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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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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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“Children born to women with GDM have increased incidence of childhood adiposity and development of IGT in children aged 10 to 14 years compared with children born to mothers without GDM.56,57”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [56]
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“The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study 1 and subsequently follow‐up studies 2 , 3 , 4 have reported that gestational diabetes mellitus (GDM) is associated with various adverse pregnancy outcomes, which increases the mother's susceptibility to developing type 2 diabetes, and the child's susceptibility to developing obesity and impaired glucose tolerance in the future 3 , 4 , 5”
From Clinical challenges in early pregnancy in Japan: An update on gestational diabetes (2024) · cites this paper as [3]
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“In 10- to 14-year-old offspring, maternal hyperglycemia was linearly and positively correlated with increased total fat percent (measured by air displacement plethysmography), sum of skinfolds, and the incidence of obesity after adjusting for maternal BMI during pregnancy [8].”
From Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications (2022) · cites this paper as [8]
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“The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study 1 and subsequently follow‐up studies 2 , 3 , 4 have reported that gestational diabetes mellitus (GDM) is associated with various adverse pregnancy outcomes, which increases the mother's susceptibility to developing type 2 diabetes, and the child's susceptibility to developing obesity and impaired glucose tolerance in the future 3 , 4 , 5”
From Clinical challenges in early pregnancy in Japan: An update on gestational diabetes (2024) · cites this paper as [3]
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“The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study 1 and subsequently follow‐up studies 2 , 3 , 4 have reported that gestational diabetes mellitus (GDM) is associated with various adverse pregnancy outcomes, which increases the mother's susceptibility to developing type 2 diabetes, and the child's susceptibility to developing obesity and impaired glucose tolerance in the future 3 , 4 , 5”
From Clinical challenges in early pregnancy in Japan: An update on gestational diabetes (2024) · cites this paper as [3]
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Metadata
- 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
- Venue
- Diabetologia
- Published
- 2019-01-15
- Volume
- 62
- Issue
- 4
- Pages
- 598-610
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- 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
- 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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