Effects of chronic fetal hyperglycemia upon oxygen consumption in the ovine uterus and conceptus.

Abstract

Abstra ct. Hyperglycemia has been shown to induce arterial hypoxemia in the chronically catheterized fetal sheep. To investigate the mechanism behind this glucose-induced hypoxemia, eight pregnant ewes and their fetuses were studied. Fetal glucose infusion (1 1.9±0.6 mg glucose/kg per min) was associated with a doubling of the fetal plasma glucose concentration with concomitant elevation of the umbilical vein-distal arterial 02 content difference by 24 h of infusion (P < 0.01). Calculated fetal 02 consumption increased from 8.1±0.4 ml/kg per min in the control period to a maximum value of 10.6±0.3 ml/kg per min by third infusion day (P < 0.01), which is an increase of -30%. The degree of stimulation of fetal 02 consumption was related to the degree of fetal hyperglycemia but not to the degree of fetal hyperinsulinemia. The increase in fetal 02 consumption was accompanied by a significant increase in fetal 02 extraction with no change in either fetal 02 delivery or fetal blood 02 affinity. In addition, fetal hypercapnea with a mild fetal respiratory acidosis was induced by fetal hyperglycemia. The increase in fetal arterial Pco2 was linearly related (P < 0.001) to the magnitude of increase in fetal 02 consumption. These studies suggest that chronic fetal hyperglycemia induces a state ofaccelerated fetal oxidative metabolism and may be important in explaining the etiology behind certain unusual findings in human infants of diabetic mothers.

Direct relationship of antepartum glucose control and fetal erythropoietin in human Type 1 (insulin-dependent) diabetic pregnancy

“…The significant respiratory acidaemia observed in the group of fetuses of diabetic mothers is consistent with the latter of the two possibilities. This speculation is supported by findings of respiratory acidaemia reported in chronically hyperglycaemic and hyperinsulinaemic fetal sheep [22,35], but this has not been previously reported in human fetuses.…”

“…In a study by Philipps et al the infusion of glucose to the fetus resulted in a fall in oxygen content accompanied by a rise in fetal oxygen consumption [22]. In a separate report, these authors observed a rise in fetal plasma Ep concentration in glucoseinfused sheep fetuses in which arterial blood oxygen content had fallen by 40% or more [9].…”

“…Since plasma levels of glucose, insulin, and C-peptide are known to vary rapidly (i. e., min), they were not included in the analyses. Although it has not been conclusively shown in the human, there is animal evidence that fetal hyperglycaemia and/or hyperinsulinaemia results in fetal hypoxaemia secondary to increased oxygen consumption [22,23]. We did not attempt to make this model all-inclusive by measuring other variables associated with the pathogenesis of the diabetic pregnancy, such as those included in the "mixed nutrient" environment as detailed by Metzger and Freinkel [24].…”

Effects of Exogenous Glucose on Brain Ischemia in Ovine Fetuses

“…The higher carbon dioxide tension in the I/R-Glu group was most likely a result of accelerated fetal metabolism because of the glucose infusions (48). Small variations in arterial PaO 2 , heart rate, and mean arterial blood pressure among the study periods and groups were within normal physiologic range, and probably not of major physiologic consequences.…”

Whole-body fuel selection: ‘reproduction’

“…What, for example, are the mechanisms involved in the nutritionally-mediated embryonic programming of fetal growth and size at birth? In attempting to alleviate intrauterine growth retardation, without inducing some of the metabolic and respiratory complications associated with glucose or indeed 0 2 supplementation (Phillips et al 1984;Warburton et al 1987), is there a role for manipulating fetal amino acid metabolism? Epidemiological studies suggest that intrauterine growth retardation leads to adult hypertension (Barker, 1992); is its cause maternal malnutrition or, as suggested by Edwards et al (1993), increased fetal exposure to maternal glucocorticoids arising from a reduction in placental l l phydroxysteroid dehydrogenase (EC 1.1.1.146) activity?…”