Underlying dyslipidemia postpartum in women with a recent GDM pregnancy who develop Type 2 diabetes

  1. Mi Lai
  2. Dana Al Rijjal
  3. Hannes L Röst  Is a corresponding author
  4. Feihan F Dai  Is a corresponding author
  5. Erica P Gunderson  Is a corresponding author
  6. Michael B Wheeler  Is a corresponding author
  1. University of Toronto, Canada
  2. Kaiser Permanente Northern California, United States

Abstract

Approximately 35% of women with Gestational Diabetes (GDM) progress to Type2 Diabetes (T2D) within 10 years. However, links between GDM and T2D are not well understood. We used a well-characterised GDM prospective cohort of 1,035 women following up to 8 years postpartum. Lipidomics profiling covering >1000 lipids, was performed on fasting plasma samples from participants 6-9week postpartum (171 incident T2D vs. 179 controls). We discovered 311 lipids positively and 70 lipids negatively associated with T2D risk. The upregulation of glycerolipid metabolism involving triacylglycerol and diacylglycerol biosynthesis suggested activated lipid storage before diabetes onset. In contrast, decreased sphingomyelines, hexosylceramide and lactosylceramide indicated impaired sphingolipid metabolism. Additionally, a lipid signature was identified to effectively predict future diabetes risk. These findings demonstrate an underlying dyslipidemia during the early postpartum in those GDM women who progress to T2D and suggest endogenous lipogenesis may be a driving force for future diabetes onset.

Data availability

Lipidomic data have been deposited in Harvard Dataverse: https://doi.org/10.7910/DVN/KUDDSF.Source data files have been provided for Figures 2, 3 , 4 and 6 as supporting files.

The following data sets were generated
    1. Michael Wheeler
    (2020) SWIFT lipidomics data
    Harvard Dataverse, 10.7910/DVN/KUDDSF.

Article and author information

Author details

  1. Mi Lai

    Department of Physiology, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  2. Dana Al Rijjal

    Department of Physiology, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  3. Hannes L Röst

    Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, Canada
    For correspondence
    hannes.rost@utoronto.ca
    Competing interests
    No competing interests declared.
  4. Feihan F Dai

    Department of Physiology, University of Toronto, Toronto, Canada
    For correspondence
    f.dai@utoronto.ca
    Competing interests
    No competing interests declared.
  5. Erica P Gunderson

    Division of Research, Kaiser Permanente Northern California, Oakland, United States
    For correspondence
    Erica.Gunderson@kp.org
    Competing interests
    Erica P Gunderson, Erica P. Gunderson is affiliated with Kaiser Permanente. EPG has declared a research grant from Janssen Pharmaceuticals Company. EPG has no other financial interests to declare..
  6. Michael B Wheeler

    Physiology, University of Toronto, Toronto, Canada
    For correspondence
    michael.wheeler@utoronto.ca
    Competing interests
    Michael B Wheeler, MBW has declared a research grant from Janssen Pharmaceuticals Company.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7480-7267

Funding

Canadian Institutes of Health Research (FRN 143219)

  • Michael B Wheeler

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD050625)

  • Erica P Gunderson

The National Institute of Digestive, Diabetes and Kidney Disease (R01 DK118409)

  • Erica P Gunderson

Janssen Pharmaceuticals (430086739)

  • Erica P Gunderson
  • Michael B Wheeler

Banting and Best Diabetes Centre, University of Toronto (postdoctoral fellowships)

  • Mi Lai

Ontario Graduate Scholarship (Graduate Student Fellowship)

  • Dana Al Rijjal

Banting and Best Diabetes Centre, University of Toronto (Graduate Student Fellowship)

  • Dana Al Rijjal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study design and all procedures were approved by the Kaiser Permanente Northern California Institutional Review Board (protocol numbers #CN-04EGund-03-H and #1279812-10) and Office of Research Ethics at University of Toronto (protocol number #38188). All participants gave written informed consent before taking part in the research exams.

Copyright

© 2020, Lai et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Mi Lai
  2. Dana Al Rijjal
  3. Hannes L Röst
  4. Feihan F Dai
  5. Erica P Gunderson
  6. Michael B Wheeler
(2020)
Underlying dyslipidemia postpartum in women with a recent GDM pregnancy who develop Type 2 diabetes
eLife 9:e59153.
https://doi.org/10.7554/eLife.59153

Share this article

https://doi.org/10.7554/eLife.59153

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