The metabolic clearance rate of epinephrine in the fetus of the diabetic ewe

Delayed organ maturation is a characteristic of the fetus of the diabetic mother with poor glucose control. We hypothesized that the ovine fetal catecholamine maturation sequence would be delayed in the fetus of the diabetic ewe. Twelve pregnant ewes were rendered glucose intolerant by the administration of streptozocin at 85 to 95 days gestation. Maternal diabetic status was verified with fasting blood glucose assessments. The fetal metabolic clearance rate of epinephrine was determined at 126 to 140 days' gestation by the constant infusion of 0.1 μg epinephrine per kilogram estimated fetal weight per minute. Fetal arterial blood gas values, lactate, glucose, and insulin levels were measured before infusion; after 20, 30, and 40 minutes of epinephrine infusion; and 15, 30, and 60 minutes after cessation of infusion. Fetal plasma glucose rose significantly from a control level of 42.1 ± 8.2 to 64.6 ± 5.9 mg/dl during the epinephrine infusion (p < 0.05). Fetal insulin levels increased from a baseline of 9.2 ± 2.6 μIU/ml to 32.4 ± 18.0 in the recovery period (p < 0.05), and lactate levels similarly rose from 36.4 ± 4.8 to 52.2 ± 8.2 mg/dl (p < 0.05). The plasma epinephrine production rates did not vary significantly between fetuses <135 and 135 days' gestation (15.4 ± 1.5 vs 13.9 ± 2.0 ng/min, p > 0.5). The fetal metabolic clearance rate of epinephrine at early gestations (<135 days) was similar to that of the fetus of the nondiabetic ewe (35.3 ± 3.4 vs 28.0 ± 4.3 ml/min/kg, p > 0.2). However, at later gestations (135 days) the fetus of the diabetic ewe did not have the increase in the metabolic clearance rate previously published for the control fetus (32.0 ± 4.6 vs 133.7 ± 41.7 ml/min/kg, p < 0.05). These data appear to indicate an absence in the maturation of the metabolic clearance rate of epinephrine in the fetus of the diabetic ewe. The observed alteration in the metabolic clearance rate of epinephrine of the fetus of the diabetic ewe could potentially impair the response to stress.