Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children
- Anna Parkkola, MD1,
- Taina Härkönen, PHD1,
- Samppa J. Ryhänen, MD, PHD1,
- Jorma Ilonen, MD, PHD2,3,
- Mikael Knip, MD, PHD1,4,5⇓ and
- the Finnish Pediatric Diabetes Register*
- 1Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
- 2Immunogenetics Laboratory, University of Turku, Turku, Finland
- 3Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland
- 4Folkhälsan Research Center, Helsinki, Finland
- 5Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- Corresponding author: Mikael Knip, .
OBJECTIVE To determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes and to characterize the effects of this positive family history on clinical markers, signs of β-cell autoimmunity, and HLA genotype in the index case.
RESEARCH DESIGN AND METHODS Children (n = 1,488) with type 1 diabetes diagnosed under 15 years of age were included in a cross-sectional study from the Finnish Pediatric Diabetes Register. Data on family history of diabetes and metabolic decompensation at diagnosis were collected using a questionnaire. Antibodies to β-cell autoantigens (islet cell antibodies, insulin auto antibodies, glutamic acid decarboxylase antibodies, and antibodies to the islet antigen 2 molecule) and HLA genotypes were analyzed.
RESULTS A total of 12.2% of the subjects had a first-degree relative with type 1 diabetes (father 6.2%, mother 3.2%, and sibling 4.8%) and 11.9% had an affected second-degree relative. Children without affected relatives had lower pH (P < 0.001), higher plasma glucose (P < 0.001) and β-hydroxybutyrate concentrations (P < 0.001), a higher rate of impaired consciousness (P = 0.02), and greater weight loss (P < 0.001). There were no differences in signs of β-cell autoimmunity. The familial cases carried the HLA DR4-DQ8 haplotype more frequently than sporadic cases (74.0 vs. 67.0%, P = 0.02).
CONCLUSIONS When the extended family history of type 1 diabetes is considered, the proportion of sporadic diabetes cases may be reduced to <80%. A positive family history for type 1 diabetes associates with a less severe metabolic decompensation at diagnosis even when only second-degree relatives are affected. Autoantibody profiles are similar in familial and sporadic type 1 diabetes, suggesting similar pathogenetic mechanisms.
↵*A complete list of the investigators of the Finnish Pediatric Diabetes Register can be found in the APPENDIX.
- Received March 6, 2012.
- Accepted July 26, 2012.
- © 2012 by the American Diabetes Association.
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