Title: Heterogeneity in the presentation of clinical type 1 diabetes defined by the level of risk conferred by human leukocyte antigen class II genotypes
Abstract: Pediatric DiabetesVolume 23, Issue 2 p. 219-227 PATHOPHYSIOLOGY AND PREVENTION Heterogeneity in the presentation of clinical type 1 diabetes defined by the level of risk conferred by human leukocyte antigen class II genotypes Antti-Mathias Taka, Antti-Mathias Taka orcid.org/0000-0002-1970-4978 Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, FinlandSearch for more papers by this authorTaina Härkönen, Taina Härkönen Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, FinlandSearch for more papers by this authorPaula Vähäsalo, Paula Vähäsalo orcid.org/0000-0002-2712-3903 Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland Department of Children and Adolescents, Oulu University Hospital, Oulu, FinlandSearch for more papers by this authorJohanna Lempainen, Johanna Lempainen Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland Clinical Microbiology, Turku University Hospital, Turku, FinlandSearch for more papers by this authorRiitta Veijola, Riitta Veijola orcid.org/0000-0002-6557-270X Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland Department of Children and Adolescents, Oulu University Hospital, Oulu, FinlandSearch for more papers by this authorJorma Ilonen, Jorma Ilonen orcid.org/0000-0002-9973-2062 Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, FinlandSearch for more papers by this authorMikael Knip, Corresponding Author Mikael Knip [email protected] orcid.org/0000-0003-0474-0033 Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland Correspondence Mikael Knip, University of Helsinki, Biomedicum 1, Haartmaninkatu 8, 00290 Helsinki, Finland. Email: [email protected] for more papers by this authorthe Finnish Pediatric Diabetes Register, the Finnish Pediatric Diabetes RegisterSearch for more papers by this author Antti-Mathias Taka, Antti-Mathias Taka orcid.org/0000-0002-1970-4978 Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, FinlandSearch for more papers by this authorTaina Härkönen, Taina Härkönen Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, FinlandSearch for more papers by this authorPaula Vähäsalo, Paula Vähäsalo orcid.org/0000-0002-2712-3903 Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland Department of Children and Adolescents, Oulu University Hospital, Oulu, FinlandSearch for more papers by this authorJohanna Lempainen, Johanna Lempainen Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland Clinical Microbiology, Turku University Hospital, Turku, FinlandSearch for more papers by this authorRiitta Veijola, Riitta Veijola orcid.org/0000-0002-6557-270X Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland Department of Children and Adolescents, Oulu University Hospital, Oulu, FinlandSearch for more papers by this authorJorma Ilonen, Jorma Ilonen orcid.org/0000-0002-9973-2062 Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, FinlandSearch for more papers by this authorMikael Knip, Corresponding Author Mikael Knip [email protected] orcid.org/0000-0003-0474-0033 Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland Correspondence Mikael Knip, University of Helsinki, Biomedicum 1, Haartmaninkatu 8, 00290 Helsinki, Finland. Email: [email protected] for more papers by this authorthe Finnish Pediatric Diabetes Register, the Finnish Pediatric Diabetes RegisterSearch for more papers by this author First published: 11 December 2021 https://doi.org/10.1111/pedi.13300 A complete list of the investigators for the Finnish Pediatric Diabetes Register and Sample Repository is found in the Appendix. Funding information: This study was supported by the Academy of Finland (Decision No 292538), Helsinki University Hospital Research Funds, Sigrid Juselius Foundation, Finska Läkaresällskapet, and Medicinska understödsföreningen Liv och Hälsa. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Objectives The association between human leukocyte antigen (HLA) class II genotypes and susceptibility to type 1 diabetes (T1D) is well established. This study aimed at examining whether there are differences in the presentation of T1D depending on the HLA genotype. Research Design and Methods We divided the study participants (N = 5798) in the Finnish Pediatric Diabetes Register into two groups based on the T1D risk conferred by their HLA genotype (high and moderate-risk genotypes, Group 1 vs. other genotypes, Group 2). We then examined differences in clinical, metabolic, and immunological characteristics. Children included in the study were 0–14-year-old and diagnosed between January 2003 and December 2019. Results Participants in Group 1 were younger at the time of diagnosis (P < 0.001) and had more frequently family members affected by T1D (P < 0.001). Diabetic ketoacidosis (DKA) was more frequent among participants in Group 2 (P = 0.014) who also had a longer duration of symptoms before diagnosis (P < 0.001) and higher hemoglobin A1c (P = 0.001) at diagnosis. The HLA genotype was not, however, directly related to the DKA frequency. The frequency of islet cell antibodies (P < 0.003), insulin autoantibodies (P < 0.001), and islet antigen 2 autoantibodies (P < 0.001) was higher in Group 1 whereas glutamic acid decarboxylase autoantibodies were more frequent (P < 0.001) in Group 2. Group 1 had more participants with multiple autoantibodies (P = 0.027) whereas antibody negativity was more frequent in Group 2 (P = 0.003). Conclusions These findings indicate disease heterogeneity in relation to both clinical disease presentation and humoral autoimmunity, in particular. This heterogeneity is, at least partly, defined by HLA Class II genotypes. CONFLICT OF INTEREST The authors declare no potential conflict of interest. Open Research DATA AVAILABILITY STATEMENT The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Volume23, Issue2March 2022Pages 219-227 RelatedInformation