Elsevier

Seminars in Neonatology

Volume 9, Issue 1, February 2004, Pages 37-47
Seminars in Neonatology

Review article
Selected principles of perinatal–neonatal glucose metabolism

https://doi.org/10.1016/S1084-2756(03)00113-1Get rights and content

Abstract

While the fetus is completely dependent on his/her mother for glucose and other nutrient transfer across the placenta, the adult is completely independent, especially one who is neither pregnant nor diabetic. The neonate is considered to be in a transition between the complete dependence of the fetus and the complete independence of the adult. The heterogeneity that is the hallmark of neonatal glucose metabolism is illustrated by the observation that maintenance of euglycaemia in the sick and/or low-birthweight neonate is especially difficult. This reinforces the concept that the neonate is vulnerable to carbohydrate disequilibrium. In this discussion, we shall first evaluate the definition of euglycaemia by considering the ranges for hypo- and hyperglycaemia. We shall also review the considerable literature that has been published on measurement of the rate of glucose production and the rate of glucose utilization in the neonate. This review highlights where further work is necessary to understand the developing maturation (i.e. control) of glucose homeostasis in the neonate.

Introduction

Relative to glucose metabolism, the neonate is considered to be in a transition between the complete dependence of the fetus and the complete independence of the adult. The neonate must become independent after birth, balancing between glucose deficiency and excess to maintain the euglycaemic state. Since the fetus makes no endogenous glucose in utero1and depends on his/her mother for continuous substrate delivery, there is an obvious contrast with the variable and intermittent exogenous intake orally that is the hallmark of the neonatal period and beyond. Maintenance of euglycaemia especially in the sick and/or low-birthweight neonate, is difficult. Maturation of neonatal homeostasis is influenced by the integrity of the specific pathways of intermediary metabolism important in glucose metabolism, as discussed recently.2The heterogeneity that is the hallmark of neonatal glucose metabolism is illustrated by the multiplicity of conditions producing or associated with neonatal hypo- and hyperglycaemia.3This reinforces the concept that the neonate is vulnerable to carbohydrate disequilibrium. This topic has been the subject of a number of recent reviews.4, 5

Section snippets

Euglycaemia in the neonatal period

A primary example of the heterogeneity that exists in our understanding of neonatal glucose metabolism is that there are no uniform standards accepted for specific limits of euglycaemia. The definitions of what constitute hypo- and hyperglycaemia are quite variable. It is well accepted that glucose is the major substrate of carbohydrate metabolism. At birth, the maternal supply of glucose to the neonate, by definition, ceases abruptly. While the neonatal plasma glucose concentration is usually

Hypoglycaemia in the neonatal period

Although there is a large literature that focuses on the subject of neonatal hypoglycaemia, this topic remains quite controversial.12Areas of disagreement involve definition, method/site of sampling, symptoms, significance of asymptomatic status, management and, finally, its effect on neurodevelopmental outcome.10, 13In effect, there are four possible approaches to the definition of hypoglycaemia in the neonate: statistical; clinical; neurophysiological and neurodevelopmental.

First, from a

Hyperglycemia in the neonatal period

The definition of hyperglycaemia remains equally unsettled.23However, a consensus exists that the range exceeds 6.9–8.3 mmol/l.24The pathophysiological basis for the presence of hyperglycaemia has been thoroughly discussed previously3and is summarized below.

As micropremies (i.e. neonates born weighing ≤1000 g) represent a significant percentage of the neonates cared for in the neonatal intensive care setting, glucose homeostasis was evaluated in a group of micropremies born over the period of 1

Evaluation of glucose metabolism in the neonatal period

Metabolic research in the human neonate is generally limited by several basic ethical constraints, as discussed in a recent review.25Firstly, the studies must be non-invasive or minimally so. Secondly, blood samples should be small, particularly those obtained from the very-low-birthweight neonate. Thirdly, given the limited direct access to most organ systems, the approaches used must allow extrapolation from the sampled data to metabolic processes occurring in otherwise inaccessible areas.

Evaluation of hepatic glucose production in the neonatal period

During kinetic studies utilizing stable isotopic methodology, glucose infusion, glucose absorbed from the gastrointestinal tract, glycogenolysis and gluconeogenesis may contribute collectively to the rate of glucose appearance in the metabolic pool (i.e. plasma). Only the latter two variablesreflect the endogenous rate of glucose production, primarily from the liver.

Measurement of the true rate of glucose production usually gives a good estimate of the glucose requirement of the body and the

Evaluation of glucose utilization in the neonatal period

It is important to recognize that glucose is utilized by a variety of organs/tissues that have different metabolic characteristics.41, 43Firstly, there are organs/tissues that utilize glucose independent of insulin (e.g. brain). Secondly, there are organs/tissues that increase their glucose utilization with increments in plasma glucose concentration independent of increments in plasma insulin concentration (e.g. liver, gut and erythrocytes). Thirdly, there are organs/tissues that depend on

Acknowledgements

Some of this work was supported by R01 27287, awarded to Dr Cowett by the NIH NICHD.

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