Glueck C J, Goldenberg N, Wang P, Loftspring M, Sherman A
Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229, USA.
Hum Reprod. 2004 Mar;19(3):510-21. doi: 10.1093/humrep/deh109. Epub 2004 Jan 29.
In a prospective observational study of 42 pregnancies in 39 Caucasian women (age 30 +/- 4 years) with polycystic ovary syndrome (PCOS), we examined effects of metformin on maternal insulin, insulin resistance (IR), insulin secretion (IS), weight gain, development of gestational diabetes (GD), testosterone and plasminogen activator inhibitor activity. We assessed the hypothesis that diet-metformin (MET) lessens the physiological gestational increase in IR and reduces gestational weight gain, thus reducing GD.
Preconception, in an out-patient clinical research centre, MET 1.5 (eight pregnancies) to 2.55 g/day (34 pregnancies) was started. Women with body mass index <25 or >or=25 kg/m(2) were given a 2000 or 1500 calorie/day, high-protein (26% of calories), low-carbohydrate (44%) diet. Calorie restrictions were dropped after conception.
On MET, GD developed in three out of 42 pregnancies (7.1%). Median entry weight (94.5 kg) fell to 82.7 on MET at the last preconception visit (P = 0.0001), fell further to 81.6 during the first trimester, was 83.6 in the second trimester, and 89.1 kg in the third trimester. Median weight gain during pregnancy was 3.5 kg. The median percentage reduction in serum insulin was 40% on MET at the last preconception visit; insulin did not increase in the first or second trimesters (P > 0.05), and rose 10% in the third trimester. The median percentage reduction in HOMA IR was 46% on MET at the last preconception visit; IR did not increase (P > 0.05) in the first, second or third trimesters. HOMA insulin secretion fell 45% on MET at the last preconception visit, did not increase in the first trimester, rose 24% in the second trimester, and rose 109% in the third trimester. Testosterone fell 30% on MET at the last preconception visit (P = 0.01) and then rose 74, 61 and 95% during trimesters 1, 2 and 3; median testosterone during the third trimester did not differ from pre-treatment levels.
By reducing preconception weight, insulin, IR, insulin secretion and testosterone, and by maintaining these insulin-sensitizing effects throughout pregnancy, MET-diet reduces the likelihood of developing GD, and prevents androgen excess for the fetus.
在一项针对39名患有多囊卵巢综合征（PCOS）的白人女性（年龄30±4岁）的42次妊娠的前瞻性观察研究中，我们研究了二甲双胍对母体胰岛素、胰岛素抵抗（IR）、胰岛素分泌（IS）、体重增加、妊娠期糖尿病（GD）的发生、睾酮和纤溶酶原激活物抑制剂活性的影响。我们评估了以下假设：饮食 - 二甲双胍（MET）可减轻IR在孕期的生理性升高，并减少孕期体重增加，从而降低GD的发生。
在门诊临床研究中心，孕前开始服用MET，剂量为1.5（8次妊娠）至2.55克/天（34次妊娠）。体重指数<25或≥25kg/m²的女性分别给予2000或1500卡路里/天、高蛋白（占卡路里的26%）、低碳水化合物（44%）的饮食。受孕后不再限制热量摄入。
在服用MET期间，42次妊娠中有3次发生GD（7.1%）。末次孕前访视时的平均初始体重（94.5kg）在服用MET后降至82.7kg（P = 0.0001），孕早期进一步降至81.6kg，孕中期为83.6kg，孕晚期为89.1kg。孕期平均体重增加3.5kg。末次孕前访视时，服用MET后血清胰岛素中位数降低40%；孕早期和孕中期胰岛素水平未升高（P>0.0５），孕晚期升高10%。末次孕前访视时，服用MET后HOMA-IR中位数降低46%；孕早期、孕中期和孕晚期IR均未升高（P>0.05）。末次孕前访视时，服用MET后HOMA胰岛素分泌降低45%，孕早期未升高，孕中期升高24%，孕晚期升高109%。末次孕前访视时，服用MET后睾酮降低30%（P = 0.01），然后在孕1、2、3期分别升高74%、61%和95%；孕晚期睾酮中位数与治疗前水平无差异。
通过降低孕前体重、胰岛素、IR、胰岛素分泌和睾酮，并在整个孕期维持这些胰岛素增敏作用，MET-饮食降低了发生GD的可能性，并防止胎儿雄激素过多。
