Chronic Hyperglycemia Reduces Surface Active Material Flux in Tracheal Fluid of Fetal Lambs

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Abstract

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 μU/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 μU/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 μU/ml). Arterial blood gases (pH 7.34±0.01, Po2 24.3±0.5 mmHg, Pco2 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 μg/g per h) was statistically lower than SAM flux in the control fetuses (60±9 μg/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.

Authors

David Warburton