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Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Barnendokrinologisk forskning/Tuvemo)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Barnendokrinologisk forskning/Tuvemo)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Barnendokrinologisk forskning/Tuvemo)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Barnendokrinologisk forskning/Tuvemo)
2007 (English)In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 120, no 5, 958-965 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE. In addition to neonatal hypoglycemia, infants who are born large for gestational age are at risk for developing obesity, cardiovascular disease, and diabetes later in life. The aim of this study was to investigate glucose production, lipolysis, and insulin sensitivity in infants who were born large for gestational age to mothers without diabetes. The effect of glucagon administration on production of energy substrates was also investigated.

METHODS. Ten healthy term infants who were born large for gestational age to mothers without diabetes were studied 16 ± 8 hours postnatally after a 3-hour fast. Rates of glucose production and lipolysis were analyzed by gas chromatography–mass spectrometry following constant rate infusion of [6,6-2H2]glucose and [2-13C]glycerol. Insulin sensitivity was assessed by the Homeostasis Assessment Model. In 8 of the infants, the effect of an intravenous injection of 0.2 mg/kg glucagon was also analyzed.

RESULTS. Plasma glucose and glycerol averaged 3.8 ± 0.5 mmol/L and 384 ± 183 µmol/L, respectively. The glycerol production rate, reflecting lipolysis, was 12.7 ± 2.9 µmol/kg per min. Mean rate of glucose production was 30.2 ± 4.6 µmol/kg per min. Homeostasis Assessment Model insulin sensitivity corresponded to 82% ± 19%, β-cell function to 221% ± 73%, and insulin resistance to 1.3 ± 0.3. After glucagon administration, rate of glucose production increased by 13.3 ± 8.3 µmol/kg per min and blood glucose by 1.4 ± 0.5 mmol/L. Glycerol production decreased from 12.8 ± 3.0 to 10.7 ± 2.9 µmol/kg per min. Mean insulin concentration increased from 10.9 ± 3.0 to 30.9 ± 10.3 mU/L. There was a strong inverse correlation between the decrease in lipolysis and increase in insulin after glucagon administration.

CONCLUSIONS. Infants who are born large for gestational age show increased lipolysis and a propensity for decreased insulin sensitivity already at birth. The simultaneous increase in plasma insulin correlated strongly with the noted decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants.

Place, publisher, year, edition, pages
2007. Vol. 120, no 5, 958-965 p.
Keyword [en]
LGA, glucose production, lipolysis, newborn infant, insulin sensitivity
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97381DOI: 10.1542/peds.2007-0165ISI: 000250618900004PubMedID: 17974732OAI: oai:DiVA.org:uu-97381DiVA: diva2:172311
Available from: 2008-08-18 Created: 2008-08-18 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Being Born Large for Gestational Age: Metabolic and Epidemiological Studies
Open this publication in new window or tab >>Being Born Large for Gestational Age: Metabolic and Epidemiological Studies
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity is a major health problem in the Western world. Mean birth weight has increased during the last 25 years. One explanation is that the proportion of large for gestational age (LGA) infants has increased. Such infants risk developing obesity, cardiovascular disease and diabetes later in life. Despite the risk of neonatal hypoglycemia, their postnatal metabolic adaptation has not been investigated. Our data, obtained with stable isotope labeled compounds, demonstrate that newborn LGA infants have increased lipolysis and decreased insulin sensitivity. After administration of glucagon, the plasma levels of glucose and the rate of glucose production increased. The simultaneous increase in insulin correlated with the decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants.

We also demonstrated an intergenerational effect of being born LGA, since women born LGA, were at higher risk of giving birth to LGA infants than women not born LGA. Further, the LGA infants formed three subgroups: born long only, born heavy only, and born both long and heavy. Infants born LGA of women with high birth weight or adult obesity were at higher risk of being LGA concerning weight alone, predisposing to overweight and obesity at childbearing age. In addition we found that pregnant women with gestational diabetes were at increased risk of giving birth to infants that were heavy alone. This could explain the risk of both perinatal complications and later metabolic disease in infants of this group of women.

To identify determinants of fetal growth, 20 pregnant women with a wide range of fetal weights were investigated at 36 weeks of gestation. Maternal fat mass was strongly associated with insulin resistance. Insulin resistance was related to glucose production, which correlated positively with fetal size. The variation in resting energy expenditure, which was closely related to fetal weight, was largely explained by BMI, insulin resistance, and glucose production. Lipolysis was not rate limiting for fetal growth in this group of women. Consequently, high maternal glucose production due to a high fat mass may result in excessive fetal growth.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2008. 83 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 363
Keyword
large for gestational, glucose production, lipolysis, insulin resistance, intergenerational, gestational diabetes mellitus, stable isotopes, pregnant women, newborn infant
National Category
Other Medical Sciences not elsewhere specified
Identifiers
urn:nbn:se:uu:diva-9135 (URN)978-91-554-7246-7 (ISBN)
Public defence
2008-09-12, Rosénsalen, Akademiska Sjukhuset, Ingång 95/96, Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-08-18 Created: 2008-08-18Bibliographically approved

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Diderholm, BarbroEwald, UweGustafsson, Jan

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