Supplementary Material for: A Prospective Study of Maternal Plasma Concentrations of Retinol-Binding Protein 4 and Risk of Gestational Diabetes Mellitus

<b><i>Background:</i></b> The aim of this study was to investigate whether retinol-binding protein 4 (RBP4) concentrations, measured at the first prenatal visit, are associated with risk of gestational diabetes mellitus (GDM). <b><i>Methods:</i></b> From July 2015 to June 2016, consecutive women who admitted to the obstetrics center of our hospital were included. At the first prenatal visit (the median gestational age was 6 [interquartile range 4–10] weeks) in the hospital, involved subjects were tested for fasting plasma glucose (FPG) and RBP4 using venous plasma samples collected after at least 8 h of fasting in the morning. Data for FPG and RBP4 concentrations at the first prenatal visit and one-step GDM screening with 75-g oral glucose tolerance test performed between 24 and 28 weeks of gestation were collected and analyzed. <b><i>Results:</i></b> Blood at first prenatal visit was available for 827 women, among whom GDM developed in 101 (12.2%). In multivariate models comparing the second (Q2), third, and fourth quartiles against the first quartile of RBP4, concentrations of RBP4 in Q2, Q3, and Q4 were associated with GDM later developed, and increased risk of GDM by 54, 205, and 536%. There was a significant statistical difference in the area under the curve between the established risk factors alone and the addition of RBP4 concentrations (difference, 0.039 [95% CI 0.030–0.052]; <i>p</i> = 0.03). In the subgroup of women combined with obesity and FABP4 ≥median, the measured OR was 9.83 (95% CI [4.76–16.13]; <i>p</i> &lt; 0.001) for GDM compared to those without obesity and FABP4 <i>Conclusions:</i> There is evidence of a positive association of early pregnancy elevated RBP4 concentration with increased GDM risk, particularly among women with advanced age and obesity.

<b><i>研究背景：</i></b> 本研究旨在探讨首次产前检查时检测的视黄醇结合蛋白4（retinol-binding protein 4, RBP4）浓度是否与妊娠期糖尿病（gestational diabetes mellitus, GDM）的发病风险相关。<b><i>研究方法：</i></b> 2015年7月至2016年6月，本院产科中心连续就诊的孕妇被纳入本研究。受试者于首次产前检查时（中位孕周为6[四分位间距4~10]周），采集清晨空腹至少8小时后的静脉血浆样本，检测空腹血浆葡萄糖（fasting plasma glucose, FPG）与RBP4浓度。本研究收集并分析了受试者首次产前检查时的FPG、RBP4浓度数据，以及妊娠24~28周时实施的75g口服葡萄糖耐量试验（oral glucose tolerance test, OGTT）一步法GDM筛查结果。<b><i>研究结果：</i></b> 本研究共获取827名孕妇首次产前检查时的血液样本，其中101名（12.2%）后续发生了GDM。以RBP4第一四分位数组为参照，多因素模型分析显示，第二（Q2）、第三、第四四分位数组的RBP4浓度均与后续GDM发病相关，对应的GDM发病风险分别升高54%、205%及536%。仅纳入既定危险因素的模型与额外加入RBP4浓度的模型相比，曲线下面积存在显著统计学差异（差值为0.039[95%置信区间（confidence interval, CI）0.030~0.052]；p=0.03）。在合并肥胖且脂肪酸结合蛋白4（fatty acid-binding protein 4, FABP4）≥中位数的孕妇亚组中，与无肥胖且FABP4低于中位数的孕妇相比，其发生GDM的比值比（odds ratio, OR）为9.83（95%CI[4.76~16.13]；p<0.001）。<b><i>研究结论：</i></b> 现有证据表明，妊娠早期RBP4浓度升高与GDM发病风险升高呈正相关，尤其在高龄及肥胖孕妇群体中更为显著。