{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T12:00:44Z","timestamp":1769947244781,"version":"3.49.0"},"reference-count":44,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The prevalence of both asthma and early-onset diabetes is on the rise; however, the association between them remains unclear. We examined a possible association of asthma at adolescence with type 2 diabetes in young adulthood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This is a nationwide, population-based study of 1 718 541 Israeli adolescents (57% males; mean age 17.3 years; range 16-19 years), examined before compulsory military service between 1992 and 2016, with data linked to the Israeli National Diabetes Registry. Asthma diagnosis and severity were determined by a board-certified pulmonologist and based on spirometry tests.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Type 2 diabetes developed in 58\/9090 (0.64%), 507\/97 059 (0.52%), 114\/23 332 (0.49%), and 7095\/1 589 060 (0.44%) persons with moderate-to-severe, mild, inactive, and no history of asthma, respectively, during a mean follow-up &amp;gt;13 years. The respective odds ratios (ORs) were 1.33 (95% CI, 1.02-1.74), 1.17 (1.06-1.28), and 1.09 (0.9-1.31), considering those without asthma history as the reference, in a model adjusted for birth year, sex, body mass index, and other sociodemographic variables. The association persisted when the analysis accounted for coexisting morbidities, and when persons without asthma, individually matched by age, sex, birth year, and body mass index were the reference. Both mild and moderate-to-severe asthma were associated with type 2 diabetes before age 35 years: ORs 1.18 (1.05-1.34) and 1.44 (1.05-2.00), respectively. The strength of the association was accentuated over time. The effect was unchanged when adjusted for oral and inhaled glucocorticoid use.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Adolescents with active asthma have higher risk to develop type 2 diabetes. This seems related to disease severity, independent of adolescent obesity status, apparent before age 35 years, and more pronounced in recent years.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab542","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T10:41:33Z","timestamp":1626950493000},"source":"Crossref","is-referenced-by-count":4,"title":["Asthma in Youth and Early-onset Type 2 Diabetes: A Nationwide Study of 1.72 Million Israeli Adolescents"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-6974","authenticated-orcid":false,"given":"Michael","family":"Shapiro","sequence":"first","affiliation":[{"name":"Department of Internal Medicine T, Tel Aviv Sourasky Medical Center, Tel Aviv 6492601, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Arbel","sequence":"additional","affiliation":[{"name":"Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel"},{"name":"Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inbar","family":"Zucker","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"The Israel Center for Disease Control, Ministry of Health, Ramat Gan 5262160, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gingy Ronen","family":"Balmor","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Shamir (Assaf-Harofeh) Medical Center, Zerifin 70300, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miri","family":"Lutski","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"The Israel Center for Disease Control, Ministry of Health, Ramat Gan 5262160, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estela","family":"Derazne","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zivan","family":"Beer","sequence":"additional","affiliation":[{"name":"Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel"},{"name":"Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orit","family":"Pinhas-Hamiel","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Department of Pediatric Endocrinology, Safra Children Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ofri","family":"Mosenzon","sequence":"additional","affiliation":[{"name":"The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorit","family":"Tzur","sequence":"additional","affiliation":[{"name":"Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel"},{"name":"Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnon","family":"Afek","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2210-5906","authenticated-orcid":false,"given":"Amir","family":"Tirosh","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tali","family":"Cukierman-Yaffe","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hertzel C","family":"Gerstein","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, Ontario L8S 4M1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vered","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Maccabitech Research Institute, Maccabi Healthcare Services, Tel Aviv 6801296, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Chodick","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Maccabitech Research Institute, Maccabi Healthcare Services, Tel Aviv 6801296, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itamar","family":"Raz","sequence":"additional","affiliation":[{"name":"The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2829-3645","authenticated-orcid":false,"given":"Gilad","family":"Twig","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel"},{"name":"Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel"},{"name":"Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"2021091807313134100_CIT0001"},{"issue":"1","key":"2021091807313134100_CIT0002","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S2213-8587(17)30186-9","article-title":"Type 2 diabetes in adolescents and young adults","volume":"6","author":"Lascar","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"7","key":"2021091807313134100_CIT0003","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2337\/dc19-1988","article-title":"Adolescent obesity and early-onset type 2 diabetes","volume":"43","author":"Twig","year":"2020","journal-title":"Diabetes Care."},{"key":"2021091807313134100_CIT0004","first-page":"2011","article-title":"Current asthma prevalence by weight status among adults\u202f: NCHS Data Brief [Internet]","author":"Akinbami","year":"2016"},{"key":"2021091807313134100_CIT0005","first-page":"1426","article-title":"Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016-results from three population surveys","volume-title":"Clin Exp Allergy","author":"Backman","year":"2017"},{"issue":"3","key":"2021091807313134100_CIT0006","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.diabres.2010.09.010","article-title":"Asthma, chronic obstructive pulmonary disease, and type 2 diabetes in the Women\u2019s Health Study","volume":"90","author":"Song","year":"2010","journal-title":"Diabetes Res Clin Pract."},{"issue":"10","key":"2021091807313134100_CIT0007","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.2337\/diacare.27.10.2478","article-title":"Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women","volume":"27","author":"Rana","year":"2004","journal-title":"Diabetes Care."},{"issue":"2","key":"2021091807313134100_CIT0008","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.diabres.2012.11.019","article-title":"Asthma and the risk of type 2 diabetes in the Singapore Chinese Health Study","volume":"99","author":"Mueller","year":"2013","journal-title":"Diabetes Res Clin Pract."},{"issue":"12","key":"2021091807313134100_CIT0009","doi-asserted-by":"crossref","first-page":"877","DOI":"10.7326\/0003-4819-144-12-200606200-00004","article-title":"Autoimmune diseases in asthma","volume":"144","author":"Tirosh","year":"2006","journal-title":"Ann Intern Med."},{"issue":"1","key":"2021091807313134100_CIT0010","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2337\/dc19-1562","article-title":"Childhood pancreatitis and risk for incident diabetes in adulthood","volume":"43","author":"Bendor","year":"2020","journal-title":"Diabetes Care."},{"issue":"1","key":"2021091807313134100_CIT0011","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1183\/09031936.00138707","article-title":"Global strategy for asthma management and prevention: GINA executive summary","volume":"31","author":"Bateman","year":"2008","journal-title":"Eur Respir J."},{"key":"2021091807313134100_CIT0012","article-title":"(2021): Asthma & type 2 diabetes - Supplementary Appendix.pdf.","author":"Shapiro"},{"issue":"25","key":"2021091807313134100_CIT0013","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1056\/NEJMoa1503840","article-title":"Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood","volume":"374","author":"Twig","year":"2016","journal-title":"N Engl J Med."},{"issue":"11","key":"2021091807313134100_CIT0014","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.2337\/dc14-0715","article-title":"Cognitive function and the risk for diabetes among young men","volume":"37","author":"Twig","year":"2014","journal-title":"Diabetes Care."},{"issue":"7","key":"2021091807313134100_CIT0015","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1136\/jech.55.7.508","article-title":"A heuristic approach to the formulas for population attributable fraction","volume":"55","author":"Hanley","year":"2001","journal-title":"J Epidemiol Community Health."},{"key":"2021091807313134100_CIT0016","first-page":"1","volume-title":"Global asthma prevalence in adults: findings from the cross-sectional world health survey","author":"To","year":"2012"},{"issue":"4","key":"2021091807313134100_CIT0017","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/ijo.2017.263","article-title":"Body mass index and infectious disease mortality in midlife in a cohort of 2.3 million adolescents","volume":"42","author":"Twig","year":"2018","journal-title":"Int J Obes (Lond)."},{"issue":"4","key":"2021091807313134100_CIT0018","doi-asserted-by":"crossref","first-page":"e839","DOI":"10.1542\/peds.2010-3636","article-title":"Prevalence of asthma and its association with glycemic control among youth with diabetes","volume":"128","author":"Black","year":"2011","journal-title":"Pediatrics."},{"issue":"1","key":"2021091807313134100_CIT0019","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2337\/dc09-0880","article-title":"Patients diagnosed with diabetes are at increased risk for asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and pneumonia but not lung cancer","volume":"33","author":"Ehrlich","year":"2010","journal-title":"Diabetes Care."},{"issue":"4","key":"2021091807313134100_CIT0020","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/j.1398-9995.2010.02504.x","article-title":"Risk of asthma in adult twins with type 2 diabetes and increased body mass index","volume":"66","author":"Thomsen","year":"2011","journal-title":"Allergy."},{"issue":"4","key":"2021091807313134100_CIT0021","first-page":"300","article-title":"Hemoglobin a1c levels in children with asthma using low dose inhaled corticosteroids","volume":"46","author":"Yucel","year":"2009","journal-title":"Indian Pediatr."},{"issue":"11","key":"2021091807313134100_CIT0022","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/j.rmed.2012.07.011","article-title":"Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids","volume":"106","author":"O\u2019Byrne","year":"2012","journal-title":"Respir Med."},{"issue":"11","key":"2021091807313134100_CIT0023","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.amjmed.2010.06.019","article-title":"Inhaled corticosteroids and the risks of diabetes onset and progression","volume":"123","author":"Suissa","year":"2010","journal-title":"Am J Med."},{"issue":"8","key":"2021091807313134100_CIT0024","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1111\/dom.14040","article-title":"Use of inhaled corticosteroids and the risk of developing type 2 diabetes in patients with chronic obstructive pulmonary disease","volume":"22","author":"Saeed","year":"2020","journal-title":"Diabetes Obes Metab."},{"issue":"6","key":"2021091807313134100_CIT0025","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.2337\/dc18-2158","article-title":"Association between topical corticosteroid use and type 2 diabetes in two European population-based adult cohorts","volume":"42","author":"Andersen","year":"2019","journal-title":"Diabetes Care."},{"issue":"1","key":"2021091807313134100_CIT0026","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jaci.2017.04.009","article-title":"Oral corticosteroid exposure and adverse effects in asthmatic patients","volume":"141","author":"Sullivan","year":"2018","journal-title":"J Allergy Clin Immunol."},{"issue":"1-2","key":"2021091807313134100_CIT0027","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.mrfmmm.2009.09.005","article-title":"Chronic inflammation and asthma","volume":"690","author":"Murdoch","year":"2010","journal-title":"Mutat Res."},{"issue":"2","key":"2021091807313134100_CIT0028","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nri2925","article-title":"Type 2 diabetes as an inflammatory disease","volume":"11","author":"Donath","year":"2011","journal-title":"Nat Rev Immunol."},{"issue":"2","key":"2021091807313134100_CIT0029","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2337\/dc11-2298","article-title":"White blood cells count and incidence of type 2 diabetes in young men","volume":"36","author":"Twig","year":"2013","journal-title":"Diabetes Care."},{"issue":"7","key":"2021091807313134100_CIT0030","doi-asserted-by":"crossref","first-page":"e1001669","DOI":"10.1371\/journal.pmed.1001669","article-title":"Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study","volume":"11","author":"Granell","year":"2014","journal-title":"Plos Med."},{"issue":"3","key":"2021091807313134100_CIT0031","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/ije\/dyz070","article-title":"Elucidation of causal direction between asthma and obesity: a bi-directional Mendelian randomization study","volume":"48","author":"Xu","year":"2019","journal-title":"Int J Epidemiol."},{"issue":"10","key":"2021091807313134100_CIT0032","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.2337\/dc07-0413","article-title":"Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort","volume":"30","author":"Tso","year":"2007","journal-title":"Diabetes Care."},{"issue":"2","key":"2021091807313134100_CIT0033","doi-asserted-by":"crossref","first-page":"L227","DOI":"10.1152\/ajplung.00429.2017","article-title":"FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation","volume":"315","author":"Ge","year":"2018","journal-title":"Am J Physiol Lung Cell Mol Physiol."},{"key":"2021091807313134100_CIT0034","author":"Global initiative for asthma.","year":"2019"},{"key":"2021091807313134100_CIT0035","first-page":"1798","volume-title":"Type 2 diabetes in the young: the evolving epidemic. The International Diabetes Federation Consensus Workshop","author":"Alberti","year":"2004"},{"issue":"6","key":"2021091807313134100_CIT0036","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1177\/2040622314548679","article-title":"Early onset type 2 diabetes: risk factors, clinical impact and management","volume":"5","author":"Wilmot","year":"2014","journal-title":"Ther Adv Chronic Dis."},{"issue":"11","key":"2021091807313134100_CIT0037","doi-asserted-by":"crossref","first-page":"e0143084","DOI":"10.1371\/journal.pone.0143084","article-title":"Diabetes prevalence in Sweden at present and projections for year 2050","volume":"10","author":"Andersson","year":"2015","journal-title":"Plos One."},{"key":"2021091807313134100_CIT0038","author":"Tanamas","year":"2012"},{"key":"2021091807313134100_CIT0039","first-page":"1052","volume-title":"Trends in prevalence of symptoms of asthma, hay fever, and eczema in 12-14 year olds in the British Isles, 1995-2002: questionnaire survey","author":"Anderson","year":"2004"},{"issue":"5","key":"2021091807313134100_CIT0040","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.rmed.2014.02.011","article-title":"Trends in the prevalence of asthma, rhinitis, and eczema in 15 year old adolescents over an 8 year period","volume":"108","author":"Kim","year":"2014","journal-title":"Respir Med."},{"issue":"2","key":"2021091807313134100_CIT0041","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1183\/09031936.00194308","article-title":"Changes in the prevalence of asthma in adults since 1966: the Busselton health study","volume":"35","author":"James","year":"2010","journal-title":"Eur Respir J."},{"issue":"3","key":"2021091807313134100_CIT0042","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.jaci.2006.06.020","article-title":"The natural history of asthma","volume":"118","author":"Reed","year":"2006","journal-title":"J Allergy Clin Immunol."},{"issue":"6","key":"2021091807313134100_CIT0043","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.2337\/dc13-2101","article-title":"Estimating the delay between onset and diagnosis of type 2 diabetes from the time course of retinopathy prevalence","volume":"37","author":"Porta","year":"2014","journal-title":"Diabetes Care."},{"issue":"7303","key":"2021091807313134100_CIT0044","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature09103","article-title":"The genome-wide structure of the Jewish people","volume":"466","author":"Behar","year":"2010","journal-title":"Nature."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgab542\/40408006\/dgab542.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgab542\/40408006\/dgab542.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T07:32:05Z","timestamp":1631950325000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article\/doi\/10.1210\/clinem\/dgab542\/6325382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":44,"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgab542","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]},"article-number":"dgab542"}}