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Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden.

Carlsson, Annelie LU ; Kockum, I; Lindblad, Bengt LU ; Engleson, Lisa LU ; Nilsson, A; Forsander, G; Karlsson, A-K; Kernell, A; Ludvigsson, J and Marcus, C, et al. (2012) In International Journal of Obesity 36. p.718-724
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).Design: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.Subjects: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... (More)
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).Design: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.Subjects: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.International Journal of Obesity advance online publication, 28 June 2011; doi:10.1038/ijo.2011.122. (Less)
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International Journal of Obesity
volume
36
pages
718 - 724
publisher
Nature Publishing Group
external identifiers
  • wos:000303771000012
  • pmid:21712811
  • scopus:84860783172
ISSN
1476-5497
DOI
10.1038/ijo.2011.122
language
English
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yes
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7a7571f2-01ec-4876-a91f-9a74a517e2c6 (old id 2007661)
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http://www.ncbi.nlm.nih.gov/pubmed/21712811?dopt=Abstract
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2011-07-06 11:29:31
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2017-11-12 04:06:37
@article{7a7571f2-01ec-4876-a91f-9a74a517e2c6,
  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).Design: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.Subjects: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&lt;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&lt;0.0004). However, lower risk type 1 diabetes DQ genotypes were associated with an increased proportion of patients who were overweight or obese (P&lt;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&lt;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&lt;0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% confidence interval 1.21-2.61; P&lt;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.International Journal of Obesity advance online publication, 28 June 2011; doi:10.1038/ijo.2011.122.},
  author       = {Carlsson, Annelie and Kockum, I and Lindblad, Bengt and Engleson, Lisa and Nilsson, A and Forsander, G and Karlsson, A-K and Kernell, A and Ludvigsson, J and Marcus, C and Zachrisson, I and Ivarsson, Sten and Lernmark, Åke},
  issn         = {1476-5497},
  language     = {eng},
  pages        = {718--724},
  publisher    = {Nature Publishing Group},
  series       = {International Journal of Obesity},
  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.},
  url          = {http://dx.doi.org/10.1038/ijo.2011.122},
  volume       = {36},
  year         = {2012},
}