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PreprintCited by 62Gestational Diabetes Research and ManagementGrowth Hormone and Insulin-like Growth FactorsPregnancy and preeclampsia studies

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Placental RNA sequencing implicates IGFBP1 in insulin sensitivity during pregnancy and in gestational diabetes

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Hivert, Marie-France, White, Frederique, Allard, Catherine, James, Kaitlyn, Majid, Sana, Aguet, François, Ardlie, Kristin, Edlow, Andrea, Florez, Jose, Bouchard, Luigi, Jacques, Pierre-Etienne, Karumanchi, S., Powe, Camille·2023·Nature Medicine
DOI 10.21203/rs.3.rs-3464151/v1PMC PMC11186792

Preprint — published as 10.1038/s41591-024-02936-5 · Paper page

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Abstract

Reduced insulin sensitivity (or greater insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM) pathophysiology. We conducted transcriptomic profiling of 434 human placentas and identified a strong positive association between insulin-like growth factor binding protein 1 gene (IGFBP1) expression in the placenta and insulin sensitivity at ~ 26 weeks’ gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which together with high placental gene expression levels, suggests a placental source. Higher circulating IGFBP1 levels were strongly associated with greater insulin sensitivity (lesser insulin resistance) at ~ 26 weeks’ gestation in the same cohort and two additional pregnancy cohorts. In addition, low circulating IGFBP1 levels in early pregnancy predicted subsequent GDM diagnosis in two cohorts. These results implicate IGFBP1 in the glycemic physiology of pregnancy and suggest a role for placental IGFBP1 deficiency in GDM pathogenesis.

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Metadata

Authors
Hivert, M.-F., White, F., Allard, C., James, K., Majid, S., Aguet, F., Ardlie, K., Edlow, A., Florez, J., Bouchard, L., Jacques, P.-E., Karumanchi, S., & Powe, C.
Affiliations
  • Harvard University (US)
  • Universite de Sherbrooke
  • Centre de recherche du CHUS (CA)
  • Broad Institute (US)
  • Massachusetts General Hospital
  • Université de Sherbrooke (CA)
  • Cedars-Sinai Medical Center (US)
Corresponding author
Hivert, Marie-France
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2023-10-27
Volume
30
Issue
6
Pages
1689-1695
ISSN
1078-8956 (ISSN-L)
DOI
10.21203/rs.3.rs-3464151/v1
PMC
PMC11186792
OpenAlex
W4394832188
Cited by
62
References
1
Citations by year
2026: 26 · 2025: 27 · 2024: 9
FWCI
34.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Medicine (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • U.S. Department of Health and Human Services (K23DK113218, R01HD094150, NHLBI K24 HL157960)
  • American Diabetes Association (1-15-ACE-26)
  • Harvard Catalyst (UL1TR000170, UL1-TR-001102)
  • Diabète Québec (20697, MOP 115071)
  • Government of Canada (#MOP 115071, #PJT-152989)
  • National Institutes of Health (UL1TR000170, UL1TR001102)
  • Canadian Institutes of Health Research (PJT152989, MOP – 115071, 115071, 152989)
  • Fonds de Recherche du Québec - Santé (#20697)
  • National Heart, Lung, and Blood Institute (K24HL157960)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K23DK113218)
  • National Center for Advancing Translational Sciences
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD094150)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
IGFBP-1, placenta, insulin resistance, gestational diabetes mellitus, early pregnancy, insulin sensitivity, placental transcriptome, GDM risk prediction

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