Normal Glucose Homeostasis

Concentration of glucose in the plasma is maintained in a relatively narrow range in most persons but requires a delicate balance between glucose production and use. Euglycemia is maintained if the rate of appearance of glucose into the plasma space equals the rate of disappearance. If the rate of appearance of glucose exceeds the rate of disappearance, the plasma concentration of glucose increases. If the rate of appearance of glucose is lower than the rate of disappearance, plasma concentration decreases.

Abnormalities in hormone secretion, substrate interconversion, and mobilization of metabolic fuels contribute to abnormalities in glucose production and use, which can result in hypoglycemia. Understanding the physiological mechanism of normal glucose metabolism is necessary to determine the pathophysiological mechanism of hypoglycemia and hyperglycemia.

The factors that regulate glucose homeostasis in adults and children are similar, but two aspects of glucose homeostasis are unique to the newborn infant and young child. The first concerns the transition from the intrauterine life to the first fast after delivery. The second is the high rate of glucose use in infants and children compared with that in adults.

Transition to Extrauterine Life
Glucose is rapidly transported across the placenta by means of facilitated diffusion. The result is a constant supply of glucose to the fetus. Thus the fetus is not dependent on its own glycogenolytic or gluconeogenic capability. Maternal glucose is the only source of glucose for a term infant at birth. Little is known about the time of induction of the hepatic gluconeogenic enzymes in the human fetus. Animal experiments show the activity of rate-limiting gluconeogenic enzymes (pyruvate carboxylase, phosphoenol pyruvate carboxykinase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase) is low at birth but increases rapidly during the first hours of life. However, studies with fetal sheep suggest that hepatic glucose production can be hormonally modulated to some extent in utero.

Over the last trimester of gestation, the fetus accumulates body stores of fat and glycogen, and the activity of a number of enzymes necessary for mobilization of glucose, free fatty acids, and amino acids increases. This prepares the infant for its first fast after delivery and for cessation of continuous intravenous feeding with the clamping of the umbilical cord.

At delivery, a healthy newborn infant has adequate stores of fat and glycogen to sustain a short period of caloric deprivation and is capable of mobilizing these substrates as energy sources. The postnatal decrease in respiratory quotient and increase in plasma concentrations of glycerol and free fatty acids indicate that the newborn infant is mobilizing and oxidizing fat soon after birth. During the first 2 hours after birth, the plasma concentration of glucose decreases to reach a nadir approximately 1 to 2 hours postnatally. However, the decrease in insulin and increase in plasma concentrations of glucagon, epinephrine, and GH that occurs after birth stimulate glycogenolysis, gluconeogenesis, and lipolysis. The increase in fatty acid oxidation reduces use of glucose. Collectively these changes increase glucose concentration in the blood. Because glycogen stores are limited, the neonate must become dependent on gluconeogenesis within a short time. Newborn infants are capable of gluconeogenesis from both alanine and glycerol within 4 to 8 hours of delivery.

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Henry R. Kroll, MD, and Thomas R. Maher, MD
From the Department of Anesthesiology, Henry Ford Hospital, Detroit, Michigan.

Address correspondence and reprint requests to Henry R. Kroll, MD, Department of Anesthesiology, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202-9888. Address e-mail to .(JavaScript must be enabled to view this email address).

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