University of Oulu

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

Heterogeneity in the presentation of clinical type 1 diabetes defined by the level of risk conferred by human leukocyte antigen class II genotypes

Saved in:
Author: Taka, Antti-Mathias1,2; Härkönen, Taina1,2; Vähäsalo, Paula3,4;
Organizations: 1Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
3Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland
4Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
5Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
6Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
7Clinical Microbiology, Turku University Hospital, Turku, Finland
8Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe202201199448
Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2022-12-23
Description:

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.

see all

Series: Pediatric diabetes
ISSN: 1399-543X
ISSN-E: 1399-5448
ISSN-L: 1399-543X
Volume: 23
Issue: 2
Pages: 219 - 227
DOI: 10.1111/pedi.13300
OADOI: https://oadoi.org/10.1111/pedi.13300
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: 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.
Copyright information: © 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.