Glycated albumin in pregnancy: LC-MS/MS-based reference interval in healthy, nulliparous Scandinavian women and its diagnostic accuracy in gestational diabetes mellitus

Glycated albumin (GA) may be a useful biomarker of glycemia in pregnancy. The aim of this study was to establish the reference interval (RI) for GA, analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), in healthy, nulliparous pregnant women. In addition, we assessed the accuracy of GA and glycated hemoglobin A1c (HbA1c) in the diagnosis of gestational diabetes mellitus (GDM). Finally, we explored the prevalence of GDM in healthy nulliparas, comparing three diagnostic guidelines (WHO-1999, WHO-2013 and the Norwegian guideline). The study was carried out at Stavanger University Hospital, Norway, and included a study population of 147 pregnant nulliparous women. An oral glucose tolerance test (OGTT) was performed and used as the gold standard for GDM diagnosis. Blood samples for analysis of GA and HbA1c were collected at pregnancy week 24–28. A nonparametric approach was chosen for RI calculation, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of GA and HbA1c. The established RI for GA in 121 pregnant women was 7.1–11.6%. The area under the ROC curves (AUCs) were 0.531 (GA) and 0.627 (HbA1c). According to the WHO-1999, WHO-2013 and the Norwegian guideline, respectively, 24 (16%), 36 (24%) and 21 (14%) women were diagnosed with GDM. Only nine women (6%) fulfilled the GDM-criteria of all guidelines. In conclusion, we established the first LC-MS/MS-based RI for GA in pregnant women. At pregnancy weeks 24–28, neither GA nor HbA1c discriminated between those with and without GDM. Different women were diagnosed with GDM using the three guidelines.

糖化白蛋白（Glycated albumin, GA）或可成为妊娠期血糖水平的有效生物标志物。本研究旨在为采用液相色谱-串联质谱法（liquid chromatography-tandem mass spectrometry, LC-MS/MS）检测的GA，建立健康初产妇的参考区间（reference interval, RI）。此外，本研究评估了GA与糖化血红蛋白A1c（glycated hemoglobin A1c, HbA1c）在诊断妊娠期糖尿病（gestational diabetes mellitus, GDM）中的诊断准确度。最后，本研究探讨了健康初产妇群体中GDM的患病率，并对比了3种临床诊断指南：1999年世界卫生组织（WHO-1999）指南、2013年世界卫生组织（WHO-2013）指南以及挪威官方指南。
本研究于挪威斯塔万格大学医院开展，共纳入147名初产妇作为研究队列。所有受试者均接受口服葡萄糖耐量试验（oral glucose tolerance test, OGTT），并以此作为GDM诊断的金标准。研究人员于妊娠24~28周采集受试者静脉血样，用于GA与HbA1c的检测分析。
参考区间计算采用非参数统计方法，同时通过受试者工作特征（receiver operating characteristic, ROC）曲线评估GA与HbA1c的诊断效能。
本研究为121名产妇建立的GA参考区间为7.1%~11.6%。GA与HbA1c的ROC曲线下面积（AUCs）分别为0.531与0.627。按照WHO-1999、WHO-2013及挪威指南的诊断标准，分别有24名（16%）、36名（24%）与21名（14%）产妇被确诊为GDM。仅9名产妇（6%）同时满足所有3种指南的GDM诊断标准。
综上，本研究建立了首个基于LC-MS/MS检测方法的产妇GA参考区间。在妊娠24~28周这一孕周阶段，GA与HbA1c均无法有效区分GDM患者与非患病孕妇。采用3种不同指南进行诊断，得到的GDM患者人群存在显著差异。