Diabetologia

, Volume 60, Issue 3, pp 518–530

Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes

  • Victoria Sandler
  • Anna C. Reisetter
  • James R. Bain
  • Michael J. Muehlbauer
  • Michael Nodzenski
  • Robert D. Stevens
  • Olga Ilkayeva
  • Lynn P. Lowe
  • Boyd E. Metzger
  • Christopher B. Newgard
  • Denise M. Scholtens
  • William L. LoweJr
  • for the HAPO Study Cooperative Research Group
Article

DOI: 10.1007/s00125-016-4182-2

Cite this article as:
Sandler, V., Reisetter, A.C., Bain, J.R. et al. Diabetologia (2017) 60: 518. doi:10.1007/s00125-016-4182-2

Abstract

Aims/hypothesis

Maternal obesity increases the risk for large-for-gestational-age birth and excess newborn adiposity, which are associated with adverse long-term metabolic outcomes in offspring, probably due to effects mediated through the intrauterine environment. We aimed to characterise the maternal metabolic milieu associated with maternal BMI and its relationship to newborn birthweight and adiposity.

Methods

Fasting and 1 h serum samples were collected from 400 European-ancestry mothers in the Hyperglycaemia and Adverse Pregnancy Outcome Study who underwent an OGTT at ∼28 weeks gestation and whose offspring had anthropometric measurements at birth. Metabolomics assays were performed using biochemical analyses of conventional clinical metabolites, targeted MS-based measurement of amino acids and acylcarnitines and non-targeted GC/MS.

Results

Per-metabolite analyses demonstrated broad associations with maternal BMI at fasting and 1 h for lipids, amino acids and their metabolites together with carbohydrates and organic acids. Similar metabolite classes were associated with insulin resistance with unique associations including branched-chain amino acids. Pathway analyses indicated overlapping and unique associations with maternal BMI and insulin resistance. Network analyses demonstrated collective associations of maternal metabolite subnetworks with maternal BMI and newborn size and adiposity, including communities of acylcarnitines, lipids and related metabolites, and carbohydrates and organic acids. Random forest analyses demonstrated contribution of lipids and lipid-related metabolites to the association of maternal BMI with newborn outcomes.

Conclusions/interpretation

Higher maternal BMI and insulin resistance are associated with broad-based changes in maternal metabolites, with lipids and lipid-related metabolites accounting, in part, for the association of maternal BMI with newborn size at birth.

Keywords

Fetal growth Maternal BMI Maternal insulin resistance Maternal metabolism Pregnancy 

Abbreviations

BCAA

Branched-chain amino acid

BW

Birthweight

FDR

False discovery rate

FPG

Fasting plasma glucose

GDM

Gestational diabetes mellitus

HAPO

Hyperglycaemia and Adverse Pregnancy Outcome

QC

Quality control

RTL

Retention-time-locked

SSF

Sum of skinfolds

Supplementary material

125_2016_4182_MOESM1_ESM.pdf (406 kb)
ESM(PDF 405 kb)

Funding information

Funder NameGrant NumberFunding Note
National Institute of Diabetes and Digestive and Kidney Diseases
  • R01DK095963
National Institute of Child Health and Human Development
  • R01-HD34243

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Victoria Sandler
    • 1
  • Anna C. Reisetter
    • 1
  • James R. Bain
    • 2
    • 3
    • 4
  • Michael J. Muehlbauer
    • 2
    • 3
    • 4
  • Michael Nodzenski
    • 1
  • Robert D. Stevens
    • 2
    • 3
    • 4
  • Olga Ilkayeva
    • 2
    • 3
    • 4
  • Lynn P. Lowe
    • 1
  • Boyd E. Metzger
    • 1
  • Christopher B. Newgard
    • 2
    • 3
    • 4
  • Denise M. Scholtens
    • 1
  • William L. LoweJr
    • 1
  • for the HAPO Study Cooperative Research Group
  1. 1.Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Sarah W. Stedman Nutrition and Metabolism CenterDuke University Medical CenterDurhamUSA
  3. 3.Duke Molecular Physiology InstituteDurhamUSA
  4. 4.Duke University School of MedicineDurhamUSA

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