瘦素与妊娠糖尿病患者胰岛素抵抗及胎儿发育的相关性

目的 探讨瘦素及可溶性瘦素受体(sLR)在妊娠糖尿病发病及胎儿发育中的作用.方法 选取2014年1月至12月在厦门大学附属成功医院连续产检并分娩的673名孕妇为研究对象,跟踪随访至孕晚期.根据糖耐量试验结果,采用随机抽样法选取50例血糖控制良好的妊娠糖尿病患者纳入妊娠糖尿病组,根据一般资料进行匹配选取50名糖耐量试验结果阴性者纳入正常妊娠组.根据妊娠周数分为孕早期和孕晚期亚组,比较两组不同孕期血清及脐血瘦素、sLR、脂联素、抵抗素及生化指标水平,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR),精确测量新生儿生长发育指标,使用多元Logistic回归分析孕早期胰岛素抵抗的危险因素,同时采用Spearman相关性分析血清瘦素与sLR、脂联素、抵抗素及生化指标水平的相关性.结果 与正常妊娠组相比,妊娠糖尿病组孕早期血清瘦素、甘油三酯、总胆固醇、低密度脂蛋白-胆固醇(LDL-C)、空腹胰岛素(FINS)、HOMA-IR明显升高(t=0.938～6.864,P均＜0.05),sLR、脂联素显著降低(t=9.237、2.216,P均＜0.05),抵抗素、高密度脂蛋白-胆固醇(HDL-C)、空腹血糖差异无统计学意义(P均＞0.05).与正常妊娠组相比,妊娠糖尿病组孕晚期血清瘦素、抵抗素、空腹血糖、FINS、甘油三酯、总胆固醇、LDL-C、HOMA-IR明显升高(t=0.429 ～ 13.787,P均＜0.05),sLR、脂联素显著降低(t=2.216、5.623,P均＜0.05),HDL-C差异无统计学意义(P＞0.05).与正常妊娠组相比,妊娠糖尿病组脐血瘦素、抵抗素明显升高(t=1.007、11.857,P均＜0.05),sLR、脂联素显著降低(t=0.201、4.558,P均＜0.05).多元Logistic回归分析显示,瘦素(OR =1.288,95％ CI:1.137 ～4.370)、抵抗素(OR=1.223,95％CI:1.035～ 1.570)、总胆固醇(OR=1.216,95％CI:1.026 ～1.823)、甘油三酯(OR=1.357,95％CI:1.008～ 3.572)、LDL-C (OR=1.634,95％ CI:1.251～3.764)是妊娠糖尿病组孕早期发生胰岛素抵抗的独立危险因素,sLR (OR =0.714,95％ CI:0.161～0.893)、脂联素(OR =0.352,95％CI:0.112 ～0.510)是妊娠糖尿病组孕早期发生胰岛素抵抗的保护性因素.妊娠糖尿病组孕晚期母体血瘦素含量与sLR、脂联素均呈负相关(r=-0.16、-1.13,P均=0.000),与抵抗素呈正相关(r=0.269,P=0.019).妊娠糖尿病组脐血瘦素含量与sLR、脂联素均呈负相关(r=-0.147、-1.250,P均=0.000),与抵抗素、体重、Ponderal 指数均呈正相关(r =0.410、0.673、0.301,P均＜0.05),与头围、身长无关(P均＞0.05).结论 瘦素及sLR与妊娠糖尿病患者胰岛素抵抗存在相关性,但与胎儿宫内生长和发育无关.

Relationship between leptin and insulin resistance,fetal growth and development in patients with gestational diabetes mellitus

Objective To investigate the effect of leptin and soluble leptin receptor (sLR) on the occurrence of gestational diabetes mellitus(GDM) and fetal growth and development.Methods A total of 673 pregnant women with continuous prenatal care visits and gave birth at the Chenggong Affiliated Hospital of Xiamen University from January to December in 2014 were selected,and followed up until late pregnancy.Based on the results of glucose tolerance test,50 GDM patients with well-controlled glucose levels were selected into the GDM group by random sampling method.Another 50 pregnant women with similar demographic features and normal glucose tolerance results were enrolled into the normal pregnancy group.Based on gestational age,the two groups were further divided into early pregnancy and late pregnancy groups.Serum leptin and umbilical blood leptin,sLR,adiponectin,resistin and other biochemical indexes were measured;homeostasis model of assessment for insulin resistance index (HOMA-IR) was calculated;and neonatal anthropometry was also measured.Multiple Logistic regression method was used to analyze the risk factors of insulin resistance in early pregnancy.Spearman correlation analysis was applied in analyzing the correlation between serum leptin levels and sLR,adiponectin,resistin,biochemical indicators.Results In early pregnancy,compared with normal pregnancy group,serum leptin,fasting insulin (FINS),total cholesterol,triglyceride,low density lipoprotein-cholesterol (LDL-C) were increased (t =0.938-6.864,all P ＜ 0.05),while the levels of sLR and adiponectin were decreased in GDM group (t =9.237,2.216,all P ＜ 0.05).No statistical significance was found in resistin,high density lipoprotein-cholesterol (HDL-C) and fasting glucose levels(all P ＞0.05).In late pregnancy,compared with normal pregnancy group,the levels of serum leptin,resistin,fasting glucose,FINS,triglyceride,total cholesterol,LDL-C and HOMA-IR were increased(t =0.429-13.787,all P ＜ 0.05),while the levels of sLR and adiponectin were decreased in GDM group (t =2.216,5.623,all P ＜ 0.05).There was no statistical difference in HDL-C level (P ＞ 0.05).Compared with normal pregnancy group,the levels of umbilical blood leptin and resistin were increased (t =1.007,11.857,all P ＜ 0.05),while the levels of sLR and adiponectin were decreased in GDM group (t =1.007,11.857,all P ＜ 0.05).Multiple Logistic regression analysis showed that,in early pregnancy,leptin(OR =1.288,95％ CI:1.137-4.370),resistin(OR =1.223,95％ CI:1.035-1.570),total cholesterol(OR =1.216,95％ CI:1.026-1.823),triglyceride (OR =1.357,95％ CI:1.008-3.572) and LDL-C (OR =1.634,95％ CI:1.251-3.764) were independent risk factors for the occurrence of insulin resistance in GDM group.sLR(OR=0.714,95％CI:0.161-0.893) and adiponectin(OR=0.352,95％CI:0.112-0.510)were protective factors of GDM group in early pregnancy.For patients of late pregnancy in GDM group,the level of maternal blood leptin was negatively correlated with sLR and adiponectin (r =-0.16,-1.13,all P =0.000),while positively correlated to resistin (r =0.269,P =0.019).The level of umbilical blood leptin of GDM group showed negative correlation with sLR and adiponectin (r =-0.147,-1.250,all P =0.000),positive correlation with resistin,body weight,Ponderal index (r =0.410,0.673,0.301,all P ＜ 0.05).Conclusion Leptin and sLR are correlated with insulin resistance in patients with GDM,but not with fetal growth and development.