Witold Bauer1, Riitta Veijola2,3, Johanna Lempainen4,5,6, Minna Kiviniemi5, Taina Härkönen7,8, Jorma Toppari4,9, Mikael Knip7,8,10,11, Attila Gyenesei1,12, Jorma Ilonen5,6. 1. Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland. 2. Department of Paediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland. 3. Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland. 4. Department of Paediatrics, University of Turku and Turku University Hospital, Turku, Finland. 5. Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland. 6. Clinical Microbiology, Turku University Hospital, Turku, Finland. 7. Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 8. Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. 9. Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland. 10. Folkhälsan Research Center, Helsinki, Finland. 11. Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland. 12. Szentágothai Research Centre, University of Pécs, Pécs, Hungary.
Abstract
CONTEXT: Children with initial autoantibodies to either insulin (IAA) or glutamic acid decarboxylase (GADA) differ in peak age of seroconversion and have different type 1 diabetes (T1D) risk gene associations, suggesting heterogeneity in the disease process. OBJECTIVE: To compare the associations of age at seroconversion, HLA risk, and specificity of secondary autoantibodies with the progression of islet autoimmunity between children with either IAA or GADA as their first autoantibody. DESIGN AND METHODS: A cohort of 15,253 children with HLA-associated increased risk of T1D participated in a follow-up program in which islet autoantibodies were regularly measured. The median follow-up time was 6.7 years. Spearman correlation, Kaplan-Meier survival plots, and Cox proportional-hazard models were used for statistical analyses. RESULTS: Persistent positivity for at least one of the tested autoantibodies was detected in 998 children; 388 of children progressed to clinical T1D. Young age at initial seroconversion was associated with a high probability of expansion of IAA-initiated autoimmunity and progression to clinical diabetes, whereas expansion of GADA-initiated autoimmunity and progression to diabetes were not dependent on initial seroconversion age. The strength of HLA risk affected the progression of both IAA- and GADA-initiated autoimmunity. The simultaneous appearance of two other autoantibodies increased the rate of progression to diabetes compared with that of a single secondary autoantibody among subjects with GADA-initiated autoimmunity but not among those with IAA as the first autoantibody. CONCLUSIONS: Findings emphasize the differences in the course of islet autoimmunity initiated by either IAA or GADA supporting heterogeneity in the pathogenic process.
CONTEXT: Children with initial autoantibodies to either insulin (IAA) or glutamic acid decarboxylase (GADA) differ in peak age of seroconversion and have different type 1 diabetes (T1D) risk gene associations, suggesting heterogeneity in the disease process. OBJECTIVE: To compare the associations of age at seroconversion, HLA risk, and specificity of secondary autoantibodies with the progression of islet autoimmunity between children with either IAA or GADA as their first autoantibody. DESIGN AND METHODS: A cohort of 15,253 children with HLA-associated increased risk of T1D participated in a follow-up program in which islet autoantibodies were regularly measured. The median follow-up time was 6.7 years. Spearman correlation, Kaplan-Meier survival plots, and Cox proportional-hazard models were used for statistical analyses. RESULTS: Persistent positivity for at least one of the tested autoantibodies was detected in 998 children; 388 of children progressed to clinical T1D. Young age at initial seroconversion was associated with a high probability of expansion of IAA-initiated autoimmunity and progression to clinical diabetes, whereas expansion of GADA-initiated autoimmunity and progression to diabetes were not dependent on initial seroconversion age. The strength of HLA risk affected the progression of both IAA- and GADA-initiated autoimmunity. The simultaneous appearance of two other autoantibodies increased the rate of progression to diabetes compared with that of a single secondary autoantibody among subjects with GADA-initiated autoimmunity but not among those with IAA as the first autoantibody. CONCLUSIONS: Findings emphasize the differences in the course of islet autoimmunity initiated by either IAA or GADA supporting heterogeneity in the pathogenic process.
Authors: Kenney Ng; Vibha Anand; Harry Stavropoulos; Riitta Veijola; Jorma Toppari; Marlena Maziarz; Markus Lundgren; Kathy Waugh; Brigitte I Frohnert; Frank Martin; Olivia Lou; William Hagopian; Peter Achenbach Journal: Diabetologia Date: 2022-10-05 Impact factor: 10.460
Authors: Petra M Pöllänen; Samppa J Ryhänen; Jorma Toppari; Jorma Ilonen; Paula Vähäsalo; Riitta Veijola; Heli Siljander; Mikael Knip Journal: J Clin Endocrinol Metab Date: 2020-12-01 Impact factor: 5.958