Raczkowska Beata A, Mojsak Patrycja, Rojo David, Telejko Beata, Paczkowska-Abdulsalam Magdalena, Hryniewicka Justyna, Zielinska-Maciulewska Anna, Szelachowska Malgorzata, Gorska Maria, Barbas Coral, Kretowski Adam, Ciborowski Michal
Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Madrid, Spain.
Front Pharmacol. 2021 Nov 19;12:770240. doi: 10.3389/fphar.2021.770240. eCollection 2021.
Due to many adverse effects of gestational diabetes mellitus (GDM) on the mother and fetus, its diagnosis is crucial. The presence of GDM can be confirmed by an abnormal fasting plasma glucose level (aFPG) and/or oral glucose tolerance test (OGTT) performed mostly between 24 and 28 gestational week. Both aFPG and abnormal glucose tolerance (aGT) are used to diagnose GDM. In comparison to measurement of FPG, OGTT is time-consuming, usually inconvenient for the patient, and very often needs to be repeated. Therefore, it is necessary to seek tests that will be helpful and convenient to diagnose GDM. For this reason, we investigated the differences in fasting serum metabolites between GDM women with abnGM and normal FPG (aGT-GDM group), with aFPG and normal glucose metabolism (aFPG-GDM group) as well as pregnant women with normal glucose tolerance (NGT) being a control group. Serum metabolites were measured by an untargeted approach using gas chromatography-mass spectrometry (GC-MS). In the discovery phase, fasting serum samples collected from 79 pregnant women (aFPG-GDM, = 24; aGT-GDM, = 26; NGT, = 29) between 24 and 28 weeks of gestation (gwk) were fingerprinted. A set of metabolites (α-hydroxybutyric acid (α-HB), β-hydroxybutyric acid (β-HB), and several fatty acids) significant in aGT-GDM vs NGT but not significant in aFPG-GDM vs NGT comparison in the discovery phase was selected for validation. These metabolites were quantified by a targeted GC-MS method in a validation cohort consisted of 163 pregnant women (aFPG-GDM, = 51; aGT-GDM, = 44; and NGT, = 68). Targeted analyses were also performed on the serum collected from 92 healthy women in the first trimester (8-14 gwk) who were NGT at this time, but in the second trimester (24-28 gwk) they were diagnosed with GDM. It was found that α-HB, β-HB, and several fatty acids were associated with aGT-GDM. A combination of α-HB, β-HB, and myristic acid was found highly specific and sensitive for the diagnosis of GDM manifested by aGT-GDM (AUC = 0.828) or to select women at a risk of aGT-GDM in the first trimester (AUC = 0.791). Our findings provide new potential markers of GDM and may have implications for its early diagnosis.
由于妊娠期糖尿病（GDM）对母亲和胎儿有许多不良影响，其诊断至关重要。GDM的存在可通过空腹血糖水平异常（aFPG）和/或大多在孕24至28周进行的口服葡萄糖耐量试验（OGTT）来确诊。aFPG和葡萄糖耐量异常（aGT）均用于诊断GDM。与空腹血糖（FPG）测量相比，OGTT耗时，通常对患者不便，且常常需要重复进行。因此，有必要寻找有助于诊断GDM且方便的检测方法。出于这个原因，我们研究了异常葡萄糖耐量（abnGM）的GDM女性与空腹血糖正常（aGT - GDM组）、空腹血糖异常（aFPG）且葡萄糖代谢正常（aFPG - GDM组）的GDM女性以及葡萄糖耐量正常（NGT）的孕妇（作为对照组）之间空腹血清代谢物的差异。血清代谢物采用气相色谱 - 质谱联用（GC - MS）的非靶向方法进行测量。在发现阶段，对79名妊娠24至28周（gwk）的孕妇（aFPG - GDM组，n = 24；aGT - GDM组，n = 26；NGT组，n = 29）采集的空腹血清样本进行指纹图谱分析。在发现阶段，一组在aGT - GDM与NGT比较中有显著差异但在aFPG - GDM与NGT比较中无显著差异的代谢物（α - 羟基丁酸（α - HB）、β - 羟基丁酸（β - HB）和几种脂肪酸）被选作验证对象。这些代谢物通过靶向GC - MS方法在一个由163名孕妇组成的验证队列中进行定量分析（aFPG - GDM组，n = 51；aGT - GDM组，n = 44；NGT组，n = 68）。还对92名孕早期（8 - 14 gwk）时葡萄糖耐量正常（NGT）但孕中期（24 - 28 gwk）被诊断为GDM的健康女性的血清进行了靶向分析。结果发现，α - HB、β - HB和几种脂肪酸与aGT - GDM相关。发现α - HB、β - HB和肉豆蔻酸的组合对以aGT - GDM表现的GDM诊断具有高度特异性和敏感性（曲线下面积（AUC）= 0.828），或者在孕早期筛选有aGT - GDM风险的女性时具有较高的AUC（0.791）。我们的研究结果为GDM提供了新的潜在标志物，可能对其早期诊断有重要意义。
