Screening of Diabetes-Associated Autoantibodies in First-Degree Relatives of Patients with Type 1 Diabetes

Project no. 32332 · Status: Kapanmış (Yayın bekleniyor) · 2024

Summary

<p><strong>Objective:</strong>&nbsp;We&nbsp;screened&nbsp;diabetes-associated&nbsp;autoantibodies&nbsp;in&nbsp;2–18-year-old&nbsp;first-degree&nbsp;relatives&nbsp;(FDRs)&nbsp;of&nbsp;individuals&nbsp;with&nbsp;type&nbsp;1&nbsp;diabetes&nbsp;in&nbsp;Türkiye&nbsp;to&nbsp;define&nbsp;prevalence&nbsp;and&nbsp;age&nbsp;distribution,&nbsp;identify&nbsp;determinants&nbsp;of&nbsp;autoantibody&nbsp;positivity,&nbsp;and&nbsp;quantify&nbsp;acute&nbsp;anxiety&nbsp;changes&nbsp;in&nbsp;children&nbsp;and&nbsp;parents&nbsp;following&nbsp;result&nbsp;disclosure.</p><p><strong>Research&nbsp;Design&nbsp;and&nbsp;Methods:</strong>&nbsp;In&nbsp;this&nbsp;multicenter&nbsp;cross-sectional&nbsp;study&nbsp;conducted&nbsp;across&nbsp;nine&nbsp;pediatric&nbsp;endocrinology&nbsp;centers&nbsp;in&nbsp;Türkiye,&nbsp;440&nbsp;FDRs&nbsp;aged&nbsp;2–18&nbsp;years&nbsp;were&nbsp;screened.&nbsp;Affected&nbsp;FDR&nbsp;relationships&nbsp;included&nbsp;an&nbsp;affected&nbsp;sister&nbsp;(n&nbsp;=&nbsp;206),&nbsp;brother&nbsp;(n&nbsp;=&nbsp;204),&nbsp;mother&nbsp;(n&nbsp;=&nbsp;22),&nbsp;and&nbsp;father&nbsp;(n&nbsp;=&nbsp;13).&nbsp;ZnT8,&nbsp;GAD,&nbsp;insulin&nbsp;autoantibody&nbsp;(IAA),&nbsp;and&nbsp;IA-2&nbsp;autoantibodies&nbsp;were&nbsp;measured&nbsp;by&nbsp;ELISA;&nbsp;perinatal&nbsp;variables&nbsp;including&nbsp;gestational&nbsp;age&nbsp;were&nbsp;recorded.&nbsp;In&nbsp;the&nbsp;8–18-year&nbsp;subsample,&nbsp;child&nbsp;anxiety&nbsp;was&nbsp;assessed&nbsp;using&nbsp;the&nbsp;full&nbsp;Screen&nbsp;for&nbsp;Child&nbsp;Anxiety&nbsp;Related&nbsp;Emotional&nbsp;Disorders&nbsp;(SCARED)&nbsp;and&nbsp;parental&nbsp;anxiety&nbsp;using&nbsp;the&nbsp;State–Trait&nbsp;Anxiety&nbsp;Inventory&nbsp;(STAI-I/II),&nbsp;administered&nbsp;pre-screening&nbsp;and&nbsp;immediately&nbsp;after&nbsp;disclosure.</p><p><strong>Results:</strong>&nbsp;Autoantibody&nbsp;positivity&nbsp;was&nbsp;16.4%&nbsp;(72/440),&nbsp;and&nbsp;multiple&nbsp;autoantibodies&nbsp;were&nbsp;detected&nbsp;in&nbsp;3.0%&nbsp;(13/440).&nbsp;Among&nbsp;445&nbsp;affected&nbsp;FDR&nbsp;relationships,&nbsp;92.1%&nbsp;were&nbsp;sibling-based&nbsp;and&nbsp;7.9%&nbsp;parent-based.&nbsp;ZnT8&nbsp;was&nbsp;most&nbsp;common&nbsp;(11.4%)&nbsp;and&nbsp;predominated&nbsp;at&nbsp;ages&nbsp;2–6&nbsp;years&nbsp;(82%&nbsp;of&nbsp;autoantibody-positive&nbsp;children),&nbsp;declining&nbsp;with&nbsp;age.&nbsp;ZnT8-positive&nbsp;participants&nbsp;were&nbsp;younger&nbsp;than&nbsp;ZnT8-negative&nbsp;participants&nbsp;(7.9&nbsp;±&nbsp;4.6&nbsp;vs&nbsp;10.0&nbsp;±&nbsp;4.5&nbsp;years;&nbsp;p=0.002).&nbsp;Each&nbsp;additional&nbsp;week&nbsp;of&nbsp;gestational&nbsp;age&nbsp;was&nbsp;associated&nbsp;with&nbsp;lower&nbsp;odds&nbsp;of&nbsp;autoantibody&nbsp;positivity&nbsp;(aOR&nbsp;0.80&nbsp;per&nbsp;week;&nbsp;95%&nbsp;CI&nbsp;0.68–0.93;&nbsp;p=0.005).&nbsp;This&nbsp;association&nbsp;persisted&nbsp;and&nbsp;was&nbsp;strengthened&nbsp;after&nbsp;exclusion&nbsp;of&nbsp;participants&nbsp;with&nbsp;an&nbsp;affected&nbsp;mother&nbsp;(aOR&nbsp;0.71&nbsp;per&nbsp;week;&nbsp;95%&nbsp;CI&nbsp;0.59–0.85;&nbsp;p&lt;0.001).&nbsp;SCARED&nbsp;increased&nbsp;after&nbsp;disclosure&nbsp;in&nbsp;autoantibody-positive&nbsp;children&nbsp;(d=1.31;&nbsp;p&lt;0.001)&nbsp;but&nbsp;decreased&nbsp;in&nbsp;autoantibody-negative&nbsp;children&nbsp;(d=0.62;&nbsp;p&lt;0.001).&nbsp;Parental&nbsp;anxiety&nbsp;increased&nbsp;after&nbsp;positive&nbsp;results&nbsp;(state&nbsp;d=2.19;&nbsp;p&lt;0.001;&nbsp;trait&nbsp;d=0.69;&nbsp;p=0.001)&nbsp;and&nbsp;decreased&nbsp;after&nbsp;negative&nbsp;results&nbsp;(p&lt;0.001).</p><p><strong>Conclusions:</strong>&nbsp;ZnT8&nbsp;predominance&nbsp;in&nbsp;early&nbsp;childhood&nbsp;and&nbsp;the&nbsp;independent&nbsp;association&nbsp;of&nbsp;gestational&nbsp;age&nbsp;with&nbsp;autoantibody&nbsp;positivity&nbsp;support&nbsp;integrating&nbsp;age&nbsp;and&nbsp;perinatal&nbsp;history&nbsp;into&nbsp;presymptomatic&nbsp;risk&nbsp;stratification.&nbsp;These&nbsp;findings&nbsp;should&nbsp;be&nbsp;interpreted&nbsp;primarily&nbsp;in&nbsp;the&nbsp;context&nbsp;of&nbsp;a&nbsp;sibling-dominant&nbsp;pediatric&nbsp;FDR&nbsp;screening&nbsp;cohort.&nbsp;The&nbsp;marked,&nbsp;outcome-dependent&nbsp;anxiety&nbsp;response&nbsp;indicates&nbsp;that&nbsp;screening&nbsp;programmes&nbsp;should&nbsp;pair&nbsp;immunological&nbsp;testing&nbsp;with&nbsp;structured,&nbsp;result-specific&nbsp;counseling,&nbsp;integrating&nbsp;psychological&nbsp;support&nbsp;protocols&nbsp;that&nbsp;address&nbsp;differential&nbsp;parent–child&nbsp;anxiety&nbsp;responses&nbsp;with&nbsp;child-appropriate&nbsp;assessment.</p><p><strong>Keywords:</strong>&nbsp;Diabetes&nbsp;Mellitus,&nbsp;Type&nbsp;1;&nbsp;First-Degree&nbsp;Relatives;&nbsp;Autoantibodies;&nbsp;Zinc&nbsp;Transporter&nbsp;8;&nbsp;Gestational&nbsp;Age;&nbsp;Anxiety;&nbsp;Child;&nbsp;Parents;&nbsp;Screening;&nbsp;Siblings&nbsp;</p>

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