Metabolomics reveals broad-scale metabolic perturbations in hyperglycemic mothers during pregnancy

Denise M Scholtens*, Michael J. Muehlbauer, Natalie R. Daya, Robert D. Stevens, Alan Richard Dyer, Lynn Peterson Lowe, Boyd E Metzger, Christopher B. Newgard, James R. Bain, William L Lowe Jr

*Corresponding author for this work

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Objective To characterize metabolites across the range of maternal glucose by comparing metabolomic profiles of mothers with high and low fasting plasma glucose (FPG). Research Design And Methods We compared fasting serum from an oral glucose tolerance test at ̃28 weeks' gestation from 67 Northern European ancestry mothers from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study with high (90th percentile) FPG with 50 mothers with low (10th percentile) FPG but comparable BMI. Metabolic data from biochemical analyses of conventional clinical metabolites, targeted mass spectrometry (MS)-based measurement of amino acids, and nontargeted gas chromatography/MS were subjected to per-metabolite analyses and collective pathway analyses using Unipathway annotation. Results High-FPG mothers had a metabolic profile consistent with insulin resistance including higher triglycerides, 3-hydroxybutyrate, and amino acids including alanine, proline, and branched-chain amino acids (false discovery rate [FDR]- adjusted P 0.05). Lower 1,5-anhydroglucitol in high-FPG mothers suggested recent hyperglycemic excursions (FDR-adjusted P 0.05). Pathway analyses indicated differences in amino acid degradation pathways for the two groups (FDR-adjusted P 0.05), consistent with population-based findings in nonpregnant populations. Exploratory analyses with newborn outcomes indicated positive associations for maternal triglycerides with neonatal sum of skinfolds and cord C-peptide and a negative associationbetweenmaternal glycine andcord C-peptide (P 0.05). Conclusions Metabolomics reveals perturbations in metabolism of major macronutrients and amino acid degradation pathways in high- versus low-FPG mothers.

Original languageEnglish (US)
Pages (from-to)158-166
Number of pages9
JournalDiabetes Care
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2014

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Metabolomics
Fasting
Glucose
Pregnancy
Amino Acids
C-Peptide
Triglycerides
Mothers
Branched Chain Amino Acids
3-Hydroxybutyric Acid
Metabolome
Pregnancy Outcome
Glucose Tolerance Test
Proline
Hyperglycemia
Alanine
Gas Chromatography-Mass Spectrometry
Glycine
Population
Insulin Resistance

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Scholtens, Denise M ; Muehlbauer, Michael J. ; Daya, Natalie R. ; Stevens, Robert D. ; Dyer, Alan Richard ; Lowe, Lynn Peterson ; Metzger, Boyd E ; Newgard, Christopher B. ; Bain, James R. ; Lowe Jr, William L. / Metabolomics reveals broad-scale metabolic perturbations in hyperglycemic mothers during pregnancy. In: Diabetes Care. 2014 ; Vol. 37, No. 1. pp. 158-166.
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abstract = "Objective To characterize metabolites across the range of maternal glucose by comparing metabolomic profiles of mothers with high and low fasting plasma glucose (FPG). Research Design And Methods We compared fasting serum from an oral glucose tolerance test at ̃28 weeks' gestation from 67 Northern European ancestry mothers from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study with high (90th percentile) FPG with 50 mothers with low (10th percentile) FPG but comparable BMI. Metabolic data from biochemical analyses of conventional clinical metabolites, targeted mass spectrometry (MS)-based measurement of amino acids, and nontargeted gas chromatography/MS were subjected to per-metabolite analyses and collective pathway analyses using Unipathway annotation. Results High-FPG mothers had a metabolic profile consistent with insulin resistance including higher triglycerides, 3-hydroxybutyrate, and amino acids including alanine, proline, and branched-chain amino acids (false discovery rate [FDR]- adjusted P 0.05). Lower 1,5-anhydroglucitol in high-FPG mothers suggested recent hyperglycemic excursions (FDR-adjusted P 0.05). Pathway analyses indicated differences in amino acid degradation pathways for the two groups (FDR-adjusted P 0.05), consistent with population-based findings in nonpregnant populations. Exploratory analyses with newborn outcomes indicated positive associations for maternal triglycerides with neonatal sum of skinfolds and cord C-peptide and a negative associationbetweenmaternal glycine andcord C-peptide (P 0.05). Conclusions Metabolomics reveals perturbations in metabolism of major macronutrients and amino acid degradation pathways in high- versus low-FPG mothers.",
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Metabolomics reveals broad-scale metabolic perturbations in hyperglycemic mothers during pregnancy. / Scholtens, Denise M; Muehlbauer, Michael J.; Daya, Natalie R.; Stevens, Robert D.; Dyer, Alan Richard; Lowe, Lynn Peterson; Metzger, Boyd E; Newgard, Christopher B.; Bain, James R.; Lowe Jr, William L.

In: Diabetes Care, Vol. 37, No. 1, 01.01.2014, p. 158-166.

Research output: Contribution to journalArticle

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AU - Scholtens, Denise M

AU - Muehlbauer, Michael J.

AU - Daya, Natalie R.

AU - Stevens, Robert D.

AU - Dyer, Alan Richard

AU - Lowe, Lynn Peterson

AU - Metzger, Boyd E

AU - Newgard, Christopher B.

AU - Bain, James R.

AU - Lowe Jr, William L

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N2 - Objective To characterize metabolites across the range of maternal glucose by comparing metabolomic profiles of mothers with high and low fasting plasma glucose (FPG). Research Design And Methods We compared fasting serum from an oral glucose tolerance test at ̃28 weeks' gestation from 67 Northern European ancestry mothers from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study with high (90th percentile) FPG with 50 mothers with low (10th percentile) FPG but comparable BMI. Metabolic data from biochemical analyses of conventional clinical metabolites, targeted mass spectrometry (MS)-based measurement of amino acids, and nontargeted gas chromatography/MS were subjected to per-metabolite analyses and collective pathway analyses using Unipathway annotation. Results High-FPG mothers had a metabolic profile consistent with insulin resistance including higher triglycerides, 3-hydroxybutyrate, and amino acids including alanine, proline, and branched-chain amino acids (false discovery rate [FDR]- adjusted P 0.05). Lower 1,5-anhydroglucitol in high-FPG mothers suggested recent hyperglycemic excursions (FDR-adjusted P 0.05). Pathway analyses indicated differences in amino acid degradation pathways for the two groups (FDR-adjusted P 0.05), consistent with population-based findings in nonpregnant populations. Exploratory analyses with newborn outcomes indicated positive associations for maternal triglycerides with neonatal sum of skinfolds and cord C-peptide and a negative associationbetweenmaternal glycine andcord C-peptide (P 0.05). Conclusions Metabolomics reveals perturbations in metabolism of major macronutrients and amino acid degradation pathways in high- versus low-FPG mothers.

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