Abnormal expression of glucose-6-phosphatase in preterm infants.

Hume, Robert; Burchell, Ann

doi:10.1136/adc.68.2.202

Cited by 55 publications

(27 citation statements)

References 23 publications

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“…glucose-6-phosphatase), rather than a defect in either gluconeogenesis or glycogenolysis. This hypothesis is consistent with the in vitro findings of Hume et al (42) of a low glucose-6-phosphatase activity in hepatocytes of preterm infants. Glucose-6-phosphatase catalyzes the final step of hepatic gluconeogenesis and glycogenolysis.…”

Section: Discussionsupporting

confidence: 82%

Adaptation of Glucose Production and Gluconeogenesis to Diminishing Glucose Infusion in Preterm Infants at Varying Gestational Ages

et al. 2003

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In preterm infants low plasma glucose concentrations are frequently observed. We hypothesized that the infants' ability to adapt endogenous glucose production to diminishing exogenous supply is disturbed, but will improve with increasing gestational age. Glucose production rate and gluconeogenesis were measured using stable isotope techniques with [6,6-2 H 2 ]glucose and [2-13 C]glycerol in 19 preterm infants (10 Յ 30 wk and nine Ͼ30 wk gestational age) on d 5.0 Ϯ 1.4 of life. Exogenous glucose was administered at a rate of 33 mol·kg Ϫ1 ·min Ϫ1 followed by 22 mol·kg Ϫ1 ·min Ϫ1 . In the first 2 h after the decrease in exogenous supply, plasma glucose concentration declined comparably in both groups: Յ30 wk, from 4.3 Ϯ 1.2 to 3.2 Ϯ 0.9 mM; Ͼ30 wk, from 3.7 Ϯ 0.7 to 3.0 Ϯ 0.6 mM. Thereafter, only in infants Ͼ30 wk an increase was observed, to 3.4 Ϯ 0.8 mM. Glucose production rate increased comparably in both groups: Յ30 wk, from 6.0 Ϯ 4.1 to 8.8 Ϯ 3.4 mol·kg Ϫ1 ·min Ϫ1 ; Ͼ30 wk, from 7.8 Ϯ 4.6 to 11.6 Ϯ 5.2 mol·kg Ϫ1 ·min Ϫ1 . This increase was equivalent to approximately 30% of the decline in exogenous glucose. Gluconeogenesis increased comparably in both groups: Ͻ30 wk, from 3.2 Ϯ 1.2 to 4.5 Ϯ 1.3 mol·kg Ϫ1 ·min Ϫ1 ; Ͼ30 wk, from 4.3 Ϯ 1.9 to 6.8 Ϯ 2.9 mol·kg Ϫ1 ·min Ϫ1 . We conclude that preterm infants can only partly compensate a decline in exogenous glucose supply by increasing endogenous glucose production rate, probably because of limitations in the final common pathway of intracellular glucose metabolism (i.e. glucose-6-phosphatase). The ability to maintain the plasma glucose concentration after a decrease in exogenous supply is better preserved in infants Ͼ30 wk owing to more efficient adaptation of peripheral glucose utilization. Abbreviations AGA, appropriate for gestational age CI, confidence interval GPR, (endogenous) glucose production rate MIDA, mass isotopomer distribution analysis Ra, rate of appearance SGA, small for gestational age A low plasma glucose concentration is frequently found in preterm infants, particularly during the first postnatal days, and may lead to serious short-term and long-term complications. The incidence is inversely related to declining gestational age and birth weight (1-3). Therefore, preterm infants routinely receive enteral feedings or i.v. glucose shortly after birth. Despite this policy, the incidence of hypoglycemia-defined as a plasma glucose concentration Ͻ 2.6 mM-is still approximately 20% in our neonatal intensive care unit, a referral unit for infants Յ 32 wk gestational age. The high risk of hypoglycemia may be related to limited substrate stores, a high brain-to-body weight ratio, and immature enzyme systems (4 -6).The pathophysiology of low plasma glucose concentrations in otherwise healthy preterm infants is not completely understood because of lack of sufficient data on glucose kinetics. Endogenous GPR in preterm infants of various gestational ages was measured under different circumstances (6 -18). In most studies glucose was supplied at varying rates, s...

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Section: Discussionsupporting

confidence: 82%

Adaptation of Glucose Production and Gluconeogenesis to Diminishing Glucose Infusion in Preterm Infants at Varying Gestational Ages

et al. 2003

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“…The risk of hypoglycemia is significantly greater among preterm infants because of their reduced energy and glycogen reserves and inability to mobilize alternative metabolic fuels. 496 Hypoglycemia is also relatively common among LBW infants and macrosomic infants of diabetic mothers. 497 Prevention and management of neonatal hypoglycemia have been the subjects of a major review by Williams.…”

Section: Hypoglycemia Prevention and Managementmentioning

confidence: 99%

Community-Based Interventions for Improving Perinatal and Neonatal Health Outcomes in Developing Countries: A Review of the Evidence

et al. 2005

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ABSTRACT. Background. Infant and under-5 childhood mortality rates in developing countries have declined significantly in the past 2 to 3 decades. However, 2 critical indicators, maternal and newborn mortality, have hardly changed. World leaders at the United Nations Millennium Summit in September 2000 agreed on a critical goal to reduce deaths of children <5 years by two thirds, but this may be unattainable without halving newborn deaths, which now comprise 40% of all under-5 deaths. Greater emphasis on wide-scale implementation of proven, cost-effective measures is required to save women's and newborns' lives. Approximately 99% of neonatal deaths take place in developing countries, mostly in homes and communities. A comprehensive review of the evidence base for impact of interventions on neonatal health and survival in developingcountry communities has not been reported.Objective. This review of community-based antenatal, intrapartum, and postnatal intervention trials in developing countries aimed to identify (1) key behaviors and interventions for which the weight of evidence is sufficient to recommend their inclusion in communitybased neonatal care programs and (2) key gaps in knowledge and priority areas for future research and program learning.Methods. Available published and unpublished data on the impact of community-based strategies and interventions on perinatal and neonatal health status outcomes were reviewed. Evidence was summarized systematically and categorized into 4 levels of evidence based on study size, location, design, and reported impact, particularly on perinatal or neonatal mortality. The evidence was placed in the context of biological plausibility of the intervention; evidence from relevant developed-country studies; health care program experience in implementation; and recommendations from the World Health Organization and other leading agencies.Results. A paucity of community-based data was found from developing-country studies on health status impact for many interventions currently being considered for inclusion in neonatal health programs. However, review of the evidence and consideration of the broader context of knowledge, experience, and recommendations regarding these interventions enabled us to categorize them according to the strength of the evidence base and confidence regarding their inclusion now in programs. This article identifies a package of priority interventions to include in programs and formulates research priorities for advancing the state of the art in neonatal health care.Conclusions. This review emphasizes some new findings while recommending an integrated approach to safe motherhood and newborn health. The results of this study provide a foundation for policies and programs related to maternal and newborn health and emphasizes the importance of health systems research and evaluation of interventions. The review offers compelling support for using research to identify the most effective measures to save newborn lives. It also may facilitate dialogue with policy...

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“…The activity of microsomal glucose-6-phosphatase (the final enzyme of both glycogenolysis and gluconeogenesis) has been reported to be in the low range in preterm infants [12]. Circulating levels of gluconeogenic substrates have been reported to be rather high: lactate and pyruvate concentrations are similar in preterm infants to those of term infants but alanine concentration is lower (0.18 vs. 0.26 mmol/l, p < 0.01) [7].…”

Section: Altered Glucose Metabolism In Preterm Infantsmentioning

confidence: 99%

Glucose Regulation in Preterm Newborn Infants

Mitanchez¹

2007

Horm Res Paediatr

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After birth, continuous transplacental transfer of glucose is interrupted. Neonates have to provide brain and vital organs with sufficient glucose. In term newborn infants, this is accomplished through well-coordinated hormonal and metabolic adaptive changes. During the first week of life, preterm infants are at high risk of abnormal glucose homeostasis. They are at risk of hypoglycemia due to limited glycogen and fat stores that should have occurred in the third trimester. Continuous glucose infusion is always required soon after birth to maintain the glucose level. However, under such conditions, many preterm infants develop hyperglycemia. Defective islet β-cell processing of proinsulin is likely related to hyperglycemia. There is also evidence that preterm infants are partially resistant to insulin. By contrast with adults, hepatic glucose production is not suppressed during parenteral glucose infusion. Exogenous insulin infusion partially reduces endogenous glucose production in preterm newborn infants. This treatment is efficient and safe when used with caution. More research is needed to understand the specificity of glucose homeostasis in preterm infants and to evaluate the long-term consequences of metabolic and nutritional support during early life.

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Abnormal expression of glucose-6-phosphatase in preterm infants.

Cited by 55 publications

References 23 publications

Adaptation of Glucose Production and Gluconeogenesis to Diminishing Glucose Infusion in Preterm Infants at Varying Gestational Ages

Adaptation of Glucose Production and Gluconeogenesis to Diminishing Glucose Infusion in Preterm Infants at Varying Gestational Ages

Community-Based Interventions for Improving Perinatal and Neonatal Health Outcomes in Developing Countries: A Review of the Evidence

Glucose Regulation in Preterm Newborn Infants

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