ABSTRACT Objective: The aim of the study was to assess the autoimmunity in first degrees relatives (FDR) of patients with type 1 diabetes (T1DM) and the progression to T1DM after 10 years of follow up in the Brazilian population. Subjects and methods: Non-diabetic FDR of T1DM patients were interviewed and blood was drawn for autoantibodies measurement (GADA, IA-2A, IAA, ZnT8A). Serum samples were analyzed by standard radioligand binding assays performed at the Federal University of Rio de Janeiro (GADA, IAA and IA2A), and at the Skäne University Hospital, Sweden (ZnT8A). The FDR were interviewed by phone after 10 years to determine if they had developed T1DM. Descriptive statistical analysis was performed and results were described as means and standard deviation (SD). Results: 81 individuals were analyzed. Thirteen subjects had positive autoantibodies associated with T1DM.10 were positive for 1 autoantibody and 3 subjects were positive for multiple autoantibodies (1 of them showed positivity for 2 autoantibodies – GADA, ZnT8A – and the other two were positive for 3 autoantibodies – GADA, IA2A, ZnT8A). The 3 subjects with multiple positive autoantibodies developed T1DM within 10 years. Conclusions: In Brazilian FDR of T1DM patients, the positivity for multiple autoantibodies indicate a greater chance of progression to T1DM, similar to observed in Caucasians. ZnT8A was helpful in the risk assessment for T1DM development.

Objective Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and should be investigated annually in these individuals. The aim of this study was to evaluate the frequency of thyroid diseases in first degree relatives (FDR) of patients with T1DM. Subjects and methods Eighty individuals (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were measured in FDR. Results We found a similar prevalence of thyroid dysfunction in patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94). Conclusions Thyroid abnormalities seem to be common not only in patients with T1DM but also in their FDR, which suggests that screening strategies for thyroid diseases might also be useful to these individuals.

Objetivo Os autoanticorpos transportadores de zinco 8 (ZnT8A) foram pouco estudados em indivíduos não caucasianos. Nosso objetivo foi investigar a prevalência de autoanticorpos ZnT8 em pacientes com T1D e seus parentes de primeiro grau (PPG) em uma população multiétnica, assim como a sua relação com os polimorfismos genéticos da insulina (INS) ou proteína tirosina fosfatase não receptora tipo 22 (PTPN22). Sujeitos e métodos ZnT8A foram analisados no soro de pacientes com T1D (n = 72, idade média de 30,3 ± 11,4 anos) de duração variável (15,7 ± 11,8 anos) e seus PPG (n = 72, idade média de 30,3 ± 11,4 anos) usando-se um ensaio de competição com radioligantes (RBA) para variantes dos autoanticorpos ZnT8 (ZnT8-RWQ). Os polimorfismos de nucleotídeo único para a INS e PTPN22 foram genotipados. Resultados A prevalência de ZnT8A foi mais alta em pacientes T1D do que nos PPG, para ZnT8TriploA (24% contra 4%, p = 0,001), ZnT8RA (24% contra 4%, p < 0,001) e ZnT8QA (15% contra 3%, p = 0,004). Todos os PPG com ZnT8A (n = 3) apresentaram positividade para pelo menos outro anticorpo. A heterozigose para PTPN22 foi associada a uma frequência mais alta de ZnT8TriploA (p = 0,039) e de ZnT8RA (p = 0,038). Conclusões Os ZnT8A foram observados em pacientes não caucasianos com T1D, mesmo depois de anos do início da doença, assim como em seus PPG. Nos parentes, houve uma sobreposição entre os ZnT8A e outros anticorpos para T1D. Os ZnT8A mostraram-se associados aos polimorfismos PTPN22. São necessários outros estudos longitudinais para se elucidar a importância desses achados na história natural de pacientes com T1D com antecedentes étnicos variados.

Objective Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8 autoantibodies in patients with T1D and their first degree relatives (FDR) from a multiethnic population, as well as its relation with the insulin (INS) or the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms. Subjects and methods ZnT8A were analyzed in sera from T1D patients (n = 72, mean age of 30.3 ± 11.4 years) of variable duration (15.7 ± 11.8 years) and their FDR (n = 78, mean age of 18.3 ± 9.1 years) by a triple mix Radioligand Binding Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide polymorphism) for INS and PTPN22 were genotyped. Results The prevalence of ZnT8A was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001), ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22 was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p = 0.038). Conclusions ZnT8A is observed in non-Caucasian patients with T1D, even years after the disease onset, as well as in their FDR. In those, there was an overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22 polymorphisms. Further longitudinal studies are necessary to elucidate the importance of these findings in the natural history of T1D patients with multiethnic background.