Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden
2012 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, no 5, 718-724 p.Article in journal (Refereed) Published
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). less thanbrgreater than less thanbrgreater thanDesign: 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. less thanbrgreater than less thanbrgreater thanSubjects: 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. less thanbrgreater than less thanbrgreater thanResults: Overall, type 1 diabetes HLA-DQ risk was negatively associated with BMI (Pandlt;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 (Pandlt;0.0004). However, lower risk type 1 diabetes DQ genotypes were associated with an increased proportion of patients who were overweight or obese (Pandlt;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 (Pandlt;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 (Pandlt;0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% confidence interval 1.21-2.61; Pandlt;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. less thanbrgreater than less thanbrgreater thanConclusions: 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.
Place, publisher, year, edition, pages
Nature Publishing Group , 2012. Vol. 36, no 5, 718-724 p.
islet autoantibodies, body mass index, GAD65 autoantibodies, IA-2 autoantibodies, insulin autoantibodies, HLA genotype
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-77863DOI: 10.1038/ijo.2011.122ISI: 000303771000012OAI: oai:DiVA.org:liu-77863DiVA: diva2:529708
Funding Agencies|Swedish Child Diabetes Foundation||National Institutes of Health|DK63861DK26190|Swedish Research Council||Swedish Diabetes Association||Knut & Alice Wallenberg Foundation||Lion Club International District 101-S||Skane County Council for Research and Development||2012-05-312012-05-312012-05-31