Warburton D
J Clin Invest. 1983 Mar;71(3):550-5. doi: 10.1172/jci110799.
I tested the hypothesis that chronic hyperglycemia alters fetal lung maturation by continuous infusion of glucose (14+/-2 mg/kg per min, mean+/-SE) from 112 up to 145 d gestation into six chronically catheterized fetal lambs from which tracheal fluid could be collected. Serum glucose levels (32+/-2 mg/dl) and serum insulin levels (38+/-4 muU/ml) in these glucose-treated fetuses were significantly higher than serum glucose levels (18+/-2 mg/dl, P < 0.001) and serum insulin levels (12+/-3 muU/ml, P < 0.001) in six chronically catheterized control fetuses of the same gestational ages. Glucose infusion to the fetuses did not alter maternal serum glucose (60+/-3 mg/dl) or serum insulin levels (35+/-5 muU/ml). Arterial blood gases (pH 7.34+/-0.01, Po(2) 24.3+/-0.5 mmHg, Pco(2) 41.5+/-0.9 mmHg), oxygen saturation (73+/-2%), hematocrit (31+/-1%), and tracheal fluid flow (2.4+/-0.1 ml/g per h) in the glucose-treated fetuses were not significantly different from controls. Among the control fetuses, surface active material (SAM) began to appear in tracheal fluid at 123 d gestation and was present in all six fetuses by 129 d gestation, whereas SAM did not appear at all in tracheal fluid of four of the glucose-treated fetuses, and appeared in two at low levels after 142 d gestation. SAM flux in the glucose-treated fetuses (<1 mug/g per h) was statistically lower than SAM flux in the control fetuses (60+/-9 mug/kg per h, P < 0.001). Between 130 and 140 d gestation, tracheal fluid phospholipid content rose fourfold, mixed lecithin content rose ninefold, disaturated phosphatidylcholine content rose fourfold in the control fetuses, whereas little or no increase in these measurements occurred in the glucose-treated fetuses (all differences significant). I conclude that chronic hyperglycemia with secondary hyperinsulinemia reduces SAM flux in tracheal fluid of fetal lambs. The reduction in SAM flux is attributed to low surface active phospholipid content of the SAM. A similar mechanism may operate in utero to cause respiratory distress in infants of diabetic mothers whose maternal glucose homeostasis is poorly controlled.
我通过对6只长期插管的胎羊持续输注葡萄糖（14±2毫克/千克每分钟，均值±标准误），从妊娠112天至145天，收集气管液体，来验证慢性高血糖会改变胎儿肺成熟的假说。这些接受葡萄糖治疗的胎儿的血清葡萄糖水平（32±2毫克/分升）和血清胰岛素水平（38±4微单位/毫升）显著高于6只相同胎龄的长期插管对照胎儿的血清葡萄糖水平（18±2毫克/分升，P<0.001）和血清胰岛素水平（12±3微单位/毫升，P<0.001）。向胎儿输注葡萄糖并未改变母体血清葡萄糖（60±3毫克/分升）或血清胰岛素水平（35±5微单位/毫升）。接受葡萄糖治疗的胎儿的动脉血气（pH 7.34±0.01，氧分压24.3±0.5毫米汞柱，二氧化碳分压41.5±0.9毫米汞柱）、氧饱和度（73±2%）、血细胞比容（31±1%）和气管液体流量（2.4±0.1毫升/克每小时）与对照组无显著差异。在对照胎儿中，表面活性物质（SAM）在妊娠123天时开始出现在气管液体中，到妊娠129天时在所有6只胎儿中均有出现，而在4只接受葡萄糖治疗的胎儿的气管液体中SAM根本未出现，另外2只在妊娠142天后才出现少量。接受葡萄糖治疗的胎儿的SAM通量（<1微克/克每小时）在统计学上低于对照胎儿的SAM通量（60±9微克/千克每小时，P<0.001）。在妊娠130天至140天期间，对照胎儿的气管液体磷脂含量增加了四倍，混合卵磷脂含量增加了九倍，二饱和磷脂酰胆碱含量增加了四倍，而接受葡萄糖治疗的胎儿在这些测量指标上几乎没有增加或没有增加（所有差异均显著）。我得出结论，慢性高血糖伴继发性高胰岛素血症会降低胎羊气管液体中的SAM通量。SAM通量的降低归因于SAM中表面活性磷脂含量较低。类似的机制可能在子宫内起作用，导致母体葡萄糖稳态控制不佳的糖尿病母亲的婴儿出现呼吸窘迫。
