{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:37:37Z","timestamp":1786981057697,"version":"build-2736575974"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Epidemiol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Incidence of early-onset (&lt;\u200940 years) type 2 diabetes (T2D) is increasing. While multiple risk factors have been identified, particularly obesity and low socioeconomic status, early-life factors are hypothesised to play a role via fetal programming. We investigated sociodemographic and early-life factors in relation to early-onset T2D using a family-based design that accounts for shared genetic and environmental factors. We included 1,814,062 individuals born in Sweden 1983 to 2002 with follow-up data until 2020, and identified early-onset (age 19\u201339) T2D cases (n\u2009=\u20093505) through National Diabetes, Patient and Prescribed Drug Registers. Perinatal and sociodemographic factors were retrieved from registers. We used a cohort and sibling design, with multivariable-adjusted Cox proportional hazards regression. Sociodemographic factors associated with early-onset T2D included low parental education, single parenthood, younger parental age and non-Swedish origin. The latter association did not remain after mutual adjustment. Regarding perinatal factors, a higher incidence was noted in relation to lower birth weight (hazard ratio 2.38 [95% confidence interval: 1.98\u20132.87] and 1.43[1.33\u20131.54] for\u2009&lt;\u20092500\u00a0g and 2500-3500\u00a0g, respectively, vs 3500-4500\u00a0g), small-for-gestational-age (SGA) (2.24[1.96\u20132.56]), large-for-gestational-age (LGA) (1.19[1.01\u20131.39]), and maternal obesity (2.34[2.04\u20132.69]), diabetes (1.59[1.36\u20131.85]), smoking (1.59[1.48\u20131.71]), and infection (1.21[1.03\u20131.41]) during pregnancy. In the sibling analysis, only low birth weight and SGA remained associated with early-onset T2D. Early-onset T2D is associated with sociodemographic and multiple perinatal factors; only growth restriction likely reflects fetal programming, while other perinatal-related associations might involve confounders. This study highlights the need for early-life, targeted strategies to prevent T2D and reduce health inequities.<\/jats:p>","DOI":"10.1007\/s10654-025-01261-6","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T04:59:16Z","timestamp":1750741156000},"page":"845-857","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fetal programming of early-onset type 2 diabetes: a Swedish nationwide cohort and sibling analysis"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0581-7592","authenticated-orcid":false,"given":"Coralie","family":"Amadou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiinamaija","family":"Tuomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Feychting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Carlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"1261_CR1","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1152\/physrev.00002.2020","volume":"101","author":"DJ Hoffman","year":"2021","unstructured":"Hoffman DJ, Powell TL, Barrett ES, Hardy DB. Developmental origins of metabolic diseases. Physiol Rev. 2021;101:739\u201395.","journal-title":"Physiol Rev"},{"key":"1261_CR2","doi-asserted-by":"publisher","first-page":"405","DOI":"10.3389\/fped.2020.00405","volume":"8","author":"L Liao","year":"2020","unstructured":"Liao L, Deng Y, Zhao D. Association of low birth weight and premature birth with the risk of metabolic syndrome: a meta-analysis. Front Pediatr. 2020;8:405.","journal-title":"Front Pediatr"},{"key":"1261_CR3","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1016\/S0140-6736(86)91340-1","volume":"1","author":"DJ Barker","year":"1986","unstructured":"Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet Lond Engl. 1986;1:1077\u201381.","journal-title":"Lancet Lond Engl"},{"key":"1261_CR4","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-072385","volume":"379","author":"J Xie","year":"2022","unstructured":"Xie J, Wang M, Long Z, Ning H, Li J, Cao Y, et al. Global burden of type 2 diabetes in adolescents and young adults, 1990\u20132019: systematic analysis of the Global Burden of Disease Study 2019. BMJ. 2022;379: e072385.","journal-title":"BMJ"},{"key":"1261_CR5","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S2213-8587(23)00225-5","volume":"11","author":"S Misra","year":"2023","unstructured":"Misra S, Ke C, Srinivasan S, Goyal A, Nyriyenda MJ, Florez JC, et al. Current insights and emerging trends in early-onset type 2 diabetes. Lancet Diabetes Endocrinol. 2023;11:768\u201382.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"1261_CR6","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/s41581-022-00645-1","volume":"19","author":"P Bjornstad","year":"2023","unstructured":"Bjornstad P, Chao LC, Cree-Green M, Dart AB, King M, Looker HC, et al. Youth-onset type 2 diabetes mellitus: an urgent challenge. Nat Rev Nephrol. 2023;19:168\u201384.","journal-title":"Nat Rev Nephrol"},{"key":"1261_CR7","doi-asserted-by":"publisher","first-page":"490","DOI":"10.2337\/dci22-0046","volume":"46","author":"W Perng","year":"2023","unstructured":"Perng W, Conway R, Mayer-Davis E, Dabelea D. Youth-onset type 2 diabetes: the epidemiology of an awakening epidemic. Diabetes Care. 2023;46:490\u20139.","journal-title":"Diabetes Care"},{"key":"1261_CR8","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.2337\/dc07-2417","volume":"31","author":"D Dabelea","year":"2008","unstructured":"Dabelea D, Mayer-Davis EJ, Lamichhane AP, D\u2019Agostino RB, Liese AD, Vehik KS, et al. Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: the SEARCH Case-Control Study. Diabetes Care. 2008;31:1422\u20136.","journal-title":"Diabetes Care"},{"key":"1261_CR9","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/127452","volume":"2012","author":"K Millar","year":"2012","unstructured":"Millar K, Dean HJ. Developmental origins of type 2 diabetes in aboriginal youth in Canada: it is more than diet and exercise. J Nutr Metab. 2012;2012: 127452.","journal-title":"J Nutr Metab"},{"key":"1261_CR10","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1001\/archpedi.156.7.651","volume":"156","author":"TK Young","year":"2002","unstructured":"Young TK, Martens PJ, Taback SP, Sellers EAC, Dean HJ, Cheang M, et al. Type 2 diabetes mellitus in children: prenatal and early infancy risk factors among native Canadians. Arch Pediatr Adolesc Med. 2002;156:651\u20135.","journal-title":"Arch Pediatr Adolesc Med"},{"key":"1261_CR11","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1007\/s00125-007-0843-5","volume":"50","author":"N Lammi","year":"2007","unstructured":"Lammi N, Moltchanova E, Blomstedt P, Eriksson JG, Taskinen O, Sarti C, et al. The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults. Diabetologia. 2007;50:2433\u20138.","journal-title":"Diabetologia"},{"key":"1261_CR12","first-page":"1628","volume":"62","author":"MT Olaiya","year":"2019","unstructured":"Olaiya MT, Wedekind LE, Hanson RL, Sinha M, Kobes S, Nelson RG, et al. Birthweight and early-onset type 2 diabetes in American Indians: differential effects in adolescents and young adults and additive effects of genotype. BMI Maternal Diabetes Diabetologia. 2019;62:1628\u201337.","journal-title":"BMI Maternal Diabetes Diabetologia"},{"key":"1261_CR13","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1007\/s00125-019-05044-z","volume":"63","author":"C Crump","year":"2020","unstructured":"Crump C, Sundquist J, Sundquist K. Preterm birth and risk of type 1 and type 2 diabetes: a national cohort study. Diabetologia. 2020;63:508\u201318.","journal-title":"Diabetologia"},{"key":"1261_CR14","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1093\/aje\/kwaa183","volume":"190","author":"T Frisell","year":"2021","unstructured":"Frisell T. Invited commentary: sibling-comparison designs, are they worth the eFFORT? Am J Epidemiol. 2021;190:738\u201341.","journal-title":"Am J Epidemiol"},{"key":"1261_CR15","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s10519-015-9769-8","volume":"46","author":"BM D\u2019Onofrio","year":"2016","unstructured":"D\u2019Onofrio BM, Class QA, Rickert ME, Sujan AC, Larsson H, Kuja-Halkola R, et al. Translational epidemiologic approaches to understanding the consequences of early-life exposures. Behav Genet. 2016;46:315\u201328.","journal-title":"Behav Genet"},{"key":"1261_CR16","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/978-1-59745-423-0_10","volume":"675","author":"A Ekbom","year":"2011","unstructured":"Ekbom A. The Swedish multi-generation register. Methods Mol Biol Clifton NJ. 2011;675:215\u201320.","journal-title":"Methods Mol Biol Clifton NJ"},{"key":"1261_CR17","first-page":"1686","volume":"6","author":"NC Hamm","year":"2021","unstructured":"Hamm NC, Hamad AF, Wall-Wieler E, Roos LL, Plana-Ripoll O, Lix LM. Multigenerational health research using population-based linked databases: an international review. Int J Popul Data Sci. 2021;6:1686.","journal-title":"Int J Popul Data Sci."},{"key":"1261_CR18","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s10654-022-00947-5","volume":"38","author":"S Cnattingius","year":"2023","unstructured":"Cnattingius S, K\u00e4ll\u00e9n K, Sandstr\u00f6m A, Rydberg H, M\u00e5nsson H, Stephansson O, et al. The Swedish medical birth register during five decades: documentation of the content and quality of the register. Eur J Epidemiol. 2023;38:109\u201320.","journal-title":"Eur J Epidemiol"},{"key":"1261_CR19","unstructured":"Nationella Diabetesregistret [Internet]. [cited 2024 Jan 9]. Available from: https:\/\/www.ndr.nu\/#\/english"},{"key":"1261_CR20","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1186\/1471-2458-11-450","volume":"11","author":"JF Ludvigsson","year":"2011","unstructured":"Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim J-L, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.","journal-title":"BMC Public Health"},{"key":"1261_CR21","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/pds.1294","volume":"16","author":"B Wettermark","year":"2007","unstructured":"Wettermark B, Hammar N, MichaelFored C, Leimanis A, Otterblad Olausson P, Bergman U, et al. The new Swedish Prescribed Drug Register\u2014Opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf. 2007;16:726\u201335.","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"1261_CR22","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s10654-019-00511-8","volume":"34","author":"JF Ludvigsson","year":"2019","unstructured":"Ludvigsson JF, Svedberg P, Ol\u00e9n O, Bruze G, Neovius M. The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research. Eur J Epidemiol. 2019;34:423\u201337.","journal-title":"Eur J Epidemiol"},{"key":"1261_CR23","first-page":"A25","volume":"46","author":"I Zachrisson","year":"2003","unstructured":"Zachrisson I, Tibell C, Bang P, Ortqvist E. Prevalence of type 2 diabetes among known cases of diabetes aged 0\u201318 years in Sweden (Abstract). Diabetologia. 2003;46:A25.","journal-title":"Diabetologia"},{"key":"1261_CR24","doi-asserted-by":"publisher","unstructured":"Svensson A-M, Eliasson B, Linder E, Almskog I, Eeg-Olofsson K, Miftaraj M, et al. The Swedish National Diabetes Register (NDR) - Nationwide results 1996\u20132020 [Internet]. The Swedish National Diabetes Register; 2021 p. 16473344 byte. Available from: https:\/\/registercentrum.blob.core.windows.net\/refdocs\/https:\/\/doi.org\/10.18158\/SJeNL4Vwiu.pdf","DOI":"10.18158\/SJeNL4Vwiu.pdf"},{"key":"1261_CR25","doi-asserted-by":"crossref","unstructured":"ACOG Committee Opinion No 579: Definition of term pregnancy. Obstet Gynecol. 2013;122:1139\u201340.","DOI":"10.1097\/01.AOG.0000437385.88715.4a"},{"issue":"85","key":"1261_CR26","first-page":"843","volume":"1996","author":"K Mars\u00e1l","year":"1992","unstructured":"Mars\u00e1l K, Persson PH, Larsen T, Lilja H, Selbing A, Sultan B. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr Oslo Nor. 1992;1996(85):843\u20138.","journal-title":"Acta Paediatr Oslo Nor"},{"key":"1261_CR27","doi-asserted-by":"publisher","first-page":"347","DOI":"10.3945\/ajcn.2010.29247","volume":"92","author":"EDL Rolfe","year":"2010","unstructured":"Rolfe EDL, Loos RJF, Druet C, Stolk RP, Ekelund U, Griffin SJ, et al. Association between birth weight and visceral fat in adults. Am J Clin Nutr. 2010;92:347\u201352.","journal-title":"Am J Clin Nutr"},{"key":"1261_CR28","doi-asserted-by":"publisher","first-page":"R63","DOI":"10.1530\/JOE-17-0076","volume":"235","author":"BH Boehmer","year":"2017","unstructured":"Boehmer BH, Limesand SW, Rozance PJ. The impact of IUGR on pancreatic islet development and \u03b2-cell function. J Endocrinol. 2017;235:R63-76.","journal-title":"J Endocrinol"},{"key":"1261_CR29","doi-asserted-by":"publisher","first-page":"100957","DOI":"10.1016\/j.arr.2019.100957","volume":"55","author":"A Vaiserman","year":"2019","unstructured":"Vaiserman A, Lushchak O. Developmental origins of type 2 diabetes: Focus on epigenetics. Ageing Res Rev. 2019;55:100957.","journal-title":"Ageing Res Rev"},{"key":"1261_CR30","doi-asserted-by":"publisher","first-page":"459","DOI":"10.3390\/jcm10030459","volume":"10","author":"A Sarkar","year":"2021","unstructured":"Sarkar A, Yoo JY, Valeria Ozorio Dutra S, Morgan KH, Groer M. The association between early-life gut microbiota and long-term health and diseases. J Clin Med. 2021;10:459.","journal-title":"J Clin Med"},{"key":"1261_CR31","unstructured":"American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes\u20142024. Diabetes Care. 2023;47:S20\u201342."},{"key":"1261_CR32","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.2337\/diabetes.49.12.2208","volume":"49","author":"D Dabelea","year":"2000","unstructured":"Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Gabir MM, et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. 2000;49:2208\u201311.","journal-title":"Diabetes"},{"key":"1261_CR33","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1462-8902.2004.00330.x","volume":"6","author":"L Molyneaux","year":"2004","unstructured":"Molyneaux L, Constantino M, Yue D. Strong family history predicts a younger age of onset for subjects diagnosed with type 2 diabetes. Diabetes Obes Metab. 2004;6:187\u201394.","journal-title":"Diabetes Obes Metab"}],"container-title":["European Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-025-01261-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10654-025-01261-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-025-01261-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T22:10:40Z","timestamp":1757196640000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10654-025-01261-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["1261"],"URL":"https:\/\/doi.org\/10.1007\/s10654-025-01261-6","relation":{},"ISSN":["0393-2990","1573-7284"],"issn-type":[{"value":"0393-2990","type":"print"},{"value":"1573-7284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]},"assertion":[{"value":"12 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This nationwide cohort study was approved by the Swedish Ethics Review Board (registration number: Dnr 2021\u201302881).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}