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Cited by 10Gestational Diabetes Research and ManagementEpigenetics and DNA MethylationBirth, Development, and Health

Epigenetic Age Acceleration in Mothers and Offspring 4–10 Years after a Pregnancy Complicated by Gestational Diabetes and Obesity

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Kanney, Nita, Patki, Amit, Chandler-Laney, Paula, Garvey, W. Timothy, Hidalgo, Bertha A.·2022·Metabolites
DOI 10.3390/metabo12121226PMC PMC9785326
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Abstract

A known association exists between exposure to gestational diabetes mellitus (GDM) and epigenetic age acceleration (EAA) in GDM-exposed offspring compared to those without GDM exposure. This association has not been assessed previously in mothers with pregnancies complicated by GDM. A total of 137 mother-child dyads with an index pregnancy 4–10 years before study enrollment were included. Clinical data and whole blood samples were collected and quantified to obtain DNA methylation (DNAm) estimates using the Illumina MethylEPIC 850K array in mothers and offspring. DNAm age and age acceleration were evaluated using the Horvath and Hannum clocks. Multivariable linear regression models were performed to determine the association between EAA and leptin, high-density lipoprotein cholesterol (HDL-C), fasting glucose, fasting insulin, and HOMA-IR. Mothers with a GDM and non-GDM pregnancy had strong correlations between chronological age and DNAm age (r > 0.70). Offspring of GDM mothers had moderate to strong correlations, whereas offspring of non-GDM mothers had moderate correlations between chronological age and DNAm age. Association analyses revealed a significant association between EAA and fasting insulin in offspring (FDR < 0.05), while HDL-C was the only metabolic marker significantly associated with EAA in mothers (FDR < 0.05). Mothers in the GDM group had a higher predicted epigenetic age and age acceleration than mothers in the non-GDM group. The association between EAA with elevated fasting insulin in offspring and elevated HDL-C in mothers suggests possible biomarkers that can better elucidate the effects of exposure to a GDM pregnancy and future cardiometabolic outcomes.

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  • The association between fasting insulin levels and epigenetic age acceleration was no longer significant after adjusting for offspring BMI, indicating that body weight mediates the relationship between GDM exposure and epigenetic aging.

    “However, this association was no longer significant after adjusting for offspring BMI, indicating that body weight mediates the relationship between GDM exposure and epigenetic aging [166].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [166]

    The Results (§3.3; page unavailable) report the opposite adjustment pattern: the fasting-insulin association was significant in the model including offspring BMI z-score, but was lost when BMI adjustment was removed. The paper does not conclude that body weight mediates a relationship between GDM exposure and epigenetic aging. (LLM, conf=0.87)

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  • Children exposed to GDM in utero exhibited a stronger correlation between chronological and epigenetic age compared with controls, indicating accelerated biological aging.

    “The authors observed that children exposed to GDM in utero exhibited a stronger correlation between chronological and epigenetic age compared with controls, indicating accelerated biological aging in this group.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [166]

    Results §3.2 reports stronger correlations between chronological and epigenetic age in GDM-exposed offspring than in controls for both clocks. But a stronger correlation does not establish accelerated aging: the Conclusions (§5; page not provided) state that the higher epigenetic age found in GDM mothers was not sustained in their offspring. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Analysis of metabolic biomarkers revealed a significant association between fasting insulin levels and epigenetic age acceleration.

    “Furthermore, the analysis of metabolic biomarkers revealed a significant association between fasting insulin levels and epigenetic age acceleration”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [166]

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Cited by

Sorted by citations

Authors
Kanney, N., Patki, A., Chandler-Laney, P., Garvey, W. T., & Hidalgo, B. A.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
Hidalgo, Bertha A.
ORCID
Venue
Metabolites
Publisher
MDPI AG
Published
2022-12-07
Volume
12
Issue
12
Pages
1226
ISSN
2218-1989 (ISSN-L)
DOI
10.3390/metabo12121226
PMC
PMC9785326
OpenAlex
W4311730197
Cited by
10
References
4
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 4
FWCI
2.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Metabolites (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
American Heart Association Strategically Focused Research Network on Transgenerational Obesity (17SFRN336101011)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
epigenetic age acceleration, gestational diabetes mellitus, maternal obesity, DNA methylation, epigenetic clocks, Horvath clock, Hannum clock, offspring, fasting insulin, HDL cholesterol, cardiometabolic outcomes, mother-child dyads, prenatal exposure

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