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

Salla Kuusela, Päivi Keskinen, Tytti Pokka, Mikael Knip, Jorma Ilonen, Paula Vähäsalo, Riitta Veijola

Research output: Contribution to journalArticleScientificpeer-review


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.

Original languageEnglish
Pages (from-to)1447-1456
Number of pages10
Issue number8
Publication statusPublished - Dec 2020
Publication typeA1 Journal article-refereed


  • children
  • family history
  • genetic risk
  • HLA
  • islet autoimmunity
  • type 1 diabetes

Publication forum classification

  • Publication forum level 2

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism


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