孕中期血浆n-6多不饱和脂肪酸水平与妊娠期糖尿病的关联

Association of plasma n-6 polyunsaturated fatty acids with gestational diabetes mellitus in the second trimester

目的探讨中国西南地区孕妇孕中期血浆n-6多不饱和脂肪酸(polyunsaturated fatty acids,PUFAs)水平与妊娠期糖尿病(gestational diabetes mellitus,GDM)的关联。方法本研究基于同济-双流出生队列,于2017―2019年在成都市双流区妇幼保健院围产保健门诊纳入18~40岁的6143名单胎妊娠孕妇。通过问卷调查收集孕妇基本信息和孕期健康状况,并对其进行体格测量和血液样本收集。根据孕24~28周孕妇75 g口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)结果,选取269名符合GDM诊断标准的孕妇作为病例组。在非GDM的孕妇中按照孕妇年龄(±3岁)、基线孕周(±4周)进行1∶2匹配,选取538名非GDM孕妇作为对照组。采用气相色谱-质谱联用的方法检测孕妇孕中期血浆多种n-6 PUFAs水平。采用多变量校正的条件Logistic回归分析模型评估孕中期血浆各n-6 PUFAs类别和总n-6 PUFAs与GDM患病风险的关联,并利用错误发现率(false discovery rate,FDR)法校正多重检验。采用敏感性分析探讨其稳健性。结果807名研究对象的年龄为(27.8±3.9)岁,孕周为(24.8±1.1)周,孕前BMI为(21.5±3.1)kg/m^(2)。孕中期血浆亚油酸(linoleic acid,LA)、γ-亚油酸(gamma-linolenic acid,GLA)、二十碳二烯酸(eicosadienoic acid,EDA)和花生四烯酸(arachidonic acid,AA)水平每增加一个标准差,GDM的患病风险的OR值分别为0.83(95%CI:0.69~0.99,P=0.039)、0.82(95%CI:0.69~0.99,P=0.037)、0.63(95%CI:0.50~0.79,P<0.001)和1.20(95%CI:1.02~1.42,P=0.032),而多重校正后LA、GLA和AA与GDM患病风险关联无统计学意义(均有P>0.05)。敏感性分析结果显示EDA与GDM患病风险的关联稳定。结论孕中期血浆n-6 PUFAs中EDA与GDM患病风险有关,此结论需进一步在大样本人群中进行验证。

Objective The study aims to explore the association of plasma n-6 polyunsaturated fatty acids(PUFAs)with gestational diabetes mellitus(GDM)in the second trimester of pregnant women in southwest China.Methods In the Tongji-Shuangliu Birth Cohort,6143 women with a singleton pregnancy(aged 18-40 years)were enrolled at the clinics of perinatal care in the Shuangliu Maternal and Child Health Care Hospital in Chengdu from 2017 to 2019.Basic information of participants was collected by questionnaire and physical examinations were performed at enrollment,and blood samples were collected in the second trimester.A total of 269 pregnant women were diagnosed as having GDM based on the 75 g oral glucose tolerance test during 24-28 weeks.The GDM cases were matched individually to 538 non-GDM controls at a 1∶2 ratio on maternal age(±3 years)and baseline gestational week(±4 weeks).Plasma n-6 PUFAs were determined by gas chromatography-mass spectrometry in the second trimester.The associations of individual n-6 PUFAs and total n-6 PUFAs with GDM were evaluated using multivariable conditional Logistic regression models,and false discovery rate(FDR)was used for the correction of multiple comparison.Sensitivity analysis was used to test the robustness of the associations.Results Of the 807 participants,maternal age was(27.8±3.9)years,and gestational age was(24.8±1.1)weeks,and pre-pregnancy BMI was(21.5±3.1)kg/m^(2).Odds ratios(ORs)for GDM in relation to each 1-SD increase in plasma linoleic acid(LA),gamma-linolenic acid(GLA),eicosadienoic acid(EDA),and arachidonic acid(AA)were 0.83(95%CI:0.69-0.99,P=0.039),0.82(95%CI:0.69-0.99,P=0.037),0.63(95%CI:0.50-0.79,P<0.001)and 1.20(95%CI:1.02-1.42,P=0.032),respectively;however,the associations of LA,GLA,and AA with GDM became not significant after FDR correction(all P>0.05).The association of EDA with GDM were robust in sensitivity analyses.Conclusion Plasma EDA in the second trimester was associated with GDM,which needs to be further validated in other populations.