妊娠期高血糖孕妇血糖控制水平对胎盘葡萄糖转运蛋白的影响

Effects of glycemic control on placental glucose transporters in women with hyperglycemia in pregnancy

目的探讨孕期高血糖孕妇胎盘葡萄糖转运蛋白(glucose transport protein,GLUT)1及4的表达变化以及孕妇血糖控制水平对其的影响。方法回顾性纳入2017年1月至2019年12月于北京大学第一医院行择期剖宫产的足月、单胎妊娠孕妇,其中孕前糖尿病(pregestational diabetes mellitus,PGDM)孕妇16例为PGDM组,妊娠期糖尿病(gestational diabetes mellitus,GDM)孕妇16例为GDM组,无血糖异常的孕妇16例为正常糖耐量(normal glucose tolerance,NGT)组。PGDM组和GDM组进一步根据孕期血糖控制水平是否良好分为PGDM-控制良好亚组(n=10)、PGDM-控制不良亚组(n=6)、GDM-控制良好亚组(n=10)和GDM-控制不良亚组(n=6)。采用蛋白质印迹技术检测各组孕妇胎盘中GLUT1和GLUT4的表达水平。比较组间GLUT1和GLUT4的表达水平,分析GLUT1和GLUT4表达水平与孕前体重指数、分娩前体重、孕期增重、新生儿出生体重的相关性。采用两独立样本t检验、单因素方差分析(两两比较采用LSD检验)、Kruskal-Wallis H检验、χ^(2)检验、Pearson相关分析进行统计学分析。结果(1)PGDM组孕妇孕前体重指数和胰岛素治疗比例高于GDM组及NGT组[27.0 kg/m^(2)(22.1~29.9 kg/m^(2))与22.9 kg/m^(2)(20.5~25.7 kg/m^(2))和21.7 kg/m^(2)(20.5~24.3 kg/m^(2));13/16与1/16和0/16],PGDM组孕妇中孕期空腹血糖、中孕期和晚孕期平均糖化血红蛋白高于GDM组[(6.1±1.2)与(5.0±0.4)mmol/L;(5.9±0.5)%与(5.2±0.3)%],P值均<0.05。(2)GLUT1水平在PGDM组及GDM组高于NGT组(1.251±0.354、1.004±0.368与0.733±0.216),在PGDM组高于GDM组;在PGDM-控制良好亚组(1.270±0.417)及PGDM-控制不良亚组(1.218±0.245)、GDM-控制良好亚组(0.900±0.424)及GDM-控制不良亚组(1.177±0.158)也均高于NGT组(LSD检验,P值均<0.05)。GLUT4水平变化趋势与GLUT1一致。PGDM-控制不良亚组与PGDM-控制良好亚组比较,GDM-控制不良亚组与GDM-控制良好亚组比较,GLUT1和GLUT4表达水平差异均无统计学意义(P值均>0.05)。(3)PGDM-控制良好亚组GLUT1、GLUT4及GDM-控制不良亚组的GLUT1与孕期增重正相关(r值分別为0.635、0.810和0.833,P值均<0.05)。结论不同类型孕期高血糖及孕期增重与胎盘GLUT1和GLUT4表达水平有关,但血糖控制水平对胎盘GLUT的表达水平影响较小。

Objective To investigate the expression of placental glucose transport protein(GLUT)1 and 4 in women with hyperglycemia in pregnancy.Methods A total of 48 full-term singleton pregnant women who underwent elective cesarean section at Peking University First Hospital from January 2017 to December 2019 were included retrospectively,and were divided into pregestational diabetes mellitus(PGDM)group,gestational diabetes mellitus(GDM)group,and normal glucose tolerance(NGT)group(16 women in each).According to the blood glucose level after control during pregnancy,the PGDM and GDM groups were further divided into PGDM-,GDM-well controlled subgroups(both n=10),and PGDM-,GDM-uncontrolled subgroups(both n=6).The expression of GLUT1 and GLUT4 proteins,detected by Western blot,between different groups were compared and the correlation between GLUT1 and GLUT4 protein expression and the pre-pregnancy body mass index(BMI),pre-delivery weight,gestational weight gain(GWG),and neonatal birth weight were analyzed using two independent samples t-test,one-way analysis of variance,Kruskal-Wallis H-test,Chi-square test,and Pearson correlation analysis.Results(1)The pre-pregnanct BMI and insulin treatment ratio in PGDM group were higher than those in GDM group and NGT group[27.0 kg/m^(2)(22.1-29.9 kg/m^(2))vs 22.9 kg/m^(2)(20.5-25.7 kg/m^(2))and 21.7 kg/m^(2)(20.5-24.3 kg/m^(2));13/16 vs 1/16 and 0/16;all P<0.05].In the PGDM group,fasting blood glucose at the second trimester and mean glycosylated hemoglobin during the second and the third trimester were higher than those in the GDM group[(6.1±1.2)vs(5.0±0.4)mmol/L;(5.9±0.5)%vs(5.2±0.3)%;both P<0.05].(2)GLUT1 protein level was the highest in the PGDM group,followed by the GDM and NGT group(1.251±0.354 vs 1.004±0.368 vs 0.733±0.216,both P<0.05).And all the subgroups had higher protein level than NGT group[PGDM-good(1.270±0.417);PGDM-uncontrolled(1.218±0.245),GDM-well controlled(0.900±0.424);GDM-uncontrolled(1.177±0.158);LSD test,all P<0.05].The variation of GLUT4 protein level was consistent with GLUT1.There was no significant difference in GLUT1 and GLUT4 expression between PGDM-uncontrolled and PGDM-well controlled subgroups,neither between GDM-uncontrolled and GDM-well controlled subgroups(all P>0.05).(3)GLUT1 and GLUT4 in the PGDM-well controlled subgroup,as well as GLUT1 in the GDM-uncontrolled subgroup,had a positive correlation with GWG(r=0.635,0.810,and 0.833,all P<0.05).Conclusions The increased expression of placental GLUT1 and GLUT4 were associated with different types of gestational hyperglycemia and GWG.However,glucose control has little effect on placental GLUT expression.