Joint Associations of Maternal Gestational Diabetes and Hypertensive Disorders of Pregnancy With Overweight in Offspring

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Abstract

Objectives: Either maternal gestational diabetes mellitus (GDM) or hypertensive disorder of pregnancy (HDP) is associated with an increased risk of obesity in the offspring. However, their joint associations with obesity in offspring remain unclear. We investigated the joint associations of maternal GDM and HDP with childhood overweight in offspring.

Methods: We performed a large study in 1967 mother-child pairs. Maternal GDM was diagnosed according to the 1999 World Health Organization (WHO) criteria. HDP was defined as self-reported doctor-diagnosed hypertension or treatment of hypertension (including gestational hypertension, preeclampsia, sever preeclampsia or eclampsia) after 20 weeks of gestation on the questionnaire. Body mass index (BMI) for age Z-score and childhood overweight were evaluated according to WHO growth reference. We used the general linear models to compare children's Z score for BMI and logistic regression models to estimate odds ratios of childhood overweight according to maternal different status of GDM and HDP.

Results: Offspring of mothers with both GDM and HDP had a higher BMI for age Z-score (0.63 vs. 0.03, P < 0.001) than children born to normotensive and normoglycemic pregnancy. After adjustment for maternal and children's major confounding factors, joint GDM and HDP were associated with increased odds ratios of offspring's overweight compared with normotensive and normoglycemic pregnancy (2.97, 95% confidence intervals [CIs] 1.65–5.34) and GDM alone (2.06, 95% CIs 1.20–3.54), respectively. After additional adjustment for maternal pre-pregnancy BMI and gestational weight gain, joint maternal GDM, and HDP was still associated with an increased risk of offspring's overweight compared with the maternal normotensive, and normoglycemic group but became to have a borderline increased risk compared with the maternal GDM alone group.

Conclusions: Maternal GDM alone or joint GDM and HDP were associated with increased ratios of offspring's overweight.

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Most cited references 30

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Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia.

Teresa A. Hillier, Kathryn L Pedula, Mark Schmidt … (2007)

The purpose of this study was to determine how the range of measured maternal glycemia in pregnancy relates to risk of obesity in childhood. Universal gestational diabetes mellitus (GDM) screening (a 50-g glucose challenge test [GCT]) was performed in two regions (Northwest and Hawaii) of a large diverse HMO during 1995-2000, and GDM was diagnosed/treated using a 3-h 100-g oral glucose tolerance test (OGTT) and National Diabetes Data Group (NDDG) criteria. Measured weight in offspring (n = 9,439) was ascertained 5-7 years later to calculate sex-specific weight-for-age percentiles using U.S. norms (1963-1994 standard) and then classified by maternal positive GCT (1 h >or= 7.8 mmol/l) and OGTT results (1 or >or=2 of the 4 time points abnormal: fasting, 1 h, 2 h, or 3 h by Carpenter and Coustan and NDDG criteria). There was a positive trend for increasing childhood obesity at age 5-7 years (P < 0.0001; 85th and 95th percentiles) across the range of increasing maternal glucose screen values, which remained after adjustment for potential confounders including maternal weight gain, maternal age, parity, ethnicity, and birth weight. The risk of childhood obesity in offspring of mothers with GDM by NDDG criteria (treated) was attenuated compared with the risks for the groups with lesser degrees of hyperglycemia (untreated). The relationships were similar among Caucasians and non-Caucasians. Stratification by birth weight also revealed these effects in children of normal birth weight (

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Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes.

Jeannet Lauenborg, Torben Hansen, Elisabeth Mathiesen … (2009)

In animal studies, exposure to intrauterine hyperglycemia increases the risk of cardiovascular disease through only partly understood epigenetic mechanisms. Human long-term follow-up studies on the same topic are few. The aim was to study the risk of overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus (GDM) or type 1 diabetes, and additionally to study associations between estimates of maternal hyperglycemia and outcome in the offspring. We conducted a follow-up study of 1066 primarily Caucasian women aged 18-27 yr in the Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark. Offspring of women with diet-treated GDM (n = 168) and an unexposed reference group (n = 141) participated, as well as offspring of women with type 1 diabetes (n = 160) and offspring from the background population representing an unexposed reference group (n = 128). The follow-up rate was 56% (597 of 1066). Women with body mass index of at least 25 kg/m(2) were considered overweight. The metabolic syndrome was determined by the International Diabetes Federation 2006 criteria. The risk of overweight was doubled in offspring of women with diet-treated GDM or type 1 diabetes compared with offspring from the background population, whereas the risk of the metabolic syndrome was 4- and 2.5-fold increased, respectively. Offspring risk of the metabolic syndrome increased significantly with increasing maternal fasting blood glucose as well as 2-h blood glucose (during oral glucose tolerance test). Adult offspring of women with diet-treated GDM or type 1 diabetes are risk groups for overweight and the metabolic syndrome. Intrauterine hyperglycemia may in addition to genetics and other factors contribute to the pathogenesis of overweight and the metabolic syndrome.

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Frequency, Immunogenetics, and Clinical Characteristics of Latent Autoimmune Diabetes in China (LADA China Study)

Zhiguang Zhou, Yufei Xiang, Linong Ji … (2013)

Adult non–insulin requiring diabetes includes latent autoimmune diabetes of adults (LADA), distinguished from type 2 diabetes by the presence of islet autoantibodies. LADA China determined the characteristics of Chinese LADA. This nationwide, multicenter, clinic-based cross-sectional study was conducted in 46 university-affiliated hospitals in 25 Chinese cities. All 4,880 ketosis-free diabetic patients ( 6 months, aged ≥30 years) had GAD antibody (GADA) and HLA-DQ genotype measured centrally with clinical data collected locally. GADA-positive subjects were classified as LADA. Of the patients, 5.9% were GADA positive with LADA. LADA showed a north-south gradient. Compared with GADA-negative type 2 diabetes, LADA patients were leaner, with lower fasting C-peptide and less metabolic syndrome. Patients with high GADA titers are phenotypically different from those with low GADA titers, while only a higher HDL distinguished the latter from those with type 2 diabetes. HLA diabetes–susceptible haplotypes were more frequent in LADA, even in those with low-titer GADA. HLA diabetes-protective haplotypes were less frequent in LADA. Our study implicates universal immunogenetic effects, with some ethnic differences, in adult-onset autoimmune diabetes. Autoantibody positivity and titer could be important for LADA risk stratification and accurate therapeutic choice in clinical practice.

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Author and article information

Contributors

Jun Lu: URI : http://loop.frontiersin.org/people/808381/overview

Jaakko Tuomilehto: URI : http://loop.frontiersin.org/people/612083/overview

Xilin Yang: URI : http://loop.frontiersin.org/people/485235/overview

Lifang Hou: URI : http://loop.frontiersin.org/people/24834/overview

Gang Hu: URI : http://loop.frontiersin.org/people/536011/overview

Journal

Journal ID (nlm-ta): Front Endocrinol (Lausanne)

Journal ID (iso-abbrev): Front Endocrinol (Lausanne)

Journal ID (publisher-id): Front. Endocrinol.

Title: Frontiers in Endocrinology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2392

Publication date (Electronic): 20 September 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 645

Affiliations

[1] ¹Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center , Baton Rouge, LA, United States

[2] ²Shanghai Business School , Shanghai, China

[3] ³Department of Endocrinology and Metabolism, Fengxian Hospital of Southern Medical University , Shanghai, China

[4] ⁴Tianjin Women's and Children's Health Center , Tianjin, China

[5] ⁵Department of Public Health, University of Helsinki , Helsinki, Finland

[6] ⁶Population Cancer Research Program, Dalhousie University , Halifax, NS, Canada

[7] ⁷Department of Epidemiology, School of Public Health, Tianjin Medical University , Tianjin, China

[8] ⁸Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , New York, NY, United States

[9] ⁹Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University , Chicago, IL, United States

Author notes

Edited by: Tim S. Nawrot, University of Hasselt, Belgium

Reviewed by: Nelly Saenen, University of Hasselt, Belgium; Michelle Plusquin, University of Hasselt, Belgium

*Correspondence: Gang Hu gang.hu@ 123456pbrc.edu

This article was submitted to Obesity, a section of the journal Frontiers in Endocrinology

†These authors have contributed equally to this work

Article

DOI: 10.3389/fendo.2019.00645

PMC ID: 6763696

SO-VID: 06beacbe-88ab-44e6-ac77-8484af3c6532

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 29 November 2018

Date accepted : 05 September 2019

Page count

Figures: 0, Tables: 3, Equations: 0, References: 43, Pages: 7, Words: 5548

Funding

Funded by: National Institutes of Health 10.13039/100000002

Funded by: National Institute of Diabetes and Digestive and Kidney Diseases 10.13039/100000062

Joint Associations of Maternal Gestational Diabetes and Hypertensive Disorders of Pregnancy With Overweight in Offspring

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Most cited references 30

Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia.

Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes.

Frequency, Immunogenetics, and Clinical Characteristics of Latent Autoimmune Diabetes in China (LADA China Study)

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