二甲双胍联合胰岛素与单纯胰岛素治疗的血糖控制和围产结局分析:单中心糖尿病合并妊娠前瞻性队列研究

Analysis of blood glucose control and perinatal outcome of insulin combined with or without metformin: a prospective cohort study of single-center in pregestational diabetes

目的:探讨二甲双胍联合胰岛素与单纯胰岛素治疗在糖尿病合并妊娠患者中血糖控制及围产结局的差异。方法:前瞻性收集2015年1月至2018年12月孕早期在北京协和医院单中心建档、常规产检并分娩的1型糖尿病(T1DM)或2型糖尿病(T2DM)合并妊娠患者。为达到血糖控制目标,按照治疗方案分为二甲双胍联用组和单纯胰岛素组。对各组患者的血糖控制情况及围产结局进行分析。计量资料的比较采用独立样本t检验(正态分布)或Mann-Whitney U检验(偏态分布),计数资料两组间比较采用χ2检验。结果:最终入组80例患者,T1DM组41例,T2DM组39例;二甲双胍联用组21例,单纯胰岛素组59例。T1DM组孕期血糖水平总体高于T2DM组,孕早、中、晚期的HbA 1c和糖化白蛋白(GA)差异均有统计学意义(P<0.05);T1DM组孕晚期胰岛素用量较T2DM大,差异也具有统计学意义(P<0.05)。T1DM组和T2DM组在分娩孕周、剖宫产率、早产率、孕期并发症、新生儿身长、体重、1 min Apgar评分、低出生体重儿、巨大儿、新生儿低血糖、其他新生儿并发症及先天畸形等围产结局的差异无统计学意义(P>0.05)。二甲双胍联用前糖化血红蛋白(HbA 1c)和GA均较单纯胰岛素组更高(P<0.05),而联用后HbA 1c和GA差异无统计学意义(P>0.05)。二甲双胍联用组较单纯胰岛素组孕晚期胰岛素用量均更少(P<0.05)。二甲双胍联用组新生儿低血糖风险降低(P=0.032)。结论:T1DM合并妊娠时胰岛素用量较T2DM合并妊娠更大,孕期二甲双胍联合胰岛素治疗可使血糖控制改善,显著减少胰岛素用量,且可减少新生儿低血糖发生。

Objective To study the difference of blood glucose control and perinatal outcome between metformin combined with insulin and insulin alone in patients with pregestational diabetes.Methods From January 2015 to December 2018,patients with pregestational diabetes were collected in Peking Union Medical College Hospital for routine antenatal examination and delivery.The blood glucose,insulin dosage and perinatal outcome of each group were compared.The differences between the two groups were compared using Student′s t test or Mann-Whitney U test.Categorical variables were compared using Chi-square test.Results Eighty patients were enrolled,with 41 in type 1 diabetes mellitus(T1DM)group,39 in type 2 diabetes mellitus(T2DM)group,21 in metformin group and 59 in insulin group.The levels of glycosyated hemoglobin A1c(HbA1c)and glycated albumin(GA)in T1DM group were higher than those in T2DM group(P<0.05).The insulin dosage in T1DM group was higher than that in T2DM group(P<0.05).There was no significant difference in the perinatal outcome of gestational weeks,cesarean section rate,premature delivery,pregnancy complications,neonatal length,weight,1 minute Apgar score,low birth weight,macrosomia,neonatal hypoglycemia,other neonatal complications and congenital malformations between the two groups.The HbA1c and GA before metformin combination were higher than those in insulin-alone group,but there was no significant difference in HbA1c and GA after metformin combination.The insulin dosage in metformin-insulin group was lower during third trimester(P<0.05).The risk of neonatal hypoglycemia was lower than that in the insulin-alone group(P=0.032).Conclusion In pregnant women with T1DM,the dosage of insulin is higher than that in T2DM.Insulin combined with metformin can improve glucose management,significantly reduce insulin dosage and the incidence of neonatal hypoglycemia in pregestational diabetes.