University of Oulu

Kuusela, S, Keskinen, P, Pokka, T, et al. Extended family history of type 1 diabetes in HLA‐predisposed children with and without islet autoantibodies. Pediatr Diabetes. 2020; 21: 1447– 1456.

Extended family history of type 1 diabetes in HLA‐predisposed children with and without islet autoantibodies

Saved in:
Author: Kuusela, Salla1,2,3; Keskinen, Päivi3,4; Pokka, Tytti1,2;
Organizations: 1Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland
2Department for Children and Adolescents, Medical Research Center, Oulu University Hospital, Oulu, Finland
3Department for Children and Adolescents, Tampere University Hospital, Tampere, Finland
4Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland
5Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
6Research Programs for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
7Folkhälsan Research Center, Helsinki, Finland
8Immunogenetics Laboratory, University of Turku, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
Persistent link:
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2021-01-22


Objective: The aim of this study was to explore the extended family history of type 1 diabetes in children at genetic risk and define the impact of a positive family history on the development of islet autoimmunity and type 1 diabetes.

Methods: The subjects were participants in The Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study and carried increased HLA‐conferred risk for type 1 diabetes. The case children (N = 343) were positive for at least one islet autoantibody, and the control children (N = 343) matched by age, gender and class II HLA genotype were negative for islet autoantibodies at the time of data collection. Extended family history of type 1 diabetes was obtained by using a structured questionnaire.

Results: Among children who were autoantibody positive and progressed to type 1 diabetes 62.2% (28/45) had at least one relative with type 1 diabetes. Interestingly, 57.8% of these children (26/45) had such a relative outside the nuclear family compared to 30.7% of children with no autoantibodies (P = .001), 35.2% of those with only classical islet cell antibodies (P = .006), and 35.2% of non‐progressors with biochemical autoantibodies (P = 0.011). A positive history of type 1 diabetes in the paternal extended family was more common in children with multiple biochemical autoantibodies compared to those with only one biochemical autoantibody (P = .010). No association between the specificity of the first appearing autoantibody and family history of the disease was found.

Conclusions: Type 1 diabetes in relatives outside the nuclear family is a significant risk factor for islet autoimmunity and progression to clinical disease in HLA susceptible children.

see all

Series: Pediatric diabetes
ISSN: 1399-543X
ISSN-E: 1399-5448
ISSN-L: 1399-543X
Volume: 21
Issue: 8
Pages: 1447 - 1456
DOI: 10.1111/pedi.13122
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3123 Gynaecology and paediatrics
Funding: Academy of Finland, Grant/Award Number: 292538; Centre of Excellence in Molecular Systems Immunology and Physiology Research, Grant/Award Number: 250114; Diabetes Research Foundation, Finland; European Commission, Grant/Award Number: BMH4‐CT98‐3314; Juvenile Diabetes Research Foundation International (JDRF), Grant/Award Numbers: 1‐SRA‐2016‐342‐M‐R, 1‐SRA‐2019‐732‐M‐B; Novo Nordisk Fonden; Pediatric Research Foundation, Finland; Sigrid Juselius Foundation, Finland; Special Research Funds for University Hospitals in Finland; The Alma and K.A. Snellman Foundation, Finland; The Finnish Medical Foundation.
Copyright information: © 2020 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.