妊娠早期血清25-羟基维生素D3与妊娠期糖尿病的相关研究

Relationship between first-trimester serum level of 25-hydroxyvitamin D3 and gestational diabetes mellitus

目的：探讨妊娠早期血清25-羟基维生素D3（25[OH]D3）水平与妊娠期糖尿病（GDM）发病的相关性。方法选取2011年6月到2013年3月在广东省妇幼保健院产科产检并住院分娩的孕妇1768名作为研究对象，所有研究对象均于妊娠6-13周登记入组，入组时检测糖脂代谢指标和血清25[OH]D3水平，妊娠24-28周进行75 g口服葡萄糖耐量试验（OGTT）；根据妊娠早期空腹血糖（FBG）及OGTT结果，分为GDM组[n=350，年龄（29±5）岁]和正常孕妇组[n=1418，年龄（29±4）岁]，比较两组间妊娠早期血清25[OH]D3水平和糖脂代谢指标；统计分析采用t检验、Pearson相关分析、logistic回归分析。结果 GDM组孕妇孕前体质指数（BMI）明显高于正常孕妇组（t=5.913，P〈0.05）；两组年龄差异无统计学意义（t=0.342，P〉0.05）；GDM组妊娠早期血清25[OH]D3水平明显低于正常孕妇组（t=17.936，P〈0.05）；Pearson相关分析显示血清25[OH]D3水平与稳态模型胰岛素抵抗指数（HOMA-IR）、TG、孕前BMI呈负相关（r=－0.867、－0.133、－0.244，均P〈0.05）；Logistic回归分析显示血清25[OH]D3水平与GDM发病相关，校正孕前BMI、TG、LDL-C、FBG和HOMA-IR的影响因素后，血清25[OH]D3水平仍与GDM发病相关，是GDM独立危险因素，其缺乏的孕妇发生GDM的风险是不缺乏者的1.669倍（比值比1.669，95%可信区间：1.460-1.912，P〈0.05）；受试者工作曲线（ROC）显示，妊娠早期血清25[OH]D3小于28.2 nmol/L时，预测GDM发病的灵敏度为85.9%，特异度为83.7%。结论 GDM孕妇妊娠早期血清25[OH]D3水平明显降低，妊娠早期维生素D缺乏与GDM发病相关；血清25[OH]D3水平可能与妊娠早期糖脂代谢异常有关；妊娠早期25[OH]D3水平小于28.2 nmol/L对GDM发病具有预测意义。

Objective To explore the relationship between serum level of 25-hydroxyvitamin D3 （25-[OH]D3）at first trimester of pregnancy and gestational diabetes mellitus（GDM）. Methods The prospective case-control study involved 1 768 women who took antenatal care at Guangdong Women and Children Hospital from June 2011 to March 2013. All subjects were enroled at 6-13 weeks of gestation and blood sample was taken to measure glucolipid metabolic index and 25-[OH]D3 levels. At 24-28 weeks of gestation,all subjects took 75 g oral glucose tolerance test（OGTT）. The subjects were divided into GDM group（n=350,maternal age（29±5）years）and control group（n=1 418,maternal age（29±4）years）according to results of OGTT and fasting blood glucose（FBG）,and then 25-[OH] D3 levels and glucolipid metabolic index between the two groups were compared. Data was analyzed by using independent t test,Pearson correlation,logistic regression. Results The progestational body mass index（BMI）of GDM patients was significantly higher（（22.6 ± 3.1 vs 20.5 ± 2.1）kg/m^2,t=5.913,P〈0.05）as compared with the controls.There was no significant difference of maternal age between the two groups（t=0.342,P〉0.05）.Among women who developed GDM,maternal serum 25-[OH] D3 concentrations at first trimester of pregnancy were significantly lower than the controls（（23.8 ± 3.3 vs 37.8 ± 12.8）nmol/L,t=17.936,P〈0.05）;The serum 25-[OH] D3 levels were significantly and negatively correlated with HOMA-IR（r=-0.867,P〈0.05）,TG（r=-0.133,P〈0.05）, progestational BMI（r=-0.244,P〈0.05）;Women who were classified as being deficient for vitamin D had a 1.669-fold increased subsequent risk of GDM,as compared with vitamin D sufficient women after adjustment for progestational BMI,TG,LDL-C,FBG,HOMA-IR（adjusted OR：1.669;95%CI：1.460-1.912, P〈0.05）;The receiver operating characteristic curve（ROC）analysis showed that the sensitivity was 85.9%and the specificity was 83.7%in predicting GDM at point of 28.2 nmol/L of serum 25-[OH] D3 concentration. Conclusions The serum 25-[OH] D3 concentrations at first trimester of pregnancy were significantly decreased in women who were subsequently developed GDM. Maternal vitamin D deficiency at first trimester of pregnancy is associated with an elevated risk for GDM.