Alloxan-induced diabetes mellitus in the pregnant ewe: Metabolic and cardiovascular effects on the mother and her fetus

Abstract

Diabetes mellitus was acutely produced in nine pregnant sheep by the intravenous administration of alloxan 40 mg/kg in the maternal inferior vena cava. Maternal and fetal plasma concentrations of glucose, lactate, p-hydroxybutyrate, insulin, glucagon, and Pao2, oxygen content, and pH were determined before and at days 1, 3, and 5 after the injection of alloxan. Two animals aborted between days 1 and 3 after alloxan administration. In the other animals, significant changes occurred from baseline to day 5: maternal hyperglycemia (56.8 ± 5.2 vs. 227.3 ± 54.6 mg/dl; p < 0.01), maternal hypoinsulinemia (6.2 ± 3.5 vs. 1.0 ± 0.4 wU/ml, p = 0.016); maternal hyperketonemia (p-hydroxybutyrate: 0.79 ± 0.27 vs. 4.69 ± 2.64 mmol/L, p < 0.01); fetal hyperglycemia (17.0 ± 2.6 vs. 86.0 ± 16.2 mg /dl, p < 0.001); fetal hyperinsulinemia (8.4 ± 4.5 vs. 19.2 ± 6.4 wU/ml, p < 0.001); fetal hyperketonemia (p-hydroxybutyrate: 0.03 ± 0.03 vs. 0.06 ± 0.02 mmol/L, p < 0.05); fetal hypoxemia (arterial Pot: 21.6 ± 1.8 vs. 18.0 ± 2.8 mm Hg, p < 0.05, and oxygen content: 7.1 ± 0.5 vs. 4.5 ± 1.9 vol/dl, p < 0.02). Thus alloxan administered in the pregnant ewe can produce major metabolic and endocrine derangements acutely simulating those occurring in human insulin-dependent diabetic pregnancy. (Am J Obstet Gynecol 1989;160:1239-44.)