title: Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden.
abstract: OBJECTIVE
  Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes human leukocyte antigen DQ (HLA-DQ) risk genotypes may be associated with increased body mass index (BMI).
  
  
  METHODS
  The type 1 diabetes high-risk HLA-DQ A1*05:01-B1*02:01/A1*03:01-B1*03:02 genotype along with lower risk DQ genotypes were determined at the time of clinical onset by PCR and hybridization with allele-specific probes. BMI was determined after diabetes was stabilized.
  
  
  METHODS
  A total of 2403 incident type 1 diabetes children below 18 years of age were ascertained in the Swedish national Better Diabetes Diagnosis (BDD) study between May 2005 to September 2009. All children classified with type 1 diabetes, including positivity for at least one islet autoantibody, were investigated.
  
  
  RESULTS
  Overall, type 1 diabetes HLA-DQ risk was negatively associated with BMI (P<0.0008). The proportion of the highest risk A1*05:01-B1*02:01/A1*03:01-B1)03:02 genotype decreased with increasing BMI (P<0.0004). However, lower risk type 1 diabetes DQ genotypes were associated with an increased proportion of patients who were overweight or obese (P<0.0001). Indeed, the proportion of patients with the low-risk A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype increased with increasing BMI (P<0.003). The magnitude of association on the multiplicative scale between the A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype and increased BMI was significant (P<0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% confidence interval 1.21-2.61; P<0.006). The increased proportion of overweight type 1 diabetes children with the A1*05:01-B1*02:01 haplotype was most pronounced in children diagnosed between 5 and 9 years of age.
  
  
  CONCLUSIONS
  Susceptibility for childhood type 1 diabetes was unexpectedly found to be associated with the A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype and an increased BMI. These results support the hypothesis that overweight may contribute to the risk of type 1 diabetes in children positive for HLA-DQ A1*05:01-B1*02:01.
authors.affiliation: Department of Pediatrics, Skåne University Hospital SUS, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: B
authors.initials: B
authors.lastname: Lindblad
authors.forename: L
authors.initials: L
authors.lastname: Engleson
authors.forename: A
authors.initials: A
authors.lastname: Nilsson
authors.forename: G
authors.initials: G
authors.lastname: Forsander
authors.forename: A-K
authors.initials: AK
authors.lastname: Karlsson
authors.forename: A
authors.initials: A
authors.lastname: Kernell
authors.forename: J
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: C
authors.initials: C
authors.lastname: Marcus
authors.forename: I
authors.initials: I
authors.lastname: Zachrisson
authors.forename: S-A
authors.initials: SA
authors.lastname: Ivarsson
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D011446:Prospective Studies; D013548:Sweden / Q000453:epidemiology
chemical_list: D006683:HLA-DQ Antigens