The Effects of Chronic Fetal Hyperglycemia on Substrate Uptake by the Ovine Fetus and Conceptus

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Abstract
Hyperglycemia in fetal sheep has been shown to increase the fetal metabolic rate. Fetal venous glucose infusion was performed in eight late gestation, chronically catheterized fetal lambs to assess any changes in substrate uptake by the ovine uterus and conceptus. Fetal glucose infusion (11.9 ± 0.6 mg glucose kg−1 min−1) caused a stable increase in fetal plasma glucose concentration approximately 3-fold above baseline. The fetal glucose entry rate increased from 6.6 ± 0.7 to 9.3 ± 0.6 mg kg−1 min−1 by day 3 of infusion(p < 0.01) despite a net umbilical glucose excretion during the period of fetal hyperglycemia. Due to a concomitant increase in fetal oxygen consumption, no change in fetal glucose/O2 quotient was observed. A significant relationship was noted (p < 0.02) between the fetal glucose entry rate and the rate of fetal oxygen consumption. Fetal glucose infusion caused a decrease in uterine glucose uptake as well. No changes were observed in calculated net placental glucose uptake although the relative fetal contribution increased from net placental exit to fetus to a placental uptake amounting to 20.8 ± 5.8% of the total placental glucose uptake (p < 0.01). Although no changes in fetal lactate concentration occurred, both maternal and fetal lactate entry rates increased, the magnitude of increase being significantly related to fetal glucose concentration. Both maternal and fetal insulin concentrations rose during the period of fetal hyperglycemia and were related to the respective increases of maternal or fetal’ substrate uptakes but not to fetal oxygen consumption.I These studies suggest that glucose induces significant stimulation of fetal oxidative metabolism and that fuel needs during this period are met by accelerated fetal glucose entry as well as accelerated placental production of lactate, Superimposed hypoxemia during these circumstances might be expected to have a greater effect on fetal oxygenation and pH than during normoxemic circumstances.