Department of Obstetrics and Gynecology, University of Turku, 20014, Turku, Finland.
Department of Obstetrics and Gynecology, Turku University Hospital, Kiinamyllynkatu 4-8, FI-20521, Turku, Finland.
BMC Pregnancy Childbirth. 2020 Jul 11;20(1):401. doi: 10.1186/s12884-020-03077-6.
Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes.
This is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined.
In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p < 0.0001) and all IGFBP-1 phosphoisoforms (p < 0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain.
Metformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures.
The trial comparing metformin and insulin treatment was registered in ClinicalTrials.gov ( NCT01240785 ) November 3, 2010. Retrospectively registered.
妊娠糖尿病（GDM）的特征是葡萄糖代谢紊乱和低度炎症激活。我们研究了二甲双胍治疗与胰岛素治疗相比，对 GDM 患者的炎症标志物和胰岛素样生长因子结合蛋白 1（IGFBP-1）是否有有利或不利的影响，以及这些标志物是否与主要的母婴或胎儿临床结局相关。
这是一项先前比较二甲双胍（n=110）和胰岛素（n=107）治疗 GDM 的随机对照试验的二次分析。在诊断时（基线，平均 30 孕周[gw]）和 36 gw 时采集空腹血清样本。测定血清高敏 C 反应蛋白（hsCRP）、白细胞介素 6（IL-6）、基质金属蛋白酶 8（MMP-8）和糖基化蛋白（GlycA）以及三种 IGFBP-1 磷酸化异构体浓度等炎症标志物。
在二甲双胍和胰岛素组联合治疗中，hsCRP 降低（p=0.01），而 IL-6（p=0.002）、GlycA（p<0.0001）和所有 IGFBP-1 磷酸化异构体（p<0.0001）从基线增加到 36 gw。与胰岛素治疗相比，二甲双胍治疗患者的 GlycA（p=0.02）和非磷酸化 IGFBP-1（p=0.008）增加更多。炎症标志物与妊娠结局无明显关联，但非磷酸化 IGFBP-1 与妊娠体重增加呈负相关。
与胰岛素相比，二甲双胍对母体血清 IGFBP-1 浓度有有益影响，因为增加的 IGFBP-1 与总孕期和晚期母体体重增加较低有关。与胰岛素治疗相比，二甲双胍治疗时 GlycA 增加更多。这一观察结果的意义需要在进一步的研究中更深入地探讨。炎症标志物与妊娠结局测量指标之间没有明显的临床相关关系。
比较二甲双胍和胰岛素治疗的试验于 2010 年 11 月 3 日在 ClinicalTrials.gov（NCT01240785）注册。回顾性注册。
