PMID- 34894365
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20220310
IS  - 1399-5448 (Electronic)
IS  - 1399-543X (Linking)
VI  - 23
IP  - 2
DP  - 2022 Mar
TI  - Heterogeneity in the presentation of clinical type 1 diabetes defined by the 
      level of risk conferred by human leukocyte antigen class II genotypes.
PG  - 219-227
LID - 10.1111/pedi.13300 [doi]
AB  - 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.
CI  - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Taka, Antti-Mathias
AU  - Taka AM
AUID- ORCID: 0000-0002-1970-4978
AD  - Pediatric Research Center, Children's Hospital, University of Helsinki and 
      Helsinki University Hospital, Helsinki, Finland.
AD  - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki, Helsinki, Finland.
FAU - Harkonen, Taina
AU  - Harkonen T
AD  - Pediatric Research Center, Children's Hospital, University of Helsinki and 
      Helsinki University Hospital, Helsinki, Finland.
AD  - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki, Helsinki, Finland.
FAU - Vahasalo, Paula
AU  - Vahasalo P
AUID- ORCID: 0000-0002-2712-3903
AD  - Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, 
      University of Oulu, Oulu, Finland.
AD  - Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
FAU - Lempainen, Johanna
AU  - Lempainen J
AD  - Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, 
      Finland.
AD  - Department of Pediatrics, University of Turku and Turku University Hospital, 
      Turku, Finland.
AD  - Clinical Microbiology, Turku University Hospital, Turku, Finland.
FAU - Veijola, Riitta
AU  - Veijola R
AUID- ORCID: 0000-0002-6557-270X
AD  - Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, 
      University of Oulu, Oulu, Finland.
AD  - Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
FAU - Ilonen, Jorma
AU  - Ilonen J
AUID- ORCID: 0000-0002-9973-2062
AD  - Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, 
      Finland.
FAU - Knip, Mikael
AU  - Knip M
AUID- ORCID: 0000-0003-0474-0033
AD  - Pediatric Research Center, Children's Hospital, University of Helsinki and 
      Helsinki University Hospital, Helsinki, Finland.
AD  - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki, Helsinki, Finland.
AD  - Tampere Center for Child Health Research, Tampere University Hospital, Tampere, 
      Finland.
CN  - Finnish Pediatric Diabetes Register
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211223
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/*complications/genetics
MH  - Female
MH  - Finland
MH  - *Genetic Heterogeneity
MH  - Genotype
MH  - HLA Antigens/adverse effects/*genetics
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Logistic Models
MH  - Male
MH  - Registries/statistics & numerical data
OTO - NOTNLM
OT  - HLA class II genotypes
OT  - autoantibodies
OT  - children
OT  - heterogeneity
OT  - type 1 diabetes
EDAT- 2021/12/12 06:00
MHDA- 2022/03/11 06:00
CRDT- 2021/12/11 12:14
PHST- 2021/10/20 00:00 [revised]
PHST- 2021/08/11 00:00 [received]
PHST- 2021/11/30 00:00 [accepted]
PHST- 2021/12/12 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2021/12/11 12:14 [entrez]
AID - 10.1111/pedi.13300 [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2022 Mar;23(2):219-227. doi: 10.1111/pedi.13300. Epub 2021 Dec 
      23.