血清Apelin对中晚期孕妇发生妊娠期糖尿病的影响及其水平变化研究

Serum Apelin Level and Its Influence on Gestational Diabetes in Advanced Stages of Pregnancy

背景妊娠期糖尿病(GDM)是一种常见的妊娠期并发症之一,新型脂肪因子Apelin为APJ受体内源性配体,研究发现Apelin与胰岛素抵抗密切相关,参与体内糖代谢过程。目的了解中晚期孕妇血清Apelin水平变化并分析Apelin对GDM糖脂代谢的影响。方法选择2018年10月-2019年5月于安徽医科大学第一附属医院内分泌科行75 g口服葡萄糖耐量试验(OGTT)的妊娠24~32周的妊娠期女性196例,根据OGTT结果分为糖代谢异常组(GDM组,n=98)与糖代谢正常组(NGT组,n=98)。再根据低密度脂蛋白胆固醇(LDL-C)水平将GDM组分为LDL-C正常亚组(GDM-NL亚组,n=49)和LDL-C升高亚组(GDM-HL亚组,n=49);同样将NGT组分为LDL-C正常亚组(NGT-NL亚组,n=44)及LDL-C升高亚组(NGT-HL亚组,n=54)。记录研究对象一般人口学特征,测定空腹血糖(FBG)、1 h血糖(1 hBG)、2 h血糖(2 hBG)、空腹胰岛素(FINS)、1 h胰岛素(1 hINS)、2 h胰岛素(2 hINS)、空腹C肽(FCP)、1 hC肽(1 hCP)、2 hC肽(2 hCP)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、LDL-C。计算胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、胰岛素敏感指数(ISI)、矫正胰岛β细胞功能指数(MBCI)、血糖曲线下面积(AUC-G)、胰岛素曲线下面积(AUC-I)。采用酶联免疫吸附法测定空腹血清Apelin水平。结果GDM组FBG、1 hBG、2 hBG、FINS、1 hINS、2 hINS、FCP、2 hCP、HOMA-IR、AUC-G、AUC-I高于NGT组,HOMA-β、ISI低于NGT组(P<0.05)。GDM组血清Apelin水平低于NGT组(P<0.001)。GDM-NL亚组、GDM-HL亚组血清Apelin水平均低于NGT-NL亚组、NGT-HL亚组(P<0.05)。Pearson相关分析显示,血清Apelin与妊娠前BMI、FBG、1 hBG、2 hBG、FINS、2 hINS、FCP、1 hCP、2 hCP、HOMA-IR、AUC-G、AUC-I呈负相关,与ISI呈正相关(P<0.05)。多因素Logistic回归分析结果显示,Apelin是妊娠中晚期孕妇发生GDM的影响因素〔OR=0.977,95%CI(0.964,0.990),P<0.001〕。结论妊娠中晚期孕妇Apelin水平与胰岛素抵抗呈负相关,GDM患者血清Apelin水平显著减低,且Apelin是妊娠中晚期孕妇发生GDM的影响因素,提示Apelin可能参与GDM的糖代谢过程。

Background Gestational diabetes mellitus(GDM)is one of the most common complications in pregnancy.Studies have found that a novel fat factor Apelin,the endogenous ligand of APJ receptor,is closely related to insulin resistance and participates in the process of glucose metabolism in vivo.Objective To investigate the serum Apelin level and its possible role in glycolipid metabolism in GDM patients.Methods From Department of Endocrinology,the First Affiliated Hospital of Anhui Medical University,196 pregnant women at 24-32 weeks of gestation were enrolled from October 2018 to May 2019.Data were recorded,including general demographic information,glycemic parameters measured by the 2-hour 75-gram oral glucose tolerance test(OGTT)〔fasting blood glucose(FBG),1-hour postprandial glucose(1 hBG),2-hour postprandial glucose(2 hBG)〕,insulin response parameters measured by the 2-hour insulin response test(IRT)〔fasting insulin(FINS),1-hour postprandial insulin(1 hINS),2-hour postprandial insulin(2 hINS)〕,and parameters of C-peptide〔fasting C-peptide(FCP),1-hour postprandial C-peptide(1 hCP),2-hour postprandial C-peptide(2 hCP)〕,serum lipid parameters(TC,TG,HDL-C and LDL-C),and calculated HOMA-IR,homeostasis model assessment ofβ-cell function(HOMA-β),insulin sensitivity index(ISI)modified beta-cell function index(MBCI),glucose AUC(AUC-G),insulin AUC(AUC-I),and ELISA-detected fasting serum Apelin.The Apelin level and glycolipid metabolism parameters were analyzed between those with normal and abnormal glucose metabolism(NGT and GDM groups,98 cases respectively)stratified by OGTT results,and were further analyzed between those with normal and higher LDL-C in NGT group(NGT-NL and NGT-HL subgroups,44 cases and 54 cases respectively)and in GDM group(GDM-NL and GDM-HL subgroups,49 cases respectively),respectively.Results Compared with NGT group,GDM group showed higher average levels of FBG,1 hBG,2 hBG,FINS,1 hINS,2 hINS,FCP,2 hCP,HOMA-IR,AUC-G,and AUC-I,but lower average HOMA-βand ISI(P<0.05).They also showed significantly lower average serum Apelin level(P<0.001).GDM patients with normal LDL-C had lower average level of serum Apelin than NGT patients with normal or higher LDL-C(P<0.05),so did GDM patients with higher LDL-C(P<0.05).Pearson correlation analysis showed that serum Apelin was negatively correlated with pre-pregnancy BMI,FBG,1 hBG,2 hBG,FINS,2 hINS,FCP,1 hCP,2 hCP,HOMA-IR,AUC-G,and AUC-I(P<0.05),but was positively correlated with ISI(P<0.05).Multivariate Logistic regression analysis showed that Apelin was the influencing factor of GDM〔OR=0.977,95%CI(0.964,0.990),P<0.001〕.Conclusion Apelin level is negatively correlated with insulin resistance in advanced stages of pregnancy.The serum Apelin level in GDM patients is significantly reduced,and Apelin is the influencing factor of GDM in advanced stages of pregnancy.Apelin may be involved in the glucose metabolism of GDM.