Linder Katarzyna, Schleger Franziska, Ketterer Caroline, Fritsche Louise, Kiefer-Schmidt Isabelle, Hennige Anita, Häring Hans-Ulrich, Preissl Hubert, Fritsche Andreas
Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.
Diabetologia. 2014 Jun;57(6):1192-8. doi: 10.1007/s00125-014-3217-9. Epub 2014 Mar 28.
AIMS/HYPOTHESIS: Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity.
Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined.
Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03).
CONCLUSIONS/INTERPRETATION: Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.
目的/假设：胎儿编程在2型糖尿病的发病机制中起重要作用。本研究的目的是调查口服葡萄糖耐量试验（OGTT）期间母亲的代谢变化是否会影响胎儿大脑活动。
13名健康孕妇接受了OGTT（75克）。通过在0、60和120分钟时测量葡萄糖和胰岛素来确定胰岛素敏感性。在每个时间点，用胎儿脑磁图设备记录胎儿听觉诱发电场并确定反应潜伏期。
母亲的胰岛素从空腹水平67±25 pmol/l（平均值±标准差）在摄入葡萄糖后60分钟增加到918±492 pmol/l，葡萄糖水平从4.4±0.3 mmol/l增加到7.4±1.1 mmol/l。在同一时间段内，胎儿反应潜伏期从297±99毫秒降至235±84毫秒（p = 0.01），然后一直稳定到120分钟（235±84对251±91毫秒，p = 0.39）。摄入葡萄糖后60分钟，母亲的胰岛素敏感性与胎儿反应潜伏期之间存在负相关（r = 0.68，p = 0.02）。根据母亲的胰岛素敏感性对该组进行中位数分割后，胰岛素抵抗母亲的胎儿对听觉刺激的反应比胰岛素敏感母亲的胎儿慢（283±79毫秒）（178±46毫秒，p = 0.03）。
结论/解读：母亲胰岛素敏感性较低与胎儿大脑反应较慢有关。这些发现首次证明了母亲代谢对胎儿大脑活动的直接影响，并表明中枢胰岛素抵抗可能在胎儿发育过程中被编程。
