title: Extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children.
abstract: 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.
  
  
  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 autoantibodies, GAD 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.
authors.affiliation: Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Parkkola
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.forename: Samppa J
authors.initials: SJ
authors.lastname: Ryhänen
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D005190:Family; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D006683:HLA-DQ Antigens; D020155:3-Hydroxybutyric Acid