{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:35Z","timestamp":1785473975623,"version":"3.56.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003010","name":"Ege \u00dcniversitesi","doi-asserted-by":"publisher","award":["32332-Multidisciplinary Priority Area Research Pro"],"award-info":[{"award-number":["32332-Multidisciplinary Priority Area Research Pro"]}],"id":[{"id":"10.13039\/501100003010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003010","name":"Ege University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003010","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/objective<\/jats:title>\n                    <jats:p>We screened 2\u201318-year-old first-degree relatives (FDRs) of individuals with type 1 diabetes in Turkey for diabetes-associated autoantibodies to define their prevalence and age distribution, to identify determinants of autoantibody positivity, and to quantify acute anxiety changes in children and parents after result disclosure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this multicentre cross-sectional study conducted across nine paediatric endocrinology centres in Turkey, 440 FDRs aged 2\u201318 years were screened. Affected FDR relationships included an affected sister (\n                      <jats:italic>n<\/jats:italic>\n                      =206), brother (\n                      <jats:italic>n<\/jats:italic>\n                      =204), mother (\n                      <jats:italic>n<\/jats:italic>\n                      =22) and father (\n                      <jats:italic>n<\/jats:italic>\n                      =13). ZnT8A, GADA, IAA and IA-2A autoantibodies were measured by ELISA; perinatal variables including gestational age were recorded. In the 8\u201318-year-old subsample, child anxiety was assessed using the full Screen for Child Anxiety Related Emotional Disorders (SCARED) and parental anxiety for these children was assessed using the State\u2013Trait Anxiety Inventory (STAI-I\/II), administered before screening and immediately after disclosure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The proportion of participants who were autoantibody-positive was 16.4% (72\/440), and multiple autoantibodies were detected in 13 individuals (3.0%). Among 445 affected FDR relationships, 92.1% were sibling-based and 7.9% were parent-based. ZnT8A was the most common autoantibody (11.4%) and predominated at ages 2\u20136 years (82% of autoantibody-positive children), declining with age. ZnT8A positivity showed an age-dependent decline, with ZnT8A-positive participants being significantly younger than ZnT8A-negative participants (7.92 \u00b1 4.62 vs 10.00 \u00b1 4.54 years;\n                      <jats:italic>p<\/jats:italic>\n                      =0.002). Each additional week of gestational age was associated with lower odds of autoantibody positivity (adjusted OR 0.80 per week; 95% CI 0.68, 0.93;\n                      <jats:italic>p<\/jats:italic>\n                      =0.005). This association persisted and was strengthened after exclusion of participants with an affected mother (adjusted OR 0.71 per week; 95% CI 0.59, 0.85;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001). SCARED scores increased after disclosure in autoantibody-positive children (\n                      <jats:italic>d<\/jats:italic>\n                      =1.31;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001) but decreased in autoantibody-negative children (\n                      <jats:italic>d<\/jats:italic>\n                      =0.62;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001). Parental anxiety increased after positive results (state\n                      <jats:italic>d<\/jats:italic>\n                      =2.19;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001; trait\n                      <jats:italic>d<\/jats:italic>\n                      =0.69;\n                      <jats:italic>p<\/jats:italic>\n                      =0.001) and decreased after negative results (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>The ZnT8A predominance in early childhood and the independent association of gestational age with autoantibody positivity support integrating age and perinatal history into presymptomatic risk stratification. These findings should be interpreted primarily within the context of a sibling-dominant paediatric FDR screening cohort. The marked outcome-dependent anxiety response indicates that screening programmes should pair immunological testing with structured, result-specific counselling, integrating psychological support protocols that address differential parent\u2013child anxiety responses with child-appropriate assessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06783-6","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T16:57:10Z","timestamp":1782406630000},"page":"2432-2444","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autoantibody screening in children who are first-degree relatives of individuals with type 1 diabetes in a sibling-dominant cohort in Turkey: a multicentre study on prevalence, determinants and post-screening parent\u2013child anxiety"],"prefix":"10.1007","volume":"69","author":[{"given":"U\u011fur C.","family":"Y\u0131lmaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-4404","authenticated-orcid":false,"given":"Deniz \u00d6.","family":"K\u0131z\u0131lay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem K.","family":"Kurt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130lkay B.","family":"Balaban Berber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130rem","family":"G\u00f6kdemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysun","family":"Ata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Erden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif G.","family":"Basa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6mer F.","family":"Yal\u00e7\u0131n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevim","family":"Onguner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanife G.","family":"Balk\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirmen K.","family":"\u00c7etin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samim","family":"\u00d6zen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnay","family":"Demir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze Y.","family":"Ba\u015f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Soylu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"An\u0131k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"G\u00fcrb\u00fcz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korcan","family":"Demir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zge","family":"K\u00f6pr\u00fcl\u00fc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selda A.","family":"Alt\u0131nc\u0131k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berna E.","family":"Filibeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcu","family":"\u00d6zbaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raika D.","family":"Onmu\u015f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damla","family":"G\u00f6k\u015fen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"issue":"10","key":"6783_CR1","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.2337\/dc15-1419","volume":"38","author":"RA Insel","year":"2015","unstructured":"Insel RA, Dunne JL, Atkinson MA et al (2015) Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. 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We also thank the Ege University Pediatric Endocrinology Research Laboratory team for technical support with autoantibody analyses, and the research nurses\/field staff for study coordination and data management. We also acknowledge the support of the Ege University Scientific Research Projects Coordination Unit.","order":1,"name":"Ethics","label":"Acknowledgements","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The datasets generated and analysed during the current study are not publicly available because they contain participant-level clinical and psychometric data from minors. De-identified data underlying the findings may be made available from the corresponding author upon reasonable request after publication and for 5 years thereafter, for non-commercial academic research with a methodologically sound proposal, subject to approval by the study investigators, and, where required, the relevant ethics committee and\/or institutional data-sharing procedures. Data may not be used to identify participants or shared with third parties.","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Open access funding provided by the Scientific and Technological Research Council of T\u00fcrkiye (T\u00dcB\u0130TAK). This study was supported by the Ege University Scientific Research Projects Coordination Unit (project no: 32332; Multidisciplinary Priority Area Research Project Program). No other external funding was received.","order":3,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","label":"Authors\u2019 relationships and activities","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"UCY conceived and designed the study, coordinated the multicentre protocol, curated the data, performed the analyses, and drafted the manuscript. D\u00d6K, DG and S\u00d6 contributed to study design and supervision, supported interpretation, and critically revised the manuscript. \u00d6KK, \u0130BB, \u0130G, AA, DE, EGB, \u00d6FY, S\u00d6, HGB, SK\u00c7, FG, KD, \u00d6K, SAA and BEF served as site investigators and were responsible for local implementation, recruitment, clinical characterisation and dataset verification. GYB and B\u00d6 developed and supervised the psychometric protocol, trained investigators, interpreted psychosocial outcomes, and reviewed the manuscript. MS and the Ege University laboratory team developed the autoantibody testing workflow, performed assays and quality control, and interpreted immunological data. RDO advised on epidemiological\/public health aspects and the analysis plan. DG supervised the study as senior author. D\u00d6K is the guarantor, had full access to all data and takes responsibility for data integrity, analytical accuracy, and completeness of reporting. All authors interpreted results, revised the manuscript, and approved the final version.","order":5,"name":"Ethics","label":"Contribution statement","group":{"name":"EthicsHeading","label":"Ethics"}}]}}