Effects of a sustained insulin infusion upon glucose uptake and oxygenation of the ovine fetus.

Abstract

Summary: The effect of insulin upon fetal metabolism is an important question to resolve, bearing in mind that the metabolic effects of insulin on the fetus could differ both quantitatively and qualitatively depending upon the degree and duration of the hyperinsulinemia. The present study was designed to determine whether the effect of fetal hyperinsulinemia on umbilical glucose uptake could be sustained over several days of infusion with various levels of insulin. An unexpected outcome of the study was the observation that this procedure was accompanied by the development of fetal hypoxia. Fetal glucose/oxygen quotients (G/O2) increased during fetal insulin infusions from a mean of 0.48 during the control period to 0.71 when fetal insulin levels were less than 80 micro units/ml (P < 0.01) and to 0.85 when fetal insulin levels were greater than 200 micro units/ml (P < 0.001). The increase in G/O2 occurred within 4 hr of infusion in all cases (P < 0.005) and was sustained for the duration of the infusions. The increase in G/O2 was due to a significant rise in the arteriovenous differences of whole blood glucose across the umbilical circulation (P < 0.001). Oxygen content differences across the umbilical circulation also increased during infusion (P < 0.005). This was due primarily to a significant and progressive decline in the fetal arterial oxygen content (P < 0.001). By 24 hr after the insulin had been stopped, the oxygen content rose and returned to pre-infusion values by the 3rd day of recovery. Fetal plasma glucose concentration fell during insulin infusion (P < 0.001) and rebounded sharply to levels significantly higher than control values (P < 0.001) within 4 hr after the infusion was stopped. The plasma glucose returned to control values by the 3rd day of recovery. Insulin levels ranged from 0–16 micro units/ml during control periods and from 48–1166 micro units/ml during infusion. There was a significant positive correlation between the G/O2 quotient and the log of fetal insulin concentration. There was a negative correlation between the fetal arterial oxygen content and insulin concentration. Five twin pairs were studied in which one twin served as control and the other as the infusion subject. The values of glucose, G/ O2, and arteriovenous differences of glucose and oxygen were significantly different between the infused and control twin fetuses within 4 hr of infusion and the oxygen content was significantly lower in the infused twin by 24 hr of infusion. There were no significant differences in these measurements between the twins before infusion. Speculation: Insulin infusions of several days duration into the fetal lamb cause a sustained increase in umbilical glucose uptake and a decrease in fetal arterial oxygen content. The progressive decline in fetal arterial oxygen content during infusion may be due to an increase in fetal oxygen consumption. The effect of insulin upon fetal oxygenation may be one of the pathophysiologic factors contributing to the increased intrauterine death rate of infants of diabetic mothers.