Kopylov Arthur T, Kaysheva Anna L, Papysheva Olga, Gribova Iveta, Kotaysch Galina, Kharitonova Lubov, Mayatskaya Tatiana, Krasheninnikova Anna, Morozov Sergey G
Department of Pathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia.
Department of Proteomic Researches, Institute of Biomedical Chemistry, 119121 Moscow, Russia.
Cells. 2020 Apr 21;9(4):1032. doi: 10.3390/cells9041032.
The purpose of the study is to establish and quantitatively assess protein markers and their combination in association with insulin uptake that may be have value for early prospective recognition of diabetic fetopathy (DF) as a complication in patients with diabetes mellitus during gestation.
Proteomic surveying and accurate quantitative measurement of selected proteins from plasma samples collected from the patients with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) who gave birth of either healthy or affected by maternal diabetes newborns was performed using mass spectrometry.
We determined and quantitatively measured several proteins, including CRP, CEACAM1, CNDP1 and Ig-family that were significantly differed in patients that gave birth of newborns with signs of DF. We found that patients with newborns associated with DF are characterized by significantly decreased CEACAM1 (113.18 ± 16.23 ng/mL and 81.09 ± 10.54 ng/mL in GDM and T2DM, < 0.005) in contrast to control group (515.6 ± 72.14 ng/mL, < 0.005). On the contrary, the concentration of CNDP1 was increased in DF-associated groups and attained 49.3 ± 5.18 ng/mL and 37.7 ± 3.34 ng/mL ( < 0.005) in GDM and T2DM groups, respectively. Among other proteins, dramatically decreased concentration of IgG4 and IgA2 subclasses of immunoglobulins were noticed.
The combination of the measured markers may assist (AUC = 0.893 (CI 95%, 0.785-0.980) in establishing the clinical finding of the developing DF especially in patients with GDM who are at the highest risk of chronic insulin resistance.
本研究的目的是建立并定量评估与胰岛素摄取相关的蛋白质标志物及其组合,这些标志物可能对早期前瞻性识别糖尿病胎儿病(DF)有价值,DF是妊娠期糖尿病患者的一种并发症。
采用质谱法对患有妊娠期糖尿病(GDM)和2型糖尿病(T2DM)且分娩出健康或受母体糖尿病影响新生儿的患者血浆样本中的选定蛋白质进行蛋白质组学检测和精确定量测量。
我们测定并定量测量了几种蛋白质,包括CRP、CEACAM1、CNDP1和免疫球蛋白家族,这些蛋白质在分娩出有DF迹象新生儿的患者中存在显著差异。我们发现,与DF相关的新生儿患者的特征是CEACAM1显著降低(GDM组和T2DM组分别为113.18±16.23 ng/mL和81.09±10.54 ng/mL,<0.005),而对照组为515.6±72.14 ng/mL(<0.005)。相反,CNDP1的浓度在与DF相关的组中升高,GDM组和T2DM组分别达到49.3±5.18 ng/mL和37.7±3.34 ng/mL(<0.005)。在其他蛋白质中,免疫球蛋白的IgG4和IgA2亚类浓度显著降低。
所测标志物的组合可能有助于(AUC=0.893(95%CI,0.785 - 0.980))确立DF发展的临床发现,尤其是在慢性胰岛素抵抗风险最高的GDM患者中。