3,5-Dimethyl-3'-isopropyl-L-thyronine therapy in diabetic pregnancy. Stimulation of rabbit fetal lung phospholipids

Abstract

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 reduction of maternal blood glucose (64±6 vs. 274±47 mg/dl, P <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 μU/ml, P <0.001). Maternal diabetes resulted in significant reduction of fetal lung weight (370±20 vs. 520±30 mg, P <0.005) and lung protein content (6.5±0.7 vs. 8.7±0.7 mg/gm, P <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 μg/mg protein, P <0.001) and diabetic (56±7 vs. 34±5 μg/mg protein, P <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.