William L Lowe1, Lynn P Lowe2, Alan Kuang2, Patrick M Catalano3,4, Michael Nodzenski2, Octavious Talbot2, Wing-Hung Tam5,6, David A Sacks7, David McCance8, Barbara Linder9, Yael Lebenthal10,11, Jean M Lawrence7, Michele Lashley12, Jami L Josefson13,14, Jill Hamilton15, Chaicharn Deerochanawong16, Peter Clayton17,18, Wendy J Brickman13,14, Alan R Dyer2, Denise M Scholtens2, Boyd E Metzger19. 1. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. 2. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 3. MetroHealth Medical Center, Cleveland, OH, USA. 4. Nutrition Obesity Research Center, School of Medicine, Case Western Reserve University, Cleveland, OH, USA. 5. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China. 6. Prince of Wales Hospital, Hong Kong, China. 7. Kaiser Permanente Southern California, Pasadena, CA, USA. 8. Royal Victoria Hospital, Belfast, UK. 9. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA. 10. Schneider Children's Medical Center of Israel, Petah-Tiqva, Israel. 11. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 12. School of Clinical Medicine and Research, Queen Elizabeth Hospital, University of the West Indies, St Michael, Barbados. 13. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 14. Ann and Robert H Lurie Children's Hospital, Chicago, IL, USA. 15. The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 16. Rajavithi Hospital, Bangkok, Thailand. 17. Royal Manchester Children's Hospital, Royal Manchester University Hospitals, NHS Foundation Trust, Manchester, UK. 18. Manchester Academic Health Sciences Centre, School of Medical Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK. 19. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. bem@northwestern.edu.
Abstract
AIMS/HYPOTHESIS: Maternal 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. METHODS: The 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. RESULTS: Fully 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/ INTERPRETATION: Exposure 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.
AIMS/HYPOTHESIS: Maternal 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. METHODS: The 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. RESULTS: Fully 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/ INTERPRETATION: Exposure 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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