TY - JOUR
T1 - Metabolic networks and metabolites underlie associations between maternal glucose during pregnancy and newborn size at birth
AU - Scholtens, Denise M.
AU - Bain, James R.
AU - Reisetter, Anna C.
AU - Muehlbauer, Michael J.
AU - Nodzenski, Michael
AU - Stevens, Robert D.
AU - Ilkayeva, Olga
AU - Lowe, Lynn P.
AU - Metzger, Boyd E.
AU - Newgard, Christopher B.
AU - Lowe, William L.
N1 - Funding Information:
This study was funded by National Institute of Diabetes and Digestive and Kidney Diseases (grant R01-DK-095963) by the National Institute of Child Health and Human Development (grants R01-HD-34242 and R01-HD-34243).
Publisher Copyright:
© 2016 by the American Diabetes Association.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
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U2 - 10.2337/db15-1748
DO - 10.2337/db15-1748
M3 - Article
C2 - 27207545
AN - SCOPUS:84975840947
SN - 0012-1797
VL - 65
SP - 2039
EP - 2050
JO - Diabetes
JF - Diabetes
IS - 7
ER -