title: Family history of diabetes and distribution of class II HLA genotypes in children with newly diagnosed type 1 diabetes: effect on diabetic ketoacidosis.
abstract: OBJECTIVE
  Our purpose was to assess whether family history of diabetes or the HLA-DR-DQ genotype of the index case was associated with the frequency of diabetic ketoacidosis (DKA) at diagnosis of childhood type 1 diabetes.
  
  
  METHODS
  The study cohort comprised 1518 children aged <15 years and diagnosed with type 1 diabetes in Finland in 2002-2005. Family history of type 1 and type 2 diabetes among first-degree relatives (FDRs) and grandparents was assessed at diagnosis. HLA-DR-DQ genotypes were analysed using time-resolved fluorometry.
  
  
  RESULTS
  In total, 12.6 and 1.7% of children had at least one FDR affected with type 1 or type 2 diabetes, respectively, and 6.6 and 34.8% had at least one grandparent with type 1 or type 2 diabetes. DKA (pH <7.30) occurred less frequently in children having a type 1 diabetes affected FDR (7.4 vs 20.5%, P<0.001). Type 2 diabetes among the parents or grandparents had no such effect. Lower risk HLA genotypes were observed to predispose to DKA (P<0.024). In a logistic regression analysis, the risk of DKA was independently associated with the absence of a family member affected by type 1 diabetes, the presence of a low-risk HLA genotype and older age at diagnosis (odds ratio 3.23, 1.45 and 1.07 respectively).
  
  
  CONCLUSIONS
  The presence of type 1 diabetes in an FDR is associated with an decreased risk of DKA at diagnosis. The rate of DKA seems to be higher in children with lower HLA-conferred risk for type 1 diabetes.
authors: Department of Paediatrics, Institute of Clinical Medicine, University of Oulu, PO Box 5000, 90014 Oulu, Finland. anne.hekkala@oulu.fi
authors: Anne
authors: A
authors: Hekkala
authors: Jorma
authors: J
authors: Ilonen
authors: Mikael
authors: M
authors: Knip
authors: Riitta
authors: R
authors: Veijola
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016883:Diabetic Ketoacidosis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens