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 Peterson Lowe, Boyd E Metzger, Christopher B. Newgard, Denise M Scholtens, William L Lowe Jr*, the HAPO Study Cooperative Research Group for the HAPO Study Cooperative Research Group

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)518-530
Number of pages13
JournalDiabetologia
Volume60
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Metabolome
Insulin Resistance
Mothers
Lipids
Adiposity
Parturition
Fasting
Carbohydrates
Amino Acids
Branched Chain Amino Acids
Acids
Metabolomics
Pregnancy Outcome
Glucose Tolerance Test
Hyperglycemia
Gestational Age
Obesity
Outcome Assessment (Health Care)

Keywords

  • Fetal growth
  • Maternal BMI
  • Maternal insulin resistance
  • Maternal metabolism
  • Pregnancy

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Sandler, V., Reisetter, A. C., Bain, J. R., Muehlbauer, M. J., Nodzenski, M., Stevens, R. D., ... for the HAPO Study Cooperative Research Group, T. HAPO. S. C. R. G. (2017). Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes. Diabetologia, 60(3), 518-530. https://doi.org/10.1007/s00125-016-4182-2
Sandler, Victoria ; Reisetter, Anna C. ; Bain, James R. ; Muehlbauer, Michael J. ; Nodzenski, Michael ; Stevens, Robert D. ; Ilkayeva, Olga ; Lowe, Lynn Peterson ; Metzger, Boyd E ; Newgard, Christopher B. ; Scholtens, Denise M ; Lowe Jr, William L ; for the HAPO Study Cooperative Research Group, the HAPO Study Cooperative Research Group. / Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes. In: Diabetologia. 2017 ; Vol. 60, No. 3. pp. 518-530.
@article{673e9dce54334c87b9823cf6837e58aa,
title = "Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes",
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",
author = "Victoria Sandler and Reisetter, {Anna C.} and Bain, {James R.} and Muehlbauer, {Michael J.} and Michael Nodzenski and Stevens, {Robert D.} and Olga Ilkayeva and Lowe, {Lynn Peterson} and Metzger, {Boyd E} and Newgard, {Christopher B.} and Scholtens, {Denise M} and {Lowe Jr}, {William L} and {for the HAPO Study Cooperative Research Group}, {the HAPO Study Cooperative Research Group}",
year = "2017",
month = "3",
day = "1",
doi = "10.1007/s00125-016-4182-2",
language = "English (US)",
volume = "60",
pages = "518--530",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "3",

}

Sandler, V, Reisetter, AC, Bain, JR, Muehlbauer, MJ, Nodzenski, M, Stevens, RD, Ilkayeva, O, Lowe, LP, Metzger, BE, Newgard, CB, Scholtens, DM, Lowe Jr, WL & for the HAPO Study Cooperative Research Group, THAPOSCRG 2017, 'Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes', Diabetologia, vol. 60, no. 3, pp. 518-530. https://doi.org/10.1007/s00125-016-4182-2

Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes. / Sandler, Victoria; Reisetter, Anna C.; Bain, James R.; Muehlbauer, Michael J.; Nodzenski, Michael; Stevens, Robert D.; Ilkayeva, Olga; Lowe, Lynn Peterson; Metzger, Boyd E; Newgard, Christopher B.; Scholtens, Denise M; Lowe Jr, William L; for the HAPO Study Cooperative Research Group, the HAPO Study Cooperative Research Group.

In: Diabetologia, Vol. 60, No. 3, 01.03.2017, p. 518-530.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes

AU - Sandler, Victoria

AU - Reisetter, Anna C.

AU - Bain, James R.

AU - Muehlbauer, Michael J.

AU - Nodzenski, Michael

AU - Stevens, Robert D.

AU - Ilkayeva, Olga

AU - Lowe, Lynn Peterson

AU - Metzger, Boyd E

AU - Newgard, Christopher B.

AU - Scholtens, Denise M

AU - Lowe Jr, William L

AU - for the HAPO Study Cooperative Research Group, the HAPO Study Cooperative Research Group

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - Fetal growth

KW - Maternal BMI

KW - Maternal insulin resistance

KW - Maternal metabolism

KW - Pregnancy

UR - http://www.scopus.com/inward/record.url?scp=85006154152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006154152&partnerID=8YFLogxK

U2 - 10.1007/s00125-016-4182-2

DO - 10.1007/s00125-016-4182-2

M3 - Article

VL - 60

SP - 518

EP - 530

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 3

ER -

Sandler V, Reisetter AC, Bain JR, Muehlbauer MJ, Nodzenski M, Stevens RD et al. Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes. Diabetologia. 2017 Mar 1;60(3):518-530. https://doi.org/10.1007/s00125-016-4182-2