Department of Obstetrics and Gynaecology, Università Cattolica del Sacro Cuore, Rome, Italy.
Diabetes Care. 2013 Jun;36(6):1477-82. doi: 10.2337/dc12-2071. Epub 2013 Jan 11.
Metformin has been reported to reduce the risk of gestational diabetes (GD) in women with polycystic ovarian syndrome (PCOS). However, little is known about the mechanisms of action of this drug during pregnancy. In the attempt to fill this gap, we performed a prospective longitudinal study providing a detailed examination of glucose and insulin metabolism in pregnant women with PCOS undergoing metformin therapy.
We enrolled 60 women with PCOS who conceived while undergoing metformin treatment. An oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp were performed at each trimester of gestation in 47 ongoing pregnancies.
Twenty-two of the study subjects had development of GD despite the treatment. At baseline, insulin sensitivity was comparable between women who had development of GD and women who did not. A progressive decline in this parameter occurred in all subjects, independently of the trimester of GD diagnosis. Insulin secretion was significantly higher during the first trimester in patients with an early failure of metformin treatment. Women with third trimester GD and women with no GD exhibited a significant increase in insulin output as gestation proceeded. All newborns were healthy and only one case of macrosomia was observed.
Women with PCOS who enter pregnancy in a condition of severe hyperinsulinemia have development of GD earlier, independently of metformin treatment. The physiologic deterioration of insulin sensitivity is not affected by the drug and does not predict the timing and severity of the glycemic imbalance. Despite the high incidence of GD observed, the drug itself or the intensive monitoring probably accounted for the good neonatal outcome.
有报道称二甲双胍可降低多囊卵巢综合征（PCOS）女性的妊娠期糖尿病（GD）风险。然而，关于该药在妊娠期间的作用机制知之甚少。为了填补这一空白，我们进行了一项前瞻性纵向研究，对接受二甲双胍治疗的 PCOS 孕妇的葡萄糖和胰岛素代谢进行了详细检查。
我们招募了 60 名正在接受二甲双胍治疗并怀孕的 PCOS 女性。47 例持续妊娠的孕妇在每个孕期均进行口服葡萄糖耐量试验和正葡萄糖高胰岛素钳夹试验。
22 名研究对象尽管接受了治疗，但仍出现 GD。在基线时，GD 组和非 GD 组的胰岛素敏感性相似。所有受试者的这一参数均呈进行性下降，与 GD 诊断的孕期无关。在接受二甲双胍早期治疗失败的患者中，在孕早期胰岛素分泌显著增加。随着孕期的进展，有第三孕期 GD 的女性和无 GD 的女性胰岛素分泌量显著增加。所有新生儿均健康，仅观察到一例巨大儿。
患有 PCOS 的女性在严重高胰岛素血症的情况下进入妊娠，无论是否接受二甲双胍治疗，都会更早出现 GD。胰岛素敏感性的生理性恶化不受药物影响，也不能预测血糖失衡的时间和严重程度。尽管观察到 GD 发病率较高，但药物本身或强化监测可能是良好的新生儿结局的原因。
