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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.

Author:
  • Annelie Carlsson
  • I Kockum
  • Bengt Lindblad
  • Lisa Engleson
  • A Nilsson
  • G Forsander
  • A-K Karlsson
  • A Kernell
  • J Ludvigsson
  • C Marcus
  • I Zachrisson
  • Sten Ivarsson
  • Åke Lernmark
Publishing year: 2012
Language: English
Pages: 718-724
Publication/Series: International Journal of Obesity
Volume: 36
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Nutrition and Dietetics

Other

Published
  • Vascular Diseases - Clinical Research
  • Diabetes and Celiac Unit
  • Paediatric Endocrinology
  • ISSN: 1476-5497
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00