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DISORDERS OF GLUCOSE METABOLISM

Normal postnatal glucose homeostasis is established by increased glucose production and utilization. Factors that promote glucose production include catecholamines and glucagon, which activate glycogenolysis. A high glucagon-to-insulin ratio, which induces synthesis and activity of the enzymes, is required for there to be gluconeogenesis. Once normal feedings are established, glycerol and amino acids continue to fuel gluconeogenesis while dietary fatty acids activate the enzymes responsible for gluconeogenesis. Additionally, galactose derived from the hydrolysis of milk sugar (lactose) in the gut increases hepatic glycogen production for sustained between-feeding hepatic glucose release from glycogen breakdown. Feeding also induces production of intestinal peptides, or incretins, that promote insulin secretion. Insulin decreases hepatic glucose production and increases glucose utilization for energy production and storage as glycogen. These opposing conditions of glucose production and utilization continue in response to normal feed-fast cycles, regulating normal plasma glucose concentrations.

HYPOGLYCEMIA

Glucose is the major source of energy for organ function. All organs use glucose, and glucose deficiency leads to impaired cardiac performance, cerebral energy failure, hepatic glycogen depletion, and muscle weakness. Cerebral glucose metabolism accounts for as much as 90% of total glucose consumption in the newborn. Thus, maintenance of glucose delivery to all organs, particularly the brain, is an essential physiological function. Although alternate fuels can substitute for glucose metabolism, concentrations of these substances often are low in newborn infants, especially preterm infants. Newborns, therefore, are especially susceptible to hypoglycemia when they are exposed to conditions that impair glucose homeostasis during the transition from intrauterine to extrauterine life.

DEFINITION

Ideally, hypoglycemia should be defined as a glucose concentration below the lower limit of the normal range of blood or plasma/serum glucose concentrations. This concentration, however, is uncertain, controversial, and is variably defined. Early statistical evaluations in term infants historically defined hypoglycemia as a blood glucose concentration below 35 mg/dL, or a plasma glucose value below 40 mg/dL; and even lower concentrations were applied in preterm infants. Such statistical definitions, however, have limited biological or clinical significance. This is because physiological hypoglycemia is present when the concentration of glucose in the plasma yields glucose delivery rates that are inadequate to meet essential requirements for glucose utilization, which vary considerably. Definitions of normal and hypoglycemic glucose concentrations vary according to postnatal feeding practices and timing of the measurement. Postnatally, the blood glucose concentration normally decreases to its lowest value between 1 and 3 hours after birth, followed by a progressive increase to greater than 50 to 60 mg/dL by 12 to 24 hours (Fig. 53-1).

Figure 53-1

Plasma glucose concentrations during the first week of life in healthy, appropriate-for-gestational-age term infants.

The absolute glucose concentration below which short- or long-term organ dysfunction occurs remains undefined, although animal studies suggest that concentrations below 20 mg/dL ...

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