Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Pediatrics

In utero exposure to maternal diabetes or hypertension and childhood hypothalamic gliosis

International Journal of Obesity volume 48, pages 594–597 (2024)Cite this article

Subjects

Abstract

Exposure to maternal diabetes (DM) or hypertension (HTN) during pregnancy impacts offspring metabolic health in childhood and beyond. Animal models suggest that induction of hypothalamic inflammation and gliosis in the offspring’s hypothalamus is a possible mechanism mediating this effect. We tested, in children, whether in utero exposures to maternal DM or HTN were associated with mediobasal hypothalamic (MBH) gliosis as assessed by brain magnetic resonance imaging (MRI). The study included a subsample of 306 children aged 9–11 years enrolled in the ABCD Study®; 49 were DM-exposed, 53 were HTN-exposed, and 204 (2:1 ratio) were age- and sex-matched children unexposed to DM and/or HTN in utero. We found a significant overall effect of group for the primary outcome of MBH/amygdala (AMY) T2 signal ratio (F(2,300):3.51, p = 0.03). Compared to unexposed children, MBH/AMY T2 signal ratios were significantly higher in the DM-exposed (β:0.05, p = 0.02), but not the HTN-exposed children (β:0.03, p = 0.13), findings that were limited to the MBH and independent of adiposity. We concluded that children exposed to maternal DM in utero display evidence of hypothalamic gliosis, suggesting that gestational DM may have a distinct influence on offspring’s brain development and, by extension, children’s long-term metabolic health.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: MRI-derived evidence of hypothalamic gliosis in children with in utero exposure to maternal DM.

Similar content being viewed by others

Data availability

National Institute of Mental Health Data Archive (NDA) ABCD Study Collection can be found here: https://nda.nih.gov/edit_collection.html?id=2573 Annual Release 3.0 and fast-track imaging active series were used and can be found here: https://nda.nih.gov/study.html?id=901 and through https://doi.org/10.15154/1519007. Data used in this manuscript can be accessed at https://doi.org/10.15154/1524669.

References

  1. Page KA, Romero A, Buchanan TA, Xiang AH. Gestational diabetes mellitus, maternal obesity, and adiposity in offspring. J Pediatr. 2014;164:807–10.

    Article  PubMed  Google Scholar 

  2. Alsnes IV, Vatten LJ, Fraser A, Bjørngaard JH, Rich-Edwards J, Romundstad PR, et al. Hypertension in Pregnancy and Offspring Cardiovascular Risk in Young Adulthood: Prospective and Sibling Studies in the HUNT Study (Nord-Trøndelag Health Study) in Norway. Hypertension. 2017;69:591–8.

    Article  CAS  PubMed  Google Scholar 

  3. Park S, Jang A, Bouret SG. Maternal obesity-induced endoplasmic reticulum stress causes metabolic alterations and abnormal hypothalamic development in the offspring. PLoS Biol. 2020;18:1–19.

    Article  Google Scholar 

  4. Grayson BE, Levasseur PR, Williams SM, Smith MS, Marks DL, Grove KL. Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology. 2010;151:1622–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Page KA, Luo S, Wang X, Chow T, Alves J, Buchanan TA, et al. Children exposed to maternal obesity or gestational diabetes mellitus during early fetal development have hypothalamic alterations that predict future weight gain. Diabetes Care. 2019;42:1473–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chandrasekaran S, Melhorn S, Olerich KLW, Angelo B, Chow T, Xiang A, et al. Exposure to gestational diabetes mellitus prior to 26 weeks is related to the presence of mediobasal hypothalamic gliosis in children. Diabetes. 2022;71:2552–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Schur EA, Melhorn SJ, Oh S-K, Lacy JM, Berkseth KE, Guyenet SJ, et al. Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans. Obesity (Silver Spring). 2015;23:2142–8.

    Article  CAS  PubMed  Google Scholar 

  8. Sewaybricker LE, Schur EA, Melhorn SJ, Campos BM, Askren MK, Nogueira GAS, et al. Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen-level dependent response to glucose ingestion. Pediatr Obes. 2019;14:e12486.

    Article  PubMed  Google Scholar 

  9. Thaler JP, Yi C, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122:153–62.

    Article  CAS  PubMed  Google Scholar 

  10. Sewaybricker LE, Huang A, Chandrasekaran S, Melhorn SJ, Schur EA. The Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans. Endocr Rev. 2023;44:281–96.

    Article  PubMed  Google Scholar 

  11. Garavan H, Bartsch H, Conway K, Decastro A, Goldstein RZ, Heeringa S, et al. Recruiting the ABCD sample: Design considerations and procedures. Dev Cogn Neurosci. 2018;32:16–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Casey BJ, Cannonier T, Conley MI, Cohen AO, Barch DM, Heitzeg MM, et al. The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites. Dev Cogn Neurosci. 2018;32:43–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Barch DM, Albaugh MD, Avenevoli S, Chang L, Clark DB, Glantz MD, et al. Demographic, physical and mental health assessments in the adolescent brain and cognitive development study: Rationale and description. Dev Cogn Neurosci. 2018;32:55–66.

    Article  PubMed  Google Scholar 

  14. Sewaybricker LE, Kee S, Melhorn SJ, Schur EA. Greater radiologic evidence of hypothalamic gliosis predicts adiposity gain in children at risk for obesity. Obesity (Silver Spring). 2021;29:1770–9.

    Article  PubMed  Google Scholar 

  15. Dearden L, Ozanne SE. Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis. Front Neuroendocrinol. 2015;39:3–16.

    Article  PubMed  Google Scholar 

  16. Poizat, Alexandre G, Rifai C, Al S, Riffault L, Crepin D, et al. Maternal resistin predisposes offspring to hypothalamic inflammation and body weight gain. PLoS One. 2019;14:1–15.

    Article  Google Scholar 

  17. Rosenbaum JL, Melhorn SJ, Schoen S, Webb MF, De Leon MRB, Humphreys M, et al. Evidence that hypothalamic gliosis is related to impaired glucose homeostasis in adults with obesity. Diabetes Care. 2022;45:416–24.

    Article  CAS  PubMed  Google Scholar 

  18. Kearney M, Perron J, Marc I, Weisnagel SJ, Tchernof A, Robitaille J. Association of prenatal exposure to gestational diabetes with offspring body composition and regional body fat distribution. Clin Obes. 2018;8:81–7.

    Article  CAS  PubMed  Google Scholar 

  19. Tessier DR, Ferraro ZM, Gruslin A. Role of leptin in pregnancy: consequences of maternal obesity. Placenta. 2013;34:205–11.

    Article  CAS  PubMed  Google Scholar 

  20. Qiao L, Wattez JS, Lee S, Nguyen A, Schaack J, Hay WW, et al. Adiponectin deficiency impairs maternal metabolic adaptation to pregnancy in mice. Diabetes. 2017;66:1126–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Data used in the preparation of this manuscript were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children age 9-10 and follow them over 10 years into early adulthood. The ABCD Study® is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from the fast track data release. The raw data are available at https://nda.nih.gov/edit_collection.html?id=2573. Instructions on how to create an NDA study are available at https://nda.nih.gov/training/modules/study.html. These authors appreciate the contribution of the ABCD study participants and their families to this research.

Funding

This research was supported by the National Institutes of Health (NIH) R01DK117623 (EAS), R01DK089036 (EAS), K24HL144917 (EAS), and University of Washington Nutrition and Obesity Research Center grant P30DK035816 (EAS).

Author information

Author notes

  1. These authors contributed equally: Kelsey L. W. Olerich, Leticia E. Sewaybricker.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Washington, Seattle, WA, USA

    Kelsey L. W. Olerich

  2. Department of Medicine, University of Washington, Seattle, WA, USA

    Leticia E. Sewaybricker, Sarah Kee, Susan J. Melhorn & Ellen A. Schur

  3. Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA

    Suchitra Chandrasekaran

Authors
  1. Kelsey L. W. Olerich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leticia E. Sewaybricker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah Kee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan J. Melhorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Suchitra Chandrasekaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ellen A. Schur
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LES, SC and EAS were involved in developing the design of the current study. KO, LES, SK carried out the MRI analysis. LES carried out the data analysis. KO, LES, SJM, EAS contributed to interpretation of the data. KO wrote the first draft of the manuscript. KO, LES, SK, SJM, SC, and EAS contributed to critical revision of the manuscript for important intellectual content. All authors approved the submitted version of the manuscript.

Corresponding author

Correspondence to Leticia E. Sewaybricker.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Olerich, K.L.W., Sewaybricker, L.E., Kee, S. et al. In utero exposure to maternal diabetes or hypertension and childhood hypothalamic gliosis. Int J Obes 48, 594–597 (2024). https://doi.org/10.1038/s41366-024-01463-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-024-01463-0

Search

Advanced search

Quick links