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

Journal Article

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 association between maternal glycine and cord 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.

Full Text

Duke Authors

Cited Authors

  • Scholtens, DM; Muehlbauer, MJ; Daya, NR; Stevens, RD; Dyer, AR; Lowe, LP; Metzger, BE; Newgard, CB; Bain, JR; Lowe, WL; HAPO Study Cooperative Research Group,

Published Date

  • 2014

Published In

Volume / Issue

  • 37 / 1

Start / End Page

  • 158 - 166

PubMed ID

  • 23990511

Electronic International Standard Serial Number (EISSN)

  • 1935-5548

Digital Object Identifier (DOI)

  • 10.2337/dc13-0989

Language

  • eng

Conference Location

  • United States