Journal
DIABETES CARE
Volume 37, Issue 1, Pages 158-166Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc13-0989
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Funding
- National Institute of Child Health and Human Development [R01-HD34242, R01-HD34243]
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Research Resources [M01-RR00048, M01-RR00080]
- National Institute on Aging [P30-AG028716]
- American Diabetes Association
- Friends of Prentice
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD034242, R01HD034243] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000048, M01RR000080] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P30AG028716] Funding Source: NIH RePORTER
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OBJECTIVETo 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 METHODSWe compared fasting serum from an oral glucose tolerance test at approximate to 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.RESULTSHigh-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).CONCLUSIONSMetabolomics reveals perturbations in metabolism of major macronutrients and amino acid degradation pathways in high- versus low-FPG mothers.
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