盐酸二甲双胍联合门冬胰岛素治疗对妊娠糖尿病孕妇生产结局的影响

Effect of metformin hydrochloride combined with insulin aspart on the outcome of pregnant women with gestational diabetes mellitus

目的观察盐酸二甲双胍联合门冬胰岛素治疗对妊娠糖尿病(GDM)患者胰岛素抵抗和生产结局的影响。方法选取2016年7月至2019年2月日照市中医医院诊治的106例GDM患者作为研究对象。采用随机数字表法将其随机分为观察组(n=53)和对照组(n=53)。两组患者均给予门冬胰岛素皮下注射治疗,观察组同时给予盐酸二甲双胍。比较两组患者治疗前和治疗1个月后空腹血糖(FPG)、空腹胰岛素(FINS),比较治疗1个月后胰岛素抵抗程度[稳态模式胰岛素抵抗指数(HOMA-IR)、稳态模式胰岛素分泌指数(HOMA-β)、胰岛素混合敏感指数(ISIcomp)]、脐血流阻力参数[搏动指数(PI)、阻力指数(RI)、收缩期最大血流速度(S)/舒张末期血流速度峰值(D)]、血清一氧化氮(NO)水平和血清内皮素-1(ET-1)水平,比较治疗前后两组患者的血清RBP4、Apelin水平;记录并比较两组患者妊娠情况及新生儿情况。结果治疗后观察组患者的FPG和FINS分别为(4.57±1.02)mmol/L和(14.39±2.31)mIU/L,低于治疗前,且低于对照组患者的(5.26±1.14)mmol/L和(17.65±2.23)mIU/L,差异均具有统计学意义(均P<0.05);治疗1个月后观察组患者的HOMA-IR、HOMA-β均低于对照组患者,而ISIcomp则高于对照组,差异均具有统计学意义(均P<0.05);观察组患者治疗后脐动脉超声参数均低于对照组患者,其血清NO水平高于对照组患者,ET-1水平则低于对照组患者,差异均具有统计学意义(均P<0.05);治疗1个月后,观察组患者血清RBP4、Apelin水平分别为(26.58±5.04)μg/mL和(236.32±61.56)ng/L,相比治疗前均降低,且低于治疗后对照组患者的(32.72±4.29)μg/mL和(325.16±62.73)ng/L,差异均具有统计学意义(均P<0.05);观察组患者低血糖、羊水过多、胎膜早破和妊娠期高血压疾病的发生率均明显低于对照组患者,其早产儿、其新生儿窒息和新生儿死胎的发生率均明显低于对照组新生儿,其新生儿出生体重明显高于对照组,差异具有统计学意义(P<0.05),两组患者剖宫产率及新生儿高胆红素血症、巨大儿的发生率与对照组相比,差异均无统计学意义(均P>0.05)。结论妊娠糖尿病患者胰岛素抵抗的发生与RBP4、Apelin血清水平有关,而盐酸二甲双胍联合门冬胰岛素治疗妊娠糖尿病能明显改善患者血清RBP4、Apelin水平,改善胰岛素抵抗程度,同时还能降低脐血流阻力,进而改善生产结局,其治疗安全有效,值得临床推广应用。

Objective To observe the effect of metformin hydrochloride combined with insulin aspart on the insulin resistance and pregnancy outcomes of patients with gestational diabetes mellitus(GDM).Methods A total of 106 GDM patients treated in Rizhao Hospital of Traditional Chinese Medicine from July 2016 to February 2019 were randomly divided into control group(53 cases)and observation group(53 cases).All the patients in the two groups were given subcutaneous injection of insulin aspart,on which basis,the observation group received administration of metformin hydrochloride.Fasting blood glucose(FPG),fasting insulin(FINS),serum RBP4 and Apelin levels were compared between the two groups before and after 1 months of treatment.The level of insulin resistance[steady mode insulin resistance index(HOMA-IR),homeostasis mode insulin secretion index(HOMA-β),insulin sensitivity index(ISIcomp)],resistance parameters of umbilical blood flow,serum nitric oxide(NO)level and serum endothe-lin-1(ET-1)level in the two groups after 1 month of treatment were compared.The pregnancy and neonatal condition of the two groups were recorded and compared.Results After treatment,the FPG and FINS in the observation group were(4.57±1.02)mmol/L and(14.39±2.31)mIU/L,respectively,which were significantly lower than those be-fore treatment,and significantly lower than those in the control group[(5.26±1.14)mmol/L,(17.65±2.23)mIU/L],all with statistically significant differences(all P<0.05).After 1 month of treatment,the HOMA-IR and HOMA-βin the observation group were significantly lower than those in the control group,while the ISIcomp was sig-nificantly higher than that in the control group,with statistically significant differences(all P<0.05).The umbilical artery ultrasound parameters in the observation group were significantly lower than those in the control group,the serum NO level in the observation group was significantly higher than that in the control group,while the ET-1 level in the observation group was significantly lower than that in the control group,with statistically significant differences(all P<0.05).After 1 month of treatment,serum RBP4,Apelin level of the observation group were(26.58±5.04)g/mL and(236.32±61.56)ng/L,which were significantly lower than those before treatment,and significantly lower than those in the control group[(32.72±4.29)g/mL,(325.16±62.73)ng/L],all with statistically significant differences(all P<0.05).The incidence of hypoglycemia,excessive amniotic fluid,premature rupture of membranes and pregnancy induced hypertension in the observation group were significantly lower than those of the control group,the incidence of premature infants,neonatal asphyxia and neonatal stillbirth were significantly lower than those of the control group,and the birth body mass of the newborns was significantly higher than that of the control group,with statistically significant differences(P<0.05).There were no statistically significant differences in the incidence of neonatal hyperbilirubinemia and macrosomia between the two groups(all P>0.05).Conclusions The occurrence of insulin resistance in patients with gestational diabetes mellitus is related to the serum levels of RBP4 and Apelin.Met-formin hydrochloride combined with insulin asparagus in the treatment of gestational diabetes mellitus can significantly improve the serum levels of RBP4 and Apelin,improve insulin resistance,reduce umbilical blood flow resistance,and improve production solutions,safe and effective and worthy of clinical application.