{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T02:50:44Z","timestamp":1746499844946,"version":"3.37.3"},"reference-count":40,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K50127X\/1"],"award-info":[{"award-number":["MR\/K50127X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013112","name":"Raymond & Beverly Sackler Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013112","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004966","name":"European Union Framework 5","doi-asserted-by":"publisher","award":["QLK4-1999-01422"],"award-info":[{"award-number":["QLK4-1999-01422"]}],"id":[{"id":"10.13039\/501100004966","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mothercare Charitable Foundation","award":["RG54608"],"award-info":[{"award-number":["RG54608"]}]},{"DOI":"10.13039\/501100000871","name":"Newlife Foundation for Disabled Children","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013743","name":"World Cancer Research Fund International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013743","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Vitamin D has been variably implicated in risk of developing type 1 diabetes based on cohorts of at-risk individuals. Emergent type 1 diabetes in childhood is putatively preceded by altered growth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We explored whether polymorphisms in vitamin D metabolism genes modify risk of type 1 diabetes via effects on growth in a prospective, population-based cohort of infants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The Cambridge Baby Growth Study enrolled newborns from Cambridgeshire, UK, for follow-up in infancy. In 612 infants, we genotyped single nucleotide polymorphisms in vitamin D metabolism genes that relate with type 1 diabetes: rs10741657 and rs12794714 in CYP2R1, rs12785878 in DHCR7, and rs10877012 in CYP27B1. Multivariate linear regression analyses tested associations between genotypes and anthropometric indices (weight, length, and skinfold thickness) or growth-related hormones (C-peptide, IGF-1, and leptin) in infancy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Birth weight showed borderline associations with the diabetes risk\u2013increasing alleles in CYP2R1, rs10741657 (\u03b2 = \u2212.11, P = .02) and rs12794714 (\u03b2 = \u2212.09, P = .04). The risk-increasing allele rs12794714 was also associated with higher IGF-1 levels at age 24 months (\u03b2 = .30, P = .01). At age 3 months, the risk-increasing allele rs12785878 in DHCR7, known to negatively associate with 25-hydroxyvitamin D levels, showed a positive association with leptin levels (\u03b2 = .23, P = .009), which was pronounced in girls (P = .004) vs boys (P = .7).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The vitamin D metabolism genes DHCR7 and CYP2R1 might influence infancy leptin and IGF-1 levels respectively. These findings open the possibility for a developmental role of vitamin D that is mediated by growth-related hormones with implications for the onset of type 1 diabetes autoimmunity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad263","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T08:42:53Z","timestamp":1683880973000},"page":"e1394-e1402","source":"Crossref","is-referenced-by-count":1,"title":["Leptin and IGF-1 in Infancy Are Associated With Variants in <i>DHCR7<\/i> and <i>CYP2R1<\/i> That Relate With Type 1 Diabetes and 25OHD"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-719X","authenticated-orcid":false,"given":"Antigoni","family":"Eleftheriou","sequence":"first","affiliation":[{"name":"Department of Paediatrics, University of Cambridge , Cambridge CB2 0QQ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-7530","authenticated-orcid":false,"given":"Ken K","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Cambridge , Cambridge CB2 0QQ , UK"},{"name":"MRC Epidemiology Unit, University of Cambridge , Cambridge CB2 0QQ , UK"},{"name":"Institute of Metabolic Science, University of Cambridge , Cambridge CB2 0QQ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-1575","authenticated-orcid":false,"given":"Ieuan A","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Cambridge , Cambridge CB2 0QQ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6642-9825","authenticated-orcid":false,"given":"Clive J","family":"Petry","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Cambridge , Cambridge CB2 0QQ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"issue":"4","key":"2023101816060564400_dgad263-B1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.immuni.2010.04.001","article-title":"Etiology of type 1 diabetes","volume":"32","author":"Todd","year":"2010","journal-title":"Immunity"},{"issue":"2","key":"2023101816060564400_dgad263-B2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ecl.2010.02.010","article-title":"Vitamin D and the immune system: new perspectives on an old theme","volume":"39","author":"Hewison","year":"2010","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"10","key":"2023101816060564400_dgad263-B3","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.2337\/db07-0652","article-title":"Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes","volume":"56","author":"Bailey","year":"2007","journal-title":"Diabetes"},{"issue":"5","key":"2023101816060564400_dgad263-B4","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.2337\/db10-1656","article-title":"Inherited variation in vitamin D genes is associated with predisposition to autoimmune disease type 1 diabetes","volume":"60","author":"Cooper","year":"2011","journal-title":"Diabetes"},{"issue":"9736","key":"2023101816060564400_dgad263-B5","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0140-6736(10)60588-0","article-title":"Common genetic determinants of vitamin D insufficiency: a genome-wide association study","volume":"376","author":"Wang","year":"2010","journal-title":"Lancet"},{"issue":"7","key":"2023101816060564400_dgad263-B6","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/j.1464-5491.2009.02743.x","article-title":"Seasonal variation of diagnosis of type 1 diabetes mellitus in children worldwide","volume":"26","author":"Moltchanova","year":"2009","journal-title":"Diabet Med"},{"issue":"6","key":"2023101816060564400_dgad263-B7","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1093\/ije\/23.6.1234","article-title":"Childhood onset diabetes\u2013time trends and climatological factors","volume":"23","author":"Dahlquist","year":"1994","journal-title":"Int J Epidemiol"},{"issue":"6","key":"2023101816060564400_dgad263-B8","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1093\/aje\/kwx361","article-title":"Lack of association between maternal or neonatal vitamin D status and risk of childhood type 1 diabetes: a Scandinavian case-cohort study","volume":"187","author":"Thorsen","year":"2018","journal-title":"Am J Epidemiol"},{"issue":"2","key":"2023101816060564400_dgad263-B9","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1210\/jc.2015-3504","article-title":"Serum 25-hydroxyvitamin D concentrations in children progressing to autoimmunity and clinical type 1 diabetes","volume":"101","author":"M\u00e4kinen","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"2023101816060564400_dgad263-B10","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1007\/s00125-011-2278-2","article-title":"No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY)","volume":"54","author":"Simpson","year":"2011","journal-title":"Diabetologia"},{"issue":"1","key":"2023101816060564400_dgad263-B11","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2337\/db17-0802","article-title":"Plasma 25-hydroxyvitamin D concentration and risk of islet autoimmunity","volume":"67","author":"Norris","year":"2018","journal-title":"Diabetes"},{"issue":"8","key":"2023101816060564400_dgad263-B12","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1093\/aje\/kwj278","article-title":"Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a HuGE review of genetic association studies","volume":"164","author":"Guo","year":"2006","journal-title":"Am J Epidemiol"},{"issue":"4","key":"2023101816060564400_dgad263-B13","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1007\/s00125-019-05077-4","article-title":"Serum 25-hydroxyvitamin D concentration in childhood and risk of islet autoimmunity and type 1 diabetes: the TRIGR nested case\u2013control ancillary study","volume":"63","author":"Miettinen","year":"2020","journal-title":"Diabetologia"},{"issue":"5","key":"2023101816060564400_dgad263-B14","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s11892-008-0068-0","article-title":"Diabetes and the vitamin D connection","volume":"8","author":"Holick","year":"2008","journal-title":"Curr Diab Rep"},{"issue":"3","key":"2023101816060564400_dgad263-B15","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1007\/s00125-017-4493-y","article-title":"Associations between birthweight, gestational age at birth and subsequent type 1 diabetes in children under 12: a retrospective cohort study in England, 1998-2012","volume":"61","author":"Goldacre","year":"2018","journal-title":"Diabetologia"},{"issue":"3","key":"2023101816060564400_dgad263-B16","doi-asserted-by":"crossref","first-page":"556","DOI":"10.2337\/dc19-1670","article-title":"Distinct growth phases in early life associated with the risk of type 1 diabetes: the TEDDY study","volume":"43","author":"Liu","year":"2020","journal-title":"Diabetes Care"},{"issue":"12","key":"2023101816060564400_dgad263-B17","doi-asserted-by":"crossref","DOI":"10.1001\/jamapediatrics.2015.3759","article-title":"Infant growth and risk of childhood-onset type 1 diabetes in children from 2 Scandinavian birth cohorts","volume":"169","author":"Magnus","year":"2015","journal-title":"JAMA Pediatr"},{"issue":"8","key":"2023101816060564400_dgad263-B18","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.2337\/dc20-2820","article-title":"The high-risk type 1 diabetes HLA-DR and HLA-DQ polymorphisms are differentially associated with growth and IGF-I levels in infancy: the Cambridge baby growth study","volume":"44","author":"Eleftheriou","year":"2021","journal-title":"Diabetes Care"},{"issue":"1","key":"2023101816060564400_dgad263-B19","doi-asserted-by":"crossref","first-page":"T115","DOI":"10.1530\/JME-17-0298","article-title":"40 YEARS OF IGF1: insulin-like growth factors: actions on the skeleton","volume":"61","author":"Yakar","year":"2018","journal-title":"J Mol Endocrinol"},{"issue":"1","key":"2023101816060564400_dgad263-B20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/ije\/dyv318","article-title":"Cohort profile: the Cambridge Baby Growth Study (CBGS)","volume":"45","author":"Prentice","year":"2016","journal-title":"Int J Epidemiol"},{"issue":"10","key":"2023101816060564400_dgad263-B21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0046752","article-title":"Filter paper blood spot enzyme linked immunoassay for insulin and application in the evaluation of determinants of child insulin resistance","volume":"7","author":"Martin","year":"2012","journal-title":"PLoS One"},{"issue":"5","key":"2023101816060564400_dgad263-B22","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1210\/jcem-70-5-1292","article-title":"A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency","volume":"70","author":"Blum","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"issue":"2-3","key":"2023101816060564400_dgad263-B23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1096-6374(03)00004-2","article-title":"Measuring IGF-I, IGFBP-2 and IGFBP-3 from dried blood spots on filter paper is not only practical but also reliable","volume":"13","author":"Sch\u00fctt","year":"2003","journal-title":"Growth Horm IGF Res"},{"issue":"21","key":"2023101816060564400_dgad263-B24","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.1093\/bioinformatics\/btv402","article-title":"LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants","volume":"31","author":"Machiela","year":"2015","journal-title":"Bioinformatics"},{"author":"Pan","key":"2023101816060564400_dgad263-B25"},{"issue":"1","key":"2023101816060564400_dgad263-B26","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3945\/ajcn.2008.27408","article-title":"Insulin-like growth factor I concentrations in infancy predict differential gains in body length and adiposity: the Cambridge baby growth study","volume":"90","author":"Ong","year":"2009","journal-title":"Am J Clin Nutr"},{"issue":"11","key":"2023101816060564400_dgad263-B27","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.2337\/db11-0650","article-title":"Vitamin D, insulin secretion, sensitivity, and lipids: results from a case-control study and a randomized controlled trial using hyperglycemic clamp technique","volume":"60","author":"Grimnes","year":"2011","journal-title":"Diabetes"},{"key":"2023101816060564400_dgad263-B28","doi-asserted-by":"crossref","DOI":"10.1038\/srep16142","article-title":"The effect of vitamin D supplementation on insulin and glucose metabolism in overweight and obese individuals: systematic review with meta-analysis","volume":"5","author":"Jamka","year":"2015","journal-title":"Sci Rep"},{"issue":"12","key":"2023101816060564400_dgad263-B29","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1017\/S0007114518000879","article-title":"Concentration of 25-hydroxyvitamin D from neonatal dried blood spots and the relation to gestational age, birth weight and Ponderal Index: the D-tect study","volume":"119","author":"Keller","year":"2018","journal-title":"Br J Nutr"},{"issue":"16","key":"2023101816060564400_dgad263-B30","doi-asserted-by":"crossref","first-page":"8363","DOI":"10.1074\/jbc.M115.699546","article-title":"Cholesterol-mediated degradation of 7-dehydrocholesterol reductase switches the balance from cholesterol to vitamin D synthesis","volume":"291","author":"Prabhu","year":"2016","journal-title":"J Biol Chem"},{"issue":"10","key":"2023101816060564400_dgad263-B31","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/ejcn.2016.245","article-title":"Vitamin D and serum leptin: a systematic review and meta-analysis of observational studies and randomized controlled trials","volume":"71","author":"Hajimohammadi","year":"2017","journal-title":"Eur J Clin Nutr"},{"issue":"1-2","key":"2023101816060564400_dgad263-B32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1023\/A:1012947113197","article-title":"Leptin and the hypothalamic-pituitary regulation of the gonadotropin-gonadal axis","volume":"4","author":"Chan","year":"2001","journal-title":"Pituitary"},{"issue":"2","key":"2023101816060564400_dgad263-B33","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1530\/eje.0.1460261","article-title":"Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells","volume":"146","author":"Tezuka","year":"2002","journal-title":"Eur J Endocrinol"},{"key":"2023101816060564400_dgad263-B34","doi-asserted-by":"crossref","first-page":"410","DOI":"10.3389\/fendo.2018.00410","article-title":"Up-to-date review about minipuberty and overview on hypothalamic-pituitary-gonadal axis activation in fetal and neonatal life","volume":"9","author":"Lanciotti","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2023101816060564400_dgad263-B35","doi-asserted-by":"crossref","first-page":"13169","DOI":"10.1038\/s41598-018-31583-3","article-title":"Minipuberty and sexual dimorphism in the infant human thymus","volume":"8","author":"Moreira-Filho","year":"2018","journal-title":"Sci Rep"},{"issue":"D1","key":"2023101816060564400_dgad263-B36","doi-asserted-by":"crossref","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS catalog of published genome-wide association studies, targeted arrays and summary statistics 2019","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"2023101816060564400_dgad263-B37","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1080\/09168451.2014.942250","article-title":"Enzymes for ecdysteroid biosynthesis: their biological functions in insects and beyond","volume":"78","author":"Niwa","year":"2014","journal-title":"Biosci Biotechnol Biochem"},{"issue":"5","key":"2023101816060564400_dgad263-B38","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1111\/j.1742-4658.2008.06859.x","article-title":"An ecdysteroid-inducible insulin-like growth factor-like peptide regulates adult development of the silkmoth Bombyx mori","volume":"276","author":"Okamoto","year":"2009","journal-title":"FEBS J"},{"issue":"8","key":"2023101816060564400_dgad263-B39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001866","article-title":"Vitamin D and risk of multiple sclerosis: a Mendelian randomization study","volume":"12","author":"Mokry","year":"2015","journal-title":"PLoS Med"},{"issue":"1","key":"2023101816060564400_dgad263-B40","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.metabol.2014.10.014","article-title":"Leptin in autoimmune diseases","volume":"64","author":"Procaccini","year":"2015","journal-title":"Metabolism"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgad263\/50416689\/dgad263.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/11\/e1394\/52218023\/dgad263.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/11\/e1394\/52218023\/dgad263.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T16:11:08Z","timestamp":1697645468000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/108\/11\/e1394\/7160562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,12]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,5,12]]},"published-print":{"date-parts":[[2023,10,18]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgad263","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"type":"print","value":"0021-972X"},{"type":"electronic","value":"1945-7197"}],"subject":[],"published-other":{"date-parts":[[2023,11]]},"published":{"date-parts":[[2023,5,12]]}}}