Biochemical and morphologic maturation of fetal rat lung was studied in pregnant, diabetic rats with different levels of glucose intolerance (sub-, mildly, and severely diabetic). Fetuses were almost normoglycemic and hyperinsulinemic in subdiabetic rats, both hyperglycemic and hyperinsulinemic in mildly diabetic rats, and hyperglycemic but hypoinsulinemic in severely diabetic rats. A similar delay in type II pneumocyte differentiation and a similar decrease of disaturated phosphatidylcholine (DSPC) content in lung tissue and broncho-alveolar material recovered by lung lavage occurred in the fetuses of the three diabetic groups, independently of the severity of diabetes. Phosphatidylglycerol (PG) was decreased in fetuses from severely diabetic rats only. DSPC appeared specifically affected in fetuses of sub- and mildly diabetic groups, whereas in those of severely diabetic groups, DSPC alterations accompanied a variety of abnormalities including whole lung hypoplasia and hypotrophy and decreases of sphingomyelin, unsaturated PC, and lysoPC. The mechanisms leading to abnormal lung development could therefore be different in fetuses of sub- and mildly diabetic rats on one hand and fetuses of severely diabetic rats on the other. Since hyperinsulinemia was the prominent feature of fetal “milieu interieur” in subdiabetic rats, this study presents arguments gained from in vivo experiments for an implication of hyperinsulinemia in lung developmental retardation due to maternal diabetes. However, the decrease of PG seems to depend on increased blood glucose level in itself. Diminished lung giycogen breakdown and decreased lung triglyceride content, more pronounced in fetuses of sub- and mildly diabetic rats than in those of severely diabetic rats, suggest that in the former, the decrease of DSPC biosynthesis could be due to decreased availability of substrates because of abnormal giycogen utilization.
Fetuses from sub- and mildly diabetic rats constitute experimental models most closely resembling the human fetus of the diabetic mother with respect to circulating glucose and insulin. They appear therefore more adequate for elucidating the mechanisms of abnormal lung development in the diabetic pregnancy. In contrast, fetuses from severely diabetic rats associate very high blood glucose levels and hypoinsulinemia, which are features closer to those of adult diabetic subjects than to those of the human fetus of the diabetic mother.