L vs.(5.5±1.7)mmol/L,(6.0±1.5)mmol/L vs.(5.2±1.4)mmol/L,(5.8±0.7)%vs.(5.2±0.6)%,(6.4±1.1)mU/L vs.(5.2±1.2)mU/L,1.5±0.6 vs.1.0±0.7,there were statistical differences(P<0.05).According to the risk assessment of genotype,the high-risk rate in the GDM group was 88.33%(53/60),while the normal control group was 56.67%(34/60),there was statistical difference(χ^(2)=17.67,P<0.05).In GDM group,the HOMA-IR with ADIPOQ gene S0100622 locus TG genotype was higher than that with TT genotype:6.58±0.89 vs.4.98±0.58;the HOMA-IR with IL-6 gene S01006318 locus CG genotype was higher than CC and GG genotype:8.13±1.31 vs.6.53±0.81,4.85±0.54,the HOMA-IR with TNF-α gene S01009718 locus AG genotype was higher than GG genotype:6.31±1.04 vs.5.16±0.82,there were statistical differences(P<0.05).Logistic regression analysis showed that age>35 years,previous diabetes history,BMI,TG genotype at S0100622 locus of ADIPOQ gene,CG genotype at S01006318 locus of IL-6 gene,AG genotype at S01009718 locus TNF-α gene were risk factors for the onset of GDM(P<0.05).The results of ROC curve analysis showed that the area under the curve(AUC)of FPG for predicting GDM onset was 0.737,with a specificity of 83.50%;FPG combined with ADIPOQ,IL-6,TNF-α genetic risk assessment predicted with AUC of 0.921 and a specificity of 86.80%.Conclusions ADIPOQ gene TG genotype at S0100622 locus,IL-6 gene CG genotype at S01006318 locus,TNF-αgene AG genotype at the S01009718 locus has a certain correlation with the onset of GDM,which can predict the onset of GDM and is associated with perioperative insulin resistance in patients.Early FPG testing combined with genetic screening has practical clinical guiding significance in reducing adverse pregnancy outcomes for mothers and infants.