Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study

Benedicte Jørgenrud (Corresponding Author), Lars C. Stene, German Tapia, Håkon Bøås, Milaim Pepaj, Jens P. Berg, Per M. Thorsby, Matej Orešič, Tuulia Hyötyläinen, Kjersti S. Rønningen

Research output: Contribution to journalArticleScientificpeer-review

3 Citations (Scopus)

Abstract

AIMS: The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes.

METHOD: Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites.

RESULTS: Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age.

CONCLUSIONS: Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.

Original languageEnglish
Pages (from-to)111-119
Number of pages9
JournalPediatric Diabetes
Volume18
Issue number2
DOIs
Publication statusPublished - 1 Mar 2017
MoE publication typeA1 Journal article-refereed

Fingerprint

Metabolome
Autoimmunity
Breast Feeding
Methionine
Autoantibodies
HLA-DR4 Antigen
Branched Chain Amino Acids
Acids
Ornithine
Isoleucine
Type 1 Diabetes Mellitus
Gas Chromatography
Tyrosine
Genotype

Keywords

  • Infant Nutritional Physiological Phenomena
  • Blood Chemical Analysis
  • Humans
  • Islets of Langerhans/immunology
  • Risk Factors
  • Breast Feeding
  • Child, Preschool
  • Metabolome
  • Infant
  • Male
  • Case-Control Studies
  • Norway
  • Diabetes Mellitus, Type 1/etiology
  • Female
  • Child
  • Longitudinal Studies
  • Infant, Newborn
  • Feeding Behavior/physiology

Cite this

Jørgenrud, B., Stene, L. C., Tapia, G., Bøås, H., Pepaj, M., Berg, J. P., ... Rønningen, K. S. (2017). Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study. Pediatric Diabetes, 18(2), 111-119. https://doi.org/10.1111/pedi.12360
Jørgenrud, Benedicte ; Stene, Lars C. ; Tapia, German ; Bøås, Håkon ; Pepaj, Milaim ; Berg, Jens P. ; Thorsby, Per M. ; Orešič, Matej ; Hyötyläinen, Tuulia ; Rønningen, Kjersti S. / Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study. In: Pediatric Diabetes. 2017 ; Vol. 18, No. 2. pp. 111-119.
@article{0a21fe90e8474d8692fca361d04b44d4,
title = "Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study",
abstract = "AIMS: The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes.METHOD: Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites.RESULTS: Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50{\%} from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age.CONCLUSIONS: Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.",
keywords = "Infant Nutritional Physiological Phenomena, Blood Chemical Analysis, Humans, Islets of Langerhans/immunology, Risk Factors, Breast Feeding, Child, Preschool, Metabolome, Infant, Male, Case-Control Studies, Norway, Diabetes Mellitus, Type 1/etiology, Female, Child, Longitudinal Studies, Infant, Newborn, Feeding Behavior/physiology",
author = "Benedicte J{\o}rgenrud and Stene, {Lars C.} and German Tapia and H{\aa}kon B{\o}{\aa}s and Milaim Pepaj and Berg, {Jens P.} and Thorsby, {Per M.} and Matej Orešič and Tuulia Hy{\"o}tyl{\"a}inen and R{\o}nningen, {Kjersti S.}",
year = "2017",
month = "3",
day = "1",
doi = "10.1111/pedi.12360",
language = "English",
volume = "18",
pages = "111--119",
journal = "Pediatric Diabetes",
issn = "1399-543X",
publisher = "Blackwell Munksgaard",
number = "2",

}

Jørgenrud, B, Stene, LC, Tapia, G, Bøås, H, Pepaj, M, Berg, JP, Thorsby, PM, Orešič, M, Hyötyläinen, T & Rønningen, KS 2017, 'Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study', Pediatric Diabetes, vol. 18, no. 2, pp. 111-119. https://doi.org/10.1111/pedi.12360

Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study. / Jørgenrud, Benedicte (Corresponding Author); Stene, Lars C.; Tapia, German; Bøås, Håkon; Pepaj, Milaim; Berg, Jens P.; Thorsby, Per M.; Orešič, Matej; Hyötyläinen, Tuulia; Rønningen, Kjersti S.

In: Pediatric Diabetes, Vol. 18, No. 2, 01.03.2017, p. 111-119.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study

AU - Jørgenrud, Benedicte

AU - Stene, Lars C.

AU - Tapia, German

AU - Bøås, Håkon

AU - Pepaj, Milaim

AU - Berg, Jens P.

AU - Thorsby, Per M.

AU - Orešič, Matej

AU - Hyötyläinen, Tuulia

AU - Rønningen, Kjersti S.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - AIMS: The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes.METHOD: Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites.RESULTS: Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age.CONCLUSIONS: Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.

AB - AIMS: The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes.METHOD: Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites.RESULTS: Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age.CONCLUSIONS: Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.

KW - Infant Nutritional Physiological Phenomena

KW - Blood Chemical Analysis

KW - Humans

KW - Islets of Langerhans/immunology

KW - Risk Factors

KW - Breast Feeding

KW - Child, Preschool

KW - Metabolome

KW - Infant

KW - Male

KW - Case-Control Studies

KW - Norway

KW - Diabetes Mellitus, Type 1/etiology

KW - Female

KW - Child

KW - Longitudinal Studies

KW - Infant, Newborn

KW - Feeding Behavior/physiology

UR - http://www.scopus.com/inward/record.url?scp=84955499390&partnerID=8YFLogxK

U2 - 10.1111/pedi.12360

DO - 10.1111/pedi.12360

M3 - Article

C2 - 26791677

AN - SCOPUS:84955499390

VL - 18

SP - 111

EP - 119

JO - Pediatric Diabetes

JF - Pediatric Diabetes

SN - 1399-543X

IS - 2

ER -