Effect of Diabetes during Pregnancy on Maternal and Neonatal Bile Acid Metabolism in the Rat

Abstract
The effect of streptozotocin-induced diabetes in pregnant rats, on subsequent maternal and neonatal bile acid metabolism was investigated. Plasma glucose levels (mg%) of diabetic pregnant (DP) rats was significantly greater (p < 0.05) in comparison to control pregnant (CP) rats. Total bile acid pool (mg/100g body wt) in DP was significantly higher (p < 0.05) when compared to CP (DP, 29.42 ± 4.44 vs 8.14 ± 1.13 in CP) with a marked increase in cholic acid pool size in DP (DP, 22.65 ± 3.33 vs 3.50 ± 0.48 CP, p < 0.05). The fecal excretion of bile acid was significantly lower (p < 0.05) in DP rats when compared to CP rats. Thin-layer chromatographic analysis of bile acid conjugates at postpartum revealed a significant increase in glycine conjugates in bile from DP rats. Examination of the cholic acid pool (μg/100 g body wt) in neonates (2 days old) derived from the two groups of rats indicated a strikingly reduced pool of cholic acid in neonates derived from diabetic mothers (neonates from DP 853.45 μ 213.98 vs 3690.86 μ 797.26 in CP,p < 0.05). Plasma cholesterol levels (mg%) in neonates of diabetic mothers was also significantly (p < 0.05) reduced. This study demonstrates that the diabetic state during pregnancy not only alters maternal bile acid metabolism, but also affects fetal bile acid metabolism in utero such that the effects may persist into neonatal life.