{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:48:21Z","timestamp":1787359701900,"version":"build-2736575974"},"reference-count":74,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Translational Clinical Research"},{"name":"Flagship Program on Developmental Pathways to Metabolic Disease"},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/TCR\/004-NUS\/2008"],"award-info":[{"award-number":["NMRC\/TCR\/004-NUS\/2008"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Industry Alignment Fund Pre-positioning Programme","award":["IAF-PP H17\/01\/a0\/005"],"award-info":[{"award-number":["IAF-PP H17\/01\/a0\/005"]}]},{"name":"Industry Alignment Fund Pre-positioning Programme","award":["OFLCG19may-0033"],"award-info":[{"award-number":["OFLCG19may-0033"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["NF-SI-0515-10042"],"award-info":[{"award-number":["NF-SI-0515-10042"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Global Nutrition Research Group","award":["17\/63\/154"],"award-info":[{"award-number":["17\/63\/154"]}]},{"name":"NIHR Southampton Biomedical Research Centre","award":["IS-BRC-1215-20004"],"award-info":[{"award-number":["IS-BRC-1215-20004"]}]},{"name":"European Union\u2019s Erasmus+ Programme","award":["Asia-573651-EPP-1-2016-1-DE-EPPKA2-CBHE-JP"],"award-info":[{"award-number":["Asia-573651-EPP-1-2016-1-DE-EPPKA2-CBHE-JP"]}]},{"name":"European Union\u2019s Erasmus+ Programme","award":["ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP"],"award-info":[{"award-number":["ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Antenatal hyperglycemia is associated with increased risk of future adverse health outcomes in both mother and child. Variations in offspring\u2019s epigenome can reflect the impact and response to in utero glycemic exposure, and may have different consequences for the child.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We examined possible differences in associations of basal glucose status and glucose handling during pregnancy with both clinical covariates and offspring cord tissue DNA methylation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Research Design and Methods<\/jats:title>\n                  <jats:p>This study included 830 mother-offspring dyads from the Growing Up in Singapore Towards Healthy Outcomes cohort. The fetal epigenome of umbilical cord tissue was profiled using Illumina HumanMethylation450 arrays. Associations of maternal mid-pregnancy fasting (fasting plasma glucose [FPG]) and 2-hour plasma glucose (2hPG) after a 75-g oral glucose challenge with both maternal clinical phenotypes and offspring epigenome at delivery were investigated separately.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Maternal age, prepregnancy body mass index, and blood pressure measures were associated with both FPG and 2hPG, whereas Chinese ethnicity (P = 1.9 \u00d7 10-4), maternal height (P = 1.1 \u00d7 10-4), pregnancy weight gain (P = 2.2 \u00d7 10-3), prepregnancy alcohol consumption (P = 4.6 \u00d7 10-4), and tobacco exposure (P = 1.9 \u00d7 10-3) showed significantly opposite associations between the 2 glucose measures. Most importantly, we observed a dichotomy in the effects of these glycemic indices on the offspring epigenome. Offspring born to mothers with elevated 2hPG showed global hypomethylation. CpGs most associated with the 2 measures also reflected differences in gene ontologies and had different associations with offspring birthweight.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings suggest that 2 traditionally used glycemic indices for diagnosing gestational diabetes may reflect distinctive pathophysiologies in pregnancy, and have differential impacts on the offspring\u2019s DNA methylome.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab710","type":"journal-article","created":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T12:10:37Z","timestamp":1634386237000},"page":"e1277-e1292","source":"Crossref","is-referenced-by-count":7,"title":["Dichotomy in the Impact of Elevated Maternal Glucose Levels on Neonatal Epigenome"],"prefix":"10.1210","volume":"107","author":[{"given":"Ives Yubin","family":"Lim","sequence":"first","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"},{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 119228, Singapore"},{"name":"Bioinformatics Institute (BII), A*STAR, 138671, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Lin","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"},{"name":"Centre for Quantitative Medicine, Duke-National University of Singapore (NUS) Medical School, 169857, Singapore"},{"name":"Singapore Clinical Research Institute, 138669, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai Ling","family":"Teh","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Wu","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglan","family":"He","sequence":"additional","affiliation":[{"name":"Duke-NUS Medical School, 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiao-Yng","family":"Chan","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"},{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L","family":"MacIsaac","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital Research Institute, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry K Y","family":"Chan","sequence":"additional","affiliation":[{"name":"KK Women\u2019s and Children\u2019s Hospital, 229899, Singapore"},{"name":"Saw Swee Hock School of Public Health, National University of Singapore (NUS), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kok Hian","family":"Tan","sequence":"additional","affiliation":[{"name":"KK Women\u2019s and Children\u2019s Hospital, 229899, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0587-2505","authenticated-orcid":false,"given":"Mary Foong Fong","family":"Chong","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"},{"name":"Saw Swee Hock School of Public Health, National University of Singapore (NUS), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Kobor","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital Research Institute, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith M","family":"Godfrey","sequence":"additional","affiliation":[{"name":"MRC Lifecourse Epidemiology Unit and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Meaney","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"},{"name":"Douglas Mental Health University Institute, McGill University, Montr\u00e9al, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung Seng","family":"Lee","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"},{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, NUS, 119228, Singapore"},{"name":"Division of Paediatric Endocrinology and Diabetes, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan G","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"},{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 119228, Singapore"},{"name":"Department of General Practice and Primary Health Care, University of Helsinki, Finland"},{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D","family":"Gluckman","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore"},{"name":"Centre for Human Evolution, Adaptation and Disease, Liggins Institute, University of Auckland, Auckland, 1142, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yap Seng","family":"Chong","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), 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