Neufeld N, Melmed S
J Clin Invest. 1981 Dec;68(6):1605-9. doi: 10.1172/jci110417.
Diabetes mellitus in pregnancy is associated with neonatal respiratory distress syndrome due to impaired synthesis of fetal lung surfactant. Pharmacologic agents that promote fetal lung maturity are diabetogenic and have limited use in the management of diabetic pregnancy for prevention of respiratory distress syndrome. Maternal administration of a thyroid analog 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) results in significant enhancement of fetal lung phospholipid synthesis and accelerated lung maturity. We therefore studied the effects of DIMIT (0.5 mg/kg per d, s.c.) administration to pregnant alloxan-diabetic rabbits on days 25 and 26 of gestation. DIMIT treatment of diabetic maternal rabbits (DD) was associated with reduction of maternal blood glucose (115 +/- 13 vs. 275 +/- 72 mg/dl, P less than 0.05) and fetal glucose (64 +/- 6 vs. 274 +/- 47 mg/dl, P less than 0.001) compared with saline-injected diabetic (D) mothers. Reduction of fetal insulin levels was also associated with maternal DIMIT therapy in diabetic rabbits (56 +/- 5 (D) vs. 24 +/- 4 microunits/ml, P less than 0.001). Maternal diabetes resulted in significant reduction of fetal lung weight (370 +/- 20 vs. 520 +/- 30 mg, P less than 0.005) and lung protein content (6.5 +/- 0.7 vs. 8.7 +/- 0.7 mg/gm, P less than 0.005), which were restored to normal in offspring of DIMIT-treated diabetic rabbits. Maternal DIMIT administration caused significant reduction in fetal lung glycogen content in control (62 +/- 5.8 vs. 25 +/- 5.9 micrograms/mg protein, P less than 0.001) and diabetic (56 +/- 7 vs. 34 +/- 5 micrograms/mg protein, P less than 0.02) offspring. Whereas maternal diabetes was associated with reduction of all major phospholipid species in fetal lung-comprising surfactant, these were restored with DIMIT therapy. The results demonstrate that short-term maternal administration of DIMIT in pregnant diabetic rabbits not only promotes fetal lung phospholipid synthesis, but also appears to ameliorate maternal hyperglycemia. Thus, DIMIT is of potential benefit in the management of diabetic pregnancy.
妊娠期糖尿病与新生儿呼吸窘迫综合征有关，这是由于胎儿肺表面活性物质合成受损所致。促进胎儿肺成熟的药物具有致糖尿病作用，在糖尿病妊娠管理中用于预防呼吸窘迫综合征的应用有限。母体给予甲状腺类似物3,5 - 二甲基 - 3'-异丙基 - L - 甲状腺素（DIMIT）可显著增强胎儿肺磷脂合成并加速肺成熟。因此，我们研究了在妊娠第25天和第26天给妊娠的四氧嘧啶糖尿病兔皮下注射DIMIT（0.5mg/kg/天）的效果。与注射生理盐水的糖尿病（D）母亲相比，DIMIT治疗糖尿病母体兔（DD）可使母体血糖（115±13 vs. 275±72mg/dl，P＜0.05）和胎儿血糖（64±6 vs. 274±47mg/dl，P＜0.001）降低。胎儿胰岛素水平的降低也与糖尿病兔的母体DIMIT治疗有关（56±5（D） vs. 24±4微单位/毫升，P＜0.001）。母体糖尿病导致胎儿肺重量显著降低（370±20 vs. 520±30mg，P＜0.005）和肺蛋白含量降低（6.5±0.7 vs. 8.7±0.7mg/gm，P＜0.005），而在DIMIT治疗的糖尿病兔后代中这些指标恢复正常。母体给予DIMIT可使对照（62±5.8 vs. 25±5.9微克/毫克蛋白，P＜0.001）和糖尿病（56±7 vs. 34±5微克/毫克蛋白，P＜0.02）后代的胎儿肺糖原含量显著降低。虽然母体糖尿病与胎儿肺中构成表面活性物质的所有主要磷脂种类减少有关，但这些在DIMIT治疗后得以恢复。结果表明，在妊娠糖尿病兔中短期母体给予DIMIT不仅能促进胎儿肺磷脂合成，而且似乎能改善母体高血糖。因此，DIMIT在糖尿病妊娠管理中具有潜在益处。
