Cited by 302Gestational Diabetes Research and ManagementBirth, Development, and HealthObesity, Physical Activity, Diet

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Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study

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on behalf of the HAPO Follow-up Study Cooperative Research Group, Lowe, William L., Lowe, Lynn P., Kuang, Alan, Catalano, Patrick M., Nodzenski, Michael, Talbot, Octavious, Tam, Wing-Hung, Sacks, David A., McCance, David, Linder, Barbara, Lebenthal, Yael, Lawrence, Jean M., Lashley, Michele, Josefson, Jami L., Hamilton, Jill, Deerochanawong, Chaicharn, Clayton, Peter, Brickman, Wendy J., Dyer, Alan R., Scholtens, Denise M., Metzger, Boyd E.·2019·Diabetologia

DOI 10.1007/s00125-018-4809-6PMC PMC6421132

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Abstract

Aims/hypothesisMaternal type 2 diabetes during pregnancy and gestational diabetes are associated with childhood adiposity; however, associations of lower maternal glucose levels during pregnancy with childhood adiposity, independent of maternal BMI, remain less clear. The objective was to examine associations of maternal glucose levels during pregnancy with childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.MethodsThe HAPO Study was an observational epidemiological international multi-ethnic investigation that established strong associations of glucose levels during pregnancy with multiple adverse perinatal outcomes. The HAPO Follow-up Study (HAPO FUS) included 4832 children from ten HAPO centres whose mothers had a 75 g OGTT at ~28 weeks gestation 10–14 years earlier, with glucose values blinded to participants and clinical caregivers. The primary outcome was child adiposity, including: (1) being overweight/obese according to sex- and age-specific cut-offs based on the International Obesity Task Force (IOTF) criteria; (2) IOTF-defined obesity only; and (3) measurements >85th percentile for sum of skinfolds, waist circumference and per cent body fat. Primary predictors were maternal OGTT and HbA1c values during pregnancy.ResultsFully adjusted models that included maternal BMI at pregnancy OGTT indicated positive associations between maternal glucose predictors and child adiposity outcomes. For one SD difference in pregnancy glucose and HbA1c measures, ORs for each child adiposity outcome were in the range of 1.05–1.16 for maternal fasting glucose, 1.11–1.19 for 1 h glucose, 1.09–1.21 for 2 h glucose and 1.12–1.21 for HbA1c. Associations were significant, except for associations of maternal fasting glucose with offspring being overweight/obese or having waist circumference >85th percentile. Linearity was confirmed in all adjusted models. Exploratory sex-specific analyses indicated generally consistent associations for boys and girls.Conclusions/interpretationExposure to higher levels of glucose in utero is independently associated with childhood adiposity, including being overweight/obese, obesity, skinfold thickness, per cent body fat and waist circumference. Glucose levels less than those diagnostic of diabetes are associated with greater childhood adiposity; this may have implications for long-term metabolic health.

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Additional file 3 of Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy
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Additional file 1 of Timing of gestational diabetes diagnosis, gestational weight gains and offspring growth trajectory: a prospective birth cohort study
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Additional file 3 of DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Salama, O. E., Hizon, N. A., VECCHIO, M. D., Kolsun, K. P., Fonseca, M. A., Lin, D. T. S., Urtatiz, O., MacIsaac, J. L., Kobor, M. S., Sellers, E. A. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26719815
Additional file 1 of Impact of preconception and antenatal supplementation with myo-inositol, probiotics, and micronutrients on offspring BMI and weight gain over the first 2 years
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Additional file 7 of Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy
Xue, C., Xie, Q., Zhang, C., Hu, Y., Song, X., Jia, Y., Shi, X., Chen, Y., Liu, Y., Zhao, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454692
Additional file 2 of Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy
Xue, C., Xie, Q., Zhang, C., Hu, Y., Song, X., Jia, Y., Shi, X., Chen, Y., Liu, Y., Zhao, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454677
Additional file 5 of DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Salama, O. E., Hizon, N. A., VECCHIO, M. D., Kolsun, K. P., Fonseca, M. A., Lin, D. T. S., Urtatiz, O., MacIsaac, J. L., Kobor, M. S., Sellers, E. A. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26719821
Additional file 6 of DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Salama, O. E., Hizon, N. A., VECCHIO, M. D., Kolsun, K. P., Fonseca, M. A., Lin, D. T. S., Urtatiz, O., MacIsaac, J. L., Kobor, M. S., Sellers, E. A. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26719824
Additional file 8 of DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Salama, O. E., Hizon, N. A., VECCHIO, M. D., Kolsun, K. P., Fonseca, M. A., Lin, D. T. S., Urtatiz, O., MacIsaac, J. L., Kobor, M. S., Sellers, E. A. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26719830
Additional file 1 of Subsidized gestational diabetes mellitus screening and management program in rural China: a pragmatic multicenter, randomized controlled trial
Xu, T., Xia, Q., Lai, X., He, K., Fan, D., Ma, L., & Fang, H. (2024) · Figshare · doi:10.6084/m9.figshare.25347104
Additional file 7 of DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Salama, O. E., Hizon, N. A., VECCHIO, M. D., Kolsun, K. P., Fonseca, M. A., Lin, D. T. S., Urtatiz, O., MacIsaac, J. L., Kobor, M. S., Sellers, E. A. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26719827
Additional file 4 of DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Salama, O. E., Hizon, N. A., VECCHIO, M. D., Kolsun, K. P., Fonseca, M. A., Lin, D. T. S., Urtatiz, O., MacIsaac, J. L., Kobor, M. S., Sellers, E. A. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26719818
Additional file 6 of Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy
Xue, C., Xie, Q., Zhang, C., Hu, Y., Song, X., Jia, Y., Shi, X., Chen, Y., Liu, Y., Zhao, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454689
Additional file 2 of DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Salama, O. E., Hizon, N. A., VECCHIO, M. D., Kolsun, K. P., Fonseca, M. A., Lin, D. T. S., Urtatiz, O., MacIsaac, J. L., Kobor, M. S., Sellers, E. A. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25815631
Additional file 5 of Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy
Xue, C., Xie, Q., Zhang, C., Hu, Y., Song, X., Jia, Y., Shi, X., Chen, Y., Liu, Y., Zhao, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454686
Additional file 1 of Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy
Xue, C., Xie, Q., Zhang, C., Hu, Y., Song, X., Jia, Y., Shi, X., Chen, Y., Liu, Y., Zhao, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454674
Additional file 4 of Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy
Xue, C., Xie, Q., Zhang, C., Hu, Y., Song, X., Jia, Y., Shi, X., Chen, Y., Liu, Y., Zhao, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20454683
Additional file 2 of Impact of preconception and antenatal supplementation with myo-inositol, probiotics, and micronutrients on offspring BMI and weight gain over the first 2 years
Lyons‐Reid, J., Derraik, J. G., Kenealy, T. W., Albert, B. B., Ramos Nieves, J. M., Monnard, C. R., Titcombe, P., Nield, H., Barton, S. J., El-Heis, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25107877
Additional file 1 of DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Salama, O. E., Hizon, N. A., VECCHIO, M. D., Kolsun, K. P., Fonseca, M. A., Lin, D. T. S., Urtatiz, O., MacIsaac, J. L., Kobor, M. S., Sellers, E. A. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25815056
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Zeng, Y., Yu, J., Ren, Y., Ren, J. L., Chen, H., Zhang, Q., & XIAO, X. (2025) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-025-08294-5
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Authors: on behalf of the HAPO Follow-up Study Cooperative Research Group, Lowe, W. L., Lowe, L. P., Kuang, A., Catalano, P. M., Nodzenski, M., Talbot, O., Tam, W.-H., Sacks, D. A., McCance, D., Linder, B., Lebenthal, Y., Lawrence, J. M., Lashley, M., Josefson, J. L., Hamilton, J., Deerochanawong, C., Clayton, P., Brickman, W. J., Dyer, A. R., Scholtens, D. M., & Metzger, B. E.
Affiliations: Northwestern University (US)
MetroHealth Medical Center (US)
Chinese University of Hong Kong (HK)
Kaiser Permanente (US)
Royal Victoria Hospital (GB)
National Institutes of Health (US)
Tel Aviv University (IL)
University of Toronto (CA)
Rajavithi Hospital (TH)
Manchester Academic Health Science Centre (GB)
Corresponding author: Metzger, Boyd E.
ORCID: Lowe, William L.
Lowe, Lynn P.
Kuang, Alan
Catalano, Patrick M.
Nodzenski, Michael
Talbot, Octavious
Tam, Wing-Hung
Sacks, David A.
Lebenthal, Yael
Lawrence, Jean M.
Josefson, Jami L.
Hamilton, Jill
Deerochanawong, Chaicharn
Clayton, Peter
Dyer, Alan R.
Scholtens, Denise M.
Metzger, Boyd E.
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2019-01-15
Volume: 62
Issue: 4
Pages: 598-610
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-018-4809-6
PMC: PMC6421132
OpenAlex: W2911007152
Semantic Scholar: 2e46697541db330189cda46dc419697dbff59a5c
Cited by: 294
References: 44
Citations by year: 2026: 28 · 2025: 38 · 2024: 54 · 2023: 44 · 2022: 58 · 2021: 29 · 2020: 32 · 2019: 10
FWCI: 35.06
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Diabetologia (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders: Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Center for Advancing Translational Sciences (UL1TR001422)
National Institute of Diabetes and Digestive and Kidney Diseases (1U01DK094830)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
Keywords: childhood adiposity, hyperglycemia in pregnancy, maternal type 2 diabetes, gestational diabetes mellitus, HbA1c, oral glucose tolerance test, offspring obesity, skinfold thickness, waist circumference, body fat percentage
MeSH terms: Adult, Blood Glucose, Child, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Hyperglycemia, Male, Maternal Age, Pregnancy, Pregnancy Complications, Pregnancy in Diabetics, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Body Mass Index, Diabetes, Gestational, Adiposity, Overweight, Waist Circumference, Pediatric Obesity

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Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study

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