{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:09:07Z","timestamp":1777356547909,"version":"3.51.4"},"reference-count":37,"publisher":"American Diabetes Association","issue":"4","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,4,1]]},"abstract":"<jats:p>OBJECTIVE\u2014To investigate the prevalence of autoimmune diseases in young patients (probands) with type 1 diabetes and their first-degree relatives, and to determine the spectrum of extrapancreatic manifestations in these subjects.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014The study population included 109 probands age 13 \u00b1 4.9 years and 412 first-degree relatives age 28.7 \u00b1 16.2 years. The prevalence rates of autoimmune thyroiditis and celiac disease were determined in all probands and in 100 of the 412 first-degree relatives. Control groups included 78 subjects age 14.9 \u00b1 10.4 years for the prevalence of autoimmune thyroiditis and 120,000 youth ages 16\u201317 years for the prevalence of celiac disease. Thyroiditis and celiac disease were diagnosed by abnormally high thyroid peroxidase (TPO), thyroglobulin (TG), antigliadin, and antiendomysial antibody titers. Celiac was confirmed by biopsy. A questionnaire was used to interview probands and relatives to determine the spectrum of autoimmune manifestations.<\/jats:p>\n               <jats:p>RESULTS\u2014The prevalence of autoimmune thyroiditis determined by high TPO and\/or TG titers was 27 and 25% for probands and relatives, respectively. These rates were higher than those for control subjects (P &amp;lt; 000.1). The prevalence of celiac disease among probands and screened relatives was 8.3 and 6%, respectively. These rates were higher than those for control subjects and the 312 family members interviewed only (0.1 and 0.3%, respectively; P &amp;lt; 0.0001). Interviews of participants revealed a wide range of associated autoimmune diseases. The risk of developing an autoimmune disease was higher (P &amp;lt; 0.001) in families with a proband who had an additional autoimmune manifestation.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014Screening for autoimmune thyroiditis and celiac disease should be performed in patients with type 1 diabetes and their first-degree relatives, especially when the probands have an additional autoimmune manifestation.<\/jats:p>","DOI":"10.2337\/diacare.26.4.1235","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T22:51:27Z","timestamp":1173135087000},"page":"1235-1240","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":64,"title":["Extrapancreatic Autoimmune Manifestations in Type 1 Diabetes Patients and Their First-Degree Relatives"],"prefix":"10.2337","volume":"26","author":[{"given":"Aaron","family":"Hanukoglu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avraam","family":"Mizrachi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilan","family":"Dalal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osnat","family":"Admoni","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Haemek Medical Center, Afula, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yardena","family":"Rakover","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Haemek Medical Center, Afula, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zvy","family":"Bistritzer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Assaf Harofeh Medical Center, Zerifin, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arie","family":"Levine","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eli","family":"Somekh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam","family":"Tuval","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Boaz","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avraham","family":"Golander","sequence":"additional","affiliation":[{"name":"Dana Children\u2019s Hospital, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031216155207100_R1","doi-asserted-by":"crossref","unstructured":"Slover RH, Eisenbarth GS: Prevention of type I diabetes and recurrent B-cell destruction of transplanted Islets. Endocr Rev\u200818:241\u2013258, 1997","DOI":"10.1210\/edrv.18.2.0299"},{"key":"2022031216155207100_R2","doi-asserted-by":"crossref","unstructured":"Riley WJ, Maclaren WJ, Lezotte DC, Spillar RP, Rosenbloom AL: Thyroid autoimmunity in insulin-dependent diabetes mellitus: the case for routine screening. J Pediatr\u200899:350\u2013354, 1981","DOI":"10.1016\/S0022-3476(81)80316-2"},{"key":"2022031216155207100_R3","doi-asserted-by":"crossref","unstructured":"McKenna MJ, Hershkowitz R, Wolfsdorf JI: Screening for thyroid disease in children with IDDM. Diabetes Care\u200813:801\u2013803, 1990","DOI":"10.2337\/diacare.13.7.801"},{"key":"2022031216155207100_R4","doi-asserted-by":"crossref","unstructured":"Burek CL, Rose NR, Guire KE, Hoffman WH: Thyroid autoantibodies in black and white children and adolescents with type 1 diabetes mellitus and their first degree relatives. Autoimmunity\u20087:157\u2013167, 1990","DOI":"10.3109\/08916939008993388"},{"key":"2022031216155207100_R5","doi-asserted-by":"crossref","unstructured":"Lorini R, d\u2019Annunzio G, Vitali L, Scaramuzza A: IDDM and autoimmune thyroid disease in the pediatric age group. J Pediatr Endocrinol Metab\u20089(Suppl. 1):89\u201394, 1996","DOI":"10.1515\/JPEM.1996.9.S1.89"},{"key":"2022031216155207100_R6","unstructured":"Maugendre D, Massart C, Karacatsanis C, Guilhem I, Poirier JY, Sonnet E, Allanic H: Increased prevalence of thyroid autoantibodies and subclinical thyroid failure in relatives of patients with overt endocrine disease-associated diabetes but not type 1 diabetes alone. Diabetes Metab\u200823:302\u2013307, 1997"},{"key":"2022031216155207100_R7","doi-asserted-by":"crossref","unstructured":"Lindberg B, Ericsson UB, Ljung R, Ivarsson SA: High prevalence of thyroid autoantibodies at diagnosis of insulin-dependent diabetes mellitus in Swedish children. J Lab Clin Med\u2008130:585\u2013589, 1997","DOI":"10.1016\/S0022-2143(97)90108-6"},{"key":"2022031216155207100_R8","doi-asserted-by":"crossref","unstructured":"Chang CC, Huang CN, Chuang LM: Autoantibodies to thyroid peroxidase in patients with type 1 diabetes in Taiwan. Eur J Endocrinol\u2008139:44\u201348, 1998","DOI":"10.1530\/eje.0.1390044"},{"key":"2022031216155207100_R9","doi-asserted-by":"crossref","unstructured":"McCanlies E, O\u2019Leary LA, Foley TP, Kramer MK, Burke JP, Libman, Swan JS, Steenkiste AR, McCarthy BJ, Trucco M, Dorman JS: Hashimoto thyroiditis and insulin-dependent diabetes mellitus: differences among individuals with and without abnormal thyroid function. J Clin Endocrinol Metab\u200883:1548\u20131551, 1998","DOI":"10.1210\/jcem.83.5.4769"},{"key":"2022031216155207100_R10","unstructured":"Roldan MB, Alonso M, Barrio R: Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Diabetes Nutr Metab\u200812:27\u201331, 1999"},{"key":"2022031216155207100_R11","doi-asserted-by":"crossref","unstructured":"Verge CF, Howard NJ, Rowley MJ, Mackay IR, Zimmet PZ, Egan M, Hulinska H, Hulinsky I, Silvestrini RA, Kamath S, et al: Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population based study. Diabetologia\u200837:1113\u20131120, 1994","DOI":"10.1007\/BF00418375"},{"key":"2022031216155207100_R12","doi-asserted-by":"crossref","unstructured":"Calero P, Ribes-Koninckx C, Albiach V, Carles C, Ferrer J: IgA antigliadin antibodies as a screening method for nonovert celiac disease in children with insulin dependent diabetes mellitus. J Pediatr Gastroenterol Nutr\u200823:29\u201333, 1996","DOI":"10.1097\/00005176-199607000-00006"},{"key":"2022031216155207100_R13","doi-asserted-by":"crossref","unstructured":"Acerini CL, Ahmed ML, Ross KM, Sullivan PB, Bird G, Dunger DB: Coeliac disease in children and adolescents with IDDM: clinical characteristics and response to gluten-free diet. Diabet Med\u200815:38\u201344, 1998","DOI":"10.1002\/(SICI)1096-9136(199801)15:1<38::AID-DIA520>3.0.CO;2-L"},{"key":"2022031216155207100_R14","doi-asserted-by":"crossref","unstructured":"Vitoria JC, Castano L, Rica I, Bilbao JR, Arrieta A, Garcia-Masdevall MD: Association of insulin-dependent diabetes mellitus and celiac disease: a study based on serologic markers. J Pediatr Gastroenterol Nutr\u200827:47\u201352, 1998","DOI":"10.1097\/00005176-199807000-00008"},{"key":"2022031216155207100_R15","doi-asserted-by":"crossref","unstructured":"Fraser-Reynolds KA, Butzner JD, Stephure DK, Trussell RA, Scott RB: Use of immunoglobulin A-antiendomysial antibody to screen for celiac disease in North American children with type 1 diabetes. Diabetes Care\u200821:1985\u20131989, 1998","DOI":"10.2337\/diacare.21.11.1985"},{"key":"2022031216155207100_R16","doi-asserted-by":"crossref","unstructured":"Carlsson AK, Axelsson IEM, Borulf SK, Bredberg ACA, LindbergBA, Sjoberg KG, Ivarsson S-A: Prevalence of IgA-antiendomysium and IgA-antigliadin autoantibodies at diagnosis of insulin-dependent diabetes mellitus in Swedish children and adolescents. Pediatrics\u2008103:1248\u20131252, 1999","DOI":"10.1542\/peds.103.6.1248"},{"key":"2022031216155207100_R17","doi-asserted-by":"crossref","unstructured":"Parnell N, Ciclitira PJ: Celiac disease. Curr Opin Gastroenterol\u200815:120\u2013124, 1999","DOI":"10.1097\/00001574-199903000-00006"},{"key":"2022031216155207100_R18","doi-asserted-by":"crossref","unstructured":"Jaeger C, Petzoldt R, Hatziagelaki E, Bretzel RG: Comparative analysis of organ-specific autoantibodies and celiac disease-associated antibodies in type 1 diabetic patients, their first-degree relatives, and healthy control subjects. Diabetes Care\u200824:27\u201332, 2001","DOI":"10.2337\/diacare.24.1.27"},{"key":"2022031216155207100_R19","doi-asserted-by":"crossref","unstructured":"Fialkow PJ, Zavala C, Nielsen R: Thyroid autoimmunity: increased frequency in relatives of insulin-dependent diabetes patients. Ann Intern Med\u200883:170\u2013176, 1975","DOI":"10.7326\/0003-4819-83-2-170"},{"key":"2022031216155207100_R20","doi-asserted-by":"crossref","unstructured":"Bottazzo GF, Mann JI, Thorogood M, Baum JD, Doniach D: Autoimmunity in juvenile diabetics and their families. BMJ\u20082:165\u2013168, 1978","DOI":"10.1136\/bmj.2.6131.165"},{"key":"2022031216155207100_R21","doi-asserted-by":"crossref","unstructured":"Betterle C, Zanette F, Pedini B, Presotto F, Rapp LB, Monciotti CM, Rigon F: Clinical and subclinical organ-specific autoimmune manifestations in type 1 (insulin dependent) diabetic patients and their first-degree relatives. Diabetologia\u200826:431\u2013436, 1984","DOI":"10.1007\/BF00262215"},{"key":"2022031216155207100_R22","doi-asserted-by":"crossref","unstructured":"Hagglof B, Rabinovitch A, Mackay P, Huen A, Rubenstein AH, Marner B, Nerup J, Lernmark A: Islet cell and other organ-specific autoantibodies in healthy first-degree relatives to insulin-dependent. Acta Paediatr Scand\u200875:611\u2013618, 1986","DOI":"10.1111\/j.1651-2227.1986.tb10260.x"},{"key":"2022031216155207100_R23","doi-asserted-by":"crossref","unstructured":"Boudraa G, Hachelaf W, Benbouabdellah M, Belkadi M, Benmanssour FZ, Touhami M: Prevalence of coeliac disease in diabetic children and their first-degree relatives in west Algeria: screening with serologic markers. Acta Paediatr Suppl\u2008412:58\u201360, 1996","DOI":"10.1111\/j.1651-2227.1996.tb14254.x"},{"key":"2022031216155207100_R24","doi-asserted-by":"crossref","unstructured":"Williams AJK, Norcross AJ, Lock RJ, Unsworth DJ, Gale EAM, Bingley PJ: The high prevalence of autoantibodies to tissue transglutaminase in first-degree relatives of patients with type 1 diabetes is not associated with islet autoimmunity. Diabetes Care\u200824:504\u2013509, 2001","DOI":"10.2337\/diacare.24.3.504"},{"key":"2022031216155207100_R25","doi-asserted-by":"crossref","unstructured":"Shamir R, Lerner A, Shinar E, Lahat N, Sobel E, Bar-or R, Kerner H, Eliakim R: The use of a single serological marker underestimates the prevalence of celiac disease in Israel: a study of blood donors. Am J Gastroenterology\u200897:2589\u20132594, 2002","DOI":"10.1111\/j.1572-0241.2002.06028.x"},{"key":"2022031216155207100_R26","doi-asserted-by":"crossref","unstructured":"Fasano A, Catassi C: Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology\u2008120:636\u2013651, 2001","DOI":"10.1053\/gast.2001.22123"},{"key":"2022031216155207100_R27","doi-asserted-by":"crossref","unstructured":"Dayan CM, Daniels GH: Chronic autoimmune thyroiditis. N Engl J Med\u2008335:99\u2013107, 1996","DOI":"10.1056\/NEJM199607113350206"},{"key":"2022031216155207100_R28","doi-asserted-by":"crossref","unstructured":"Barera G, Bonfanti R, Viscardi M, Bazzigaluppi E, Calori G, Meschi F, Bianchi C, Chiumello G: Occurrence of celiac disease after onset of type 1 diabetes: a 6-year prospective longitudinal study. Pediatrics\u2008109:833\u2013838, 2002","DOI":"10.1542\/peds.109.5.833"},{"key":"2022031216155207100_R29","unstructured":"Kontiainen S, Schlenzka A, Koskimies S, Rilva A, Maenpaa J: Autoantibodies and autoimmune diseases in young diabetics. Diabetes Res\u200813:151\u2013156, 1990"},{"key":"2022031216155207100_R30","doi-asserted-by":"crossref","unstructured":"Lagerqvist C, Ivarsson A, Juto P, Persson LA, Hernell O: Screening for adult coeliac disease: which serological marker(s) to use? J Intern Med\u2008250:241\u2013248, 2001","DOI":"10.1046\/j.1365-2796.2001.00891.x"},{"key":"2022031216155207100_R31","doi-asserted-by":"crossref","unstructured":"Hummel M, Bonifacio E, Stern M, Dittler J, Schimmel A, Ziegler AG: Development of celiac disease associated antibodies in offspring of parents with type I diabetes. Diabetologia\u200843:1005\u20131011, 2000","DOI":"10.1007\/s001250051483"},{"key":"2022031216155207100_R32","doi-asserted-by":"crossref","unstructured":"Saukkonen T, Ilonen J, Akerblom HK, Savilahti E: Prevalence of coeliac disease in siblings of patients with type I diabetes is related to the prevalence DQB1*02 allele. Diabetologia\u200844:1051\u20131053, 2001","DOI":"10.1007\/s001250100591"},{"key":"2022031216155207100_R33","doi-asserted-by":"crossref","unstructured":"Corrao G, Corazza GR, Bagnardi V, Brusco G, Ciacci C, Cottone M, Sategna Guidetti C, Usai P, Cesari P, Pelli MA, Loperfido S, Volta U, Calabro A, Certo M, the Club del Tenue Study Group: Mortality in patients with coeliac disease and their relatives: a cohort study. Lancet\u2008358:356\u2013361, 2001","DOI":"10.1016\/S0140-6736(01)05554-4"},{"key":"2022031216155207100_R34","doi-asserted-by":"crossref","unstructured":"Counsell CE, Taha A, Ruddell WS: Coeliac disease and autoimmune thyroid disease. Gut\u200835:844\u2013846, 1995","DOI":"10.1136\/gut.35.6.844"},{"key":"2022031216155207100_R35","doi-asserted-by":"crossref","unstructured":"Dalal I, Levine A, Somekh E, Mizrahi A, Hanukoglu A: Chronic urticaria in children: expanding the \u201cautoimmune kaleidoscope.\u201d Pediatrics\u2008106:1139\u20131141, 2000","DOI":"10.1542\/peds.106.5.1139"},{"key":"2022031216155207100_R36","doi-asserted-by":"crossref","unstructured":"Thorsby E, Undlien D: The HLA associated predisposition to type 1 diabetes and other autoimmune diseases. J Pediatr Endocrinol Metab\u20089:75\u201388, 1996","DOI":"10.1515\/JPEM.1996.9.S1.75"},{"key":"2022031216155207100_R37","doi-asserted-by":"crossref","unstructured":"Wandstrat A, Wakeland E: The genetics of complex autoimmune disease: non-MHC susceptibility genes (Review). Nat Immunol\u20082:802\u2013809, 2001","DOI":"10.1038\/ni0901-802"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/26\/4\/1235\/659563\/dc0403001235.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/26\/4\/1235\/659563\/dc0403001235.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T16:39:32Z","timestamp":1647103172000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/26\/4\/1235\/23726\/Extrapancreatic-Autoimmune-Manifestations-in-Type"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4,1]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,4,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diacare.26.4.1235","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4,1]]}}}