Tertti Kristiina, Laine Kari, Ekblad Ulla, Rinne Valtteri, Rönnemaa Tapani
Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland,
Acta Diabetol. 2014 Oct;51(5):731-8. doi: 10.1007/s00592-014-0570-6. Epub 2014 Mar 16.
The purpose of the study was to examine in vivo placental transfer of metformin, its association with neonatal outcome in metformin-treated gestational diabetes (GDM) patients, and influence of metformin exposure on maternal glycemic control and weight gain. Two hundred and seventeen GDM patients were randomized to metformin or insulin in Turku University Hospital, Finland. Metformin concentrations were determined by mass spectrometry in maternal serum at 36 gestational weeks (gw) and at birth, and in umbilical cord blood. Main outcome measures were birth weight, gw at birth, umbilical artery pH and neonatal hypoglycemia, maternal weight gain, HbA1c and fructosamine concentration. Median umbilical cord/maternal serum metformin concentration ratio was 0.73. There were no differences in birth weight measured in grams or SD units (p = 0.49), or gw at birth (p always ≥0.49) between insulin- and metformin-treated patients stratified by trough metformin concentration tertiles measured at 36 gw. Rate of neonatal hypoglycemia (p = 0.92) and umbilical artery pH value (p = 0.78) was similar in insulin- and metformin-treated patients stratified by cord metformin concentration tertiles. Maternal glycemic control was similar in metformin concentration tertiles at 36 gw. Maternal weight gain was 223 g greater per week (p = 0.038) in the lowest metformin tertile compared to other tertiles combined. Maternal and fetal exposure to metformin is similar. Maternal or fetal metformin concentrations do not predict maternal glycemic control or neonatal outcome, but low maternal exposure may lead to greater maternal weight gain.
本研究的目的是检测二甲双胍的体内胎盘转运情况、其与接受二甲双胍治疗的妊娠期糖尿病（GDM）患者新生儿结局的关联，以及二甲双胍暴露对母体血糖控制和体重增加的影响。芬兰图尔库大学医院将217例GDM患者随机分为二甲双胍组或胰岛素组。在孕36周（gw）、出生时以及脐血中，采用质谱法测定母体血清中的二甲双胍浓度。主要结局指标包括出生体重、出生时的孕周、脐动脉pH值和新生儿低血糖、母体体重增加、糖化血红蛋白（HbA1c）和果糖胺浓度。脐血/母体血清二甲双胍浓度中位数比值为0.73。根据孕36周时测定的二甲双胍谷浓度三分位数分层，胰岛素治疗组和二甲双胍治疗组在以克或标准差单位衡量的出生体重（p = 0.49）或出生时的孕周（p始终≥0.49）方面没有差异。根据脐血二甲双胍浓度三分位数分层，胰岛素治疗组和二甲双胍治疗组的新生儿低血糖发生率（p = 0.92）和脐动脉pH值（p = 0.78）相似。在孕36周时，不同二甲双胍浓度三分位数组的母体血糖控制情况相似。与其他三分位数组总和相比，最低二甲双胍三分位数组的母体每周体重增加多223 g（p = 0.038）。母体和胎儿对二甲双胍的暴露相似。母体或胎儿的二甲双胍浓度不能预测母体血糖控制或新生儿结局，但母体低暴露可能导致更大的母体体重增加。
