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

OBJECTIVE: Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes HLA-DQ risk genotypes may be associated with an 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. Body mass index 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) studybetween 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 body mass index (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 body mass index was significant (p<0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% CI 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.