{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:52:36Z","timestamp":1787025156750,"version":"build-2736575974"},"reference-count":39,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T00:00:00Z","timestamp":1555891200000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["79896"],"award-info":[{"award-number":["79896"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["158616"],"award-info":[{"award-number":["158616"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81571451"],"award-info":[{"award-number":["81571451"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Fetal excessive exposure to glucocorticoids may program cardiometabolic risk. Placental 11 \u03b2-hydroxysteroid dehydrogenase 2 (11\u03b2-HSD2) serves as a barrier to prevent fetal overexposure to maternal glucocorticoids. It has not been explored whether placental 11\u03b2-HSD2 levels are associated with cardiometabolic health in postnatal life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>In a prospective birth cohort study of 246 mother-infant pairs, we measured placental 11\u03b2-HSD2 expression and maternal (32\u201335 weeks of gestation) and cord plasma cortisol concentrations. The primary outcomes were HOMA of insulin resistance (IR) and blood pressure (BP) in infants at age 1 year. Other outcomes included fasting insulin, HOMA \u03b2-cell function, carotid intima-media thickness, weight z score, and skinfold thickness (triceps and subscapular) at age 1 year.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Placental 11\u03b2-HSD2 expression was negatively correlated with HOMA-IR (r = \u22120.17, P = 0.021) and fasting insulin (r = \u22120.18, P = 0.017) and marginally negatively correlated with systolic BP (r = \u22120.16, P = 0.057) but was not correlated with HOMA of \u03b2-cell function, diastolic BP, carotid intima-media thickness, and skinfold thickness (all P &amp;gt; 0.1) in infants at age 1 year. Cord plasma cortisol was negatively correlated to skinfold thickness (r = \u22120.20, P = 0007) but was not correlated with other outcomes at age 1 year. Maternal plasma cortisol was positively correlated with maximal carotid intima-media thickness (r = 0.20, P = 0.03) but was not correlated with other outcomes. Adjusting for maternal and infant characteristics, the associations were similar.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The study is the first to show that higher placental 11\u03b2-HSD2 expression is associated with lower IR in infancy. Independent cohort studies are required to confirm this novel finding.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc18-2041","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T21:25:23Z","timestamp":1551734723000},"page":"964-971","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":15,"title":["Placental 11\u03b2-HSD2 and Cardiometabolic Health Indicators in Infancy"],"prefix":"10.2337","volume":"42","author":[{"given":"Lu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Prosserman Center for Population Health Research, Mount Sinai Hospital, and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada"},{"name":"Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Quebec, Canada"},{"name":"Ministry of Education-Shanghai Key Laboratory of Children\u2019s Environmental Health, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Guilmette","sequence":"additional","affiliation":[{"name":"Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Quebec, Canada"},{"name":"Department of Pathology, Charles-Lemoyne Hospital, Longueuil, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-1312","authenticated-orcid":false,"given":"Zhong-Cheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Prosserman Center for Population Health Research, Mount Sinai Hospital, and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada"},{"name":"Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anik","family":"Cloutier","sequence":"additional","affiliation":[{"name":"Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Prosserman Center for Population Health Research, Mount Sinai Hospital, and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada"},{"name":"Ministry of Education-Shanghai Key Laboratory of Children\u2019s Environmental Health, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Nan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Prosserman Center for Population Health Research, Mount Sinai Hospital, and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada"},{"name":"Ministry of Education-Shanghai Key Laboratory of Children\u2019s Environmental Health, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Quebec, Canada"},{"name":"Obstetrics and Gynecology, University of Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9e","family":"Dubois","sequence":"additional","affiliation":[{"name":"Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Monique","family":"Nuyt","sequence":"additional","affiliation":[{"name":"Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2019,3,4]]},"reference":[{"key":"2022031303273922500_B1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/ije\/dyt133","article-title":"Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. 1992","volume":"42","author":"Hales","year":"2013","journal-title":"Int J Epidemiol"},{"key":"2022031303273922500_B2","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1126\/science.1095292","article-title":"Living with the past: evolution, development, and patterns of disease","volume":"305","author":"Gluckman","year":"2004","journal-title":"Science"},{"key":"2022031303273922500_B3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11154-008-9087-z","article-title":"Maternal nutrition, intrauterine programming and consequential risks in the offspring","volume":"9","author":"Yajnik","year":"2008","journal-title":"Rev Endocr Metab Disord"},{"key":"2022031303273922500_B4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1017\/S2040174412000311","article-title":"Nick Hales Award Lecture 2011: glucocorticoids and early life programming of cardiometabolic disease","volume":"3","author":"Reynolds","year":"2012","journal-title":"J Dev Orig Health Dis"},{"key":"2022031303273922500_B5","doi-asserted-by":"crossref","first-page":"U49","DOI":"10.1530\/eje.0.151u049","article-title":"Prenatal glucocorticoids and long-term programming","volume":"151","author":"Seckl","year":"2004","journal-title":"Eur J Endocrinol"},{"key":"2022031303273922500_B6","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1210\/jc.2010-2395","article-title":"A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum","volume":"96","author":"Jung","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031303273922500_B7","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1079\/PNS19980017","article-title":"Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance","volume":"57","author":"Fowden","year":"1998","journal-title":"Proc Nutr Soc"},{"key":"2022031303273922500_B8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1071\/RD9940141","article-title":"The role of cortisol in preparing the fetus for birth","volume":"6","author":"Liggins","year":"1994","journal-title":"Reprod Fertil Dev"},{"key":"2022031303273922500_B9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1159\/000235879","article-title":"Differential expression and activity of 11beta-hydroxysteroid dehydrogenase in human placenta and fetal membranes from pregnancies with intrauterine growth restriction","volume":"25","author":"W\u00e4chter","year":"2009","journal-title":"Fetal Diagn Ther"},{"key":"2022031303273922500_B10","first-page":"885","article-title":"Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis","volume":"80","author":"Stewart","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031303273922500_B11","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1136\/bmj.311.6998.171","article-title":"Fetal origins of coronary heart disease","volume":"311","author":"Barker","year":"1995","journal-title":"BMJ"},{"key":"2022031303273922500_B12","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1203\/00006450-197305000-00004","article-title":"The metabolic clearance rate, blood production, interconversion and transplacental passage of cortisol and cortisone in pregnancy near term","volume":"7","author":"Beitins","year":"1973","journal-title":"Pediatr Res"},{"key":"2022031303273922500_B13","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.neuroscience.2005.09.037","article-title":"11beta-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoids","volume":"137","author":"Holmes","year":"2006","journal-title":"Neuroscience"},{"key":"2022031303273922500_B14","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1161\/01.HYP.27.6.1200","article-title":"Inhibition of 11-beta-hydroxysteroid dehydrogenase in pregnant rats and the programming of blood pressure in the offspring","volume":"27","author":"Lindsay","year":"1996","journal-title":"Hypertension"},{"key":"2022031303273922500_B15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1677\/joe.0.1720071","article-title":"The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function","volume":"172","author":"Sloboda","year":"2002","journal-title":"J Endocrinol"},{"key":"2022031303273922500_B16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1113\/jphysiol.1997.sp021922","article-title":"A comparative study of cardiovascular, endocrine and behavioural effects of betamethasone and dexamethasone administration to fetal sheep","volume":"499","author":"Derks","year":"1997","journal-title":"J Physiol"},{"key":"2022031303273922500_B17","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.2337\/dc10-0819","article-title":"Maternal glucose tolerance in pregnancy affects fetal insulin sensitivity","volume":"33","author":"Luo","year":"2010","journal-title":"Diabetes Care"},{"key":"2022031303273922500_B18","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1111\/dme.13671","article-title":"Cord blood insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin, and their associations with insulin sensitivity, \u03b2-cell function and adiposity in infancy","volume":"35","author":"Zhang","year":"2018","journal-title":"Diabet Med"},{"key":"2022031303273922500_B19","volume-title":"WHO Child Growth Standards: Length\/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height, and Body Mass Index-for-Age: Methods and Development","author":"WHO Multicentre Growth Reference Study Group","year":"2006"},{"key":"2022031303273922500_B20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000081913","article-title":"Design, baseline characteristics and carotid intima-media thickness reproducibility in the PARC study","volume":"19","author":"Touboul","year":"2005","journal-title":"Cerebrovasc Dis"},{"key":"2022031303273922500_B21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1741-7015-6-25","article-title":"Association between umbilical cord glucocorticoids and blood pressure at age 3 years","volume":"6","author":"Huh","year":"2008","journal-title":"BMC Med"},{"key":"2022031303273922500_B22","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"2022031303273922500_B23","doi-asserted-by":"crossref","first-page":"E35","DOI":"10.1542\/peds.108.2.e35","article-title":"A new and improved population-based Canadian reference for birth weight for gestational age","volume":"108","author":"Kramer","year":"2001","journal-title":"Pediatrics"},{"key":"2022031303273922500_B24","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev-publhealth-032315-021402","article-title":"Mediation analysis: a practitioner\u2019s guide","volume":"37","author":"VanderWeele","year":"2016","journal-title":"Annu Rev Public Health"},{"key":"2022031303273922500_B25","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/j.1471-0528.2006.00865.x","article-title":"Mode of delivery is associated with maternal and fetal endocrine stress response","volume":"113","author":"Vogl","year":"2006","journal-title":"BJOG"},{"key":"2022031303273922500_B26","first-page":"928","article-title":"Relationship between 11\u03b2-HSD2 mRNA and insulin sensitivity in term small-for-gestational age neonates after birth","volume":"8","author":"Zhu","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"2022031303273922500_B27","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1016\/S0026-0495(99)90249-4","article-title":"Influence of placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD) inhibition on glucose metabolism and 11beta-HSD regulation in adult offspring of rats","volume":"48","author":"Saegusa","year":"1999","journal-title":"Metabolism"},{"key":"2022031303273922500_B28","doi-asserted-by":"crossref","first-page":"E592","DOI":"10.1152\/ajpendo.2001.281.3.E592","article-title":"Glucocorticoids impair fetal beta-cell development in rats","volume":"281","author":"Blondeau","year":"2001","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031303273922500_B29","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1196\/annals.1290.016","article-title":"Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum","volume":"997","author":"Mastorakos","year":"2003","journal-title":"Ann N Y Acad Sci"},{"key":"2022031303273922500_B30","first-page":"452","article-title":"Physiological concentrations of serum cortisol are related to vascular risk markers in prepubertal children","volume":"68","author":"Soriano-Rodr\u00edguez","year":"2010","journal-title":"Pediatr Res"},{"key":"2022031303273922500_B31","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1097\/HJH.0000000000001065","article-title":"Feasibility and reliability of carotid intima-media thickness measurements in nonsedated infants","volume":"34","author":"Mivelaz","year":"2016","journal-title":"J Hypertens"},{"key":"2022031303273922500_B32","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/AC.70.3.3080640","article-title":"Intima-media complex thickness: preliminary workup of comparative evaluation of abdominal aorta and carotid artery of small-for-gestation-age term newborns and normal size term newborns","volume":"70","author":"Sodhi","year":"2015","journal-title":"Acta Cardiol"},{"key":"2022031303273922500_B33","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/uog.13245","article-title":"Aortic and carotid intima-media thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity","volume":"43","author":"Stergiotou","year":"2014","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2022031303273922500_B34","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/pr.2015.182","article-title":"Influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction","volume":"79","author":"Rodriguez-Lopez","year":"2016","journal-title":"Pediatr Res"},{"key":"2022031303273922500_B35","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.steroids.2012.03.007","article-title":"Differential expression of placental 11\u03b2-hydroxysteroid dehydrogenases in pregnant women with diet-treated gestational diabetes mellitus","volume":"77","author":"Ma","year":"2012","journal-title":"Steroids"},{"key":"2022031303273922500_B36","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/jp.2012.165","article-title":"ACTH and cortisol cord plasma concentrations in preterm and term infants","volume":"33","author":"Bagnoli","year":"2013","journal-title":"J Perinatol"},{"key":"2022031303273922500_B37","doi-asserted-by":"crossref","first-page":"S257","DOI":"10.1016\/S0002-9378(99)70712-X","article-title":"Maternal plasma corticotropin-releasing hormone associated with stress at 20 weeks\u2019 gestation in pregnancies ending in preterm delivery","volume":"180","author":"Hobel","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"2022031303273922500_B38","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ejogrb.2012.08.009","article-title":"Abnormal fetomaternal glucocorticoid metabolism in the background of premature delivery: placental expression patterns of the 11\u03b2-hydroxysteroid dehydrogenase 2 gene","volume":"165","author":"Demendi","year":"2012","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2022031303273922500_B39","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1093\/humrep\/13.4.799","article-title":"11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction","volume":"13","author":"Shams","year":"1998","journal-title":"Hum Reprod"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/care.diabetesjournals.org\/syndication\/doi\/10.2337\/dc18-2041","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/42\/5\/964\/553200\/dc182041.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/42\/5\/964\/553200\/dc182041.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T03:59:02Z","timestamp":1647143942000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/42\/5\/964\/40532\/Placental-11-HSD2-and-Cardiometabolic-Health"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,4]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,3,4]]},"published-print":{"date-parts":[[2019,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc18-2041","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,4]]}}}