Heterogeneity in the presentation of clinical type 1 diabetes defined by the level of risk conferred by human leukocyte antigen class II genotypes
Taka, Antti-Mathias; Härkönen, Taina; Vähäsalo, Paula; Lempainen, Johanna; Veijola, Riitta; Ilonen, Jorma; Knip, Mikael; the Finnish Pediatric Diabetes Register (2021-12-23)
Taka, A-M, Härkönen, T, Vähäsalo, P, et al. Heterogeneity in the presentation of clinical type 1 diabetes defined by the level of risk conferred by human leukocyte antigen class II genotypes. Pediatr Diabetes. 2022; 23(2): 219- 227. doi:10.1111/pedi.13300
© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Taka, A-M, Härkönen, T, Vähäsalo, P, et al. Heterogeneity in the presentation of clinical type 1 diabetes defined by the level of risk conferred by human leukocyte antigen class II genotypes. Pediatr Diabetes. 2022; 23( 2): 219- 227, which has been published in final form at https://doi.org/10.1111/pedi.13300. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
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https://urn.fi/URN:NBN:fi-fe202201199448
Tiivistelmä
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.
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