Metabolic networks and metabolites underlie associations between maternal glucose during pregnancy and newborn size at birth

Denise M. Scholtens*, James R. Bain, Anna C. Reisetter, Michael J. Muehlbauer, Michael Nodzenski, Robert D. Stevens, Olga Ilkayeva, Lynn P. Lowe, Boyd E. Metzger, Christopher B. Newgard, William L. Lowe

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and non-targeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ∼28 weeks' gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines, and products of lipid metabolism decreased and triglycerides increased during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations, including amino acids, fatty acids, carbohydrates, and lipids, were found at 1 h. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates, and organic acids. Random forest analyses indicated an improved ability to predict newborn size outcomes by using maternal metabolomics data beyond traditional risk factors, including maternal glucose. Broad-scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity.

Original languageEnglish (US)
Pages (from-to)2039-2050
Number of pages12
JournalDiabetes
Volume65
Issue number7
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Scholtens, D. M., Bain, J. R., Reisetter, A. C., Muehlbauer, M. J., Nodzenski, M., Stevens, R. D., Ilkayeva, O., Lowe, L. P., Metzger, B. E., Newgard, C. B., & Lowe, W. L. (2016). Metabolic networks and metabolites underlie associations between maternal glucose during pregnancy and newborn size at birth. Diabetes, 65(7), 2039-2050. https://doi.org/10.2337/db15-1748