Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden
A Carlsson, I Kockum, B Lindblad, L Engleson… - International journal of …, 2012 - nature.com
A Carlsson, I Kockum, B Lindblad, L Engleson, A Nilsson, G Forsander, AK Karlsson…
International journal of obesity, 2012•nature.comObjective: 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 …
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 …
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< 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.
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