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

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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; Kockum, I; Lindblad, Bengt; Engleson, Lisa; Nilsson, A; Forsander, G; Karlsson, A-K; Kernell, A; Ludvigsson, J; Marcus, C; Zachrisson, I; Ivarsson, Sten; Lernmark, Åke.

In: International Journal of Obesity, Vol. 36, 2012, p. 718-724.

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Carlsson, A, Kockum, I, Lindblad, B, Engleson, L, Nilsson, A, Forsander, G, Karlsson, A-K, Kernell, A, Ludvigsson, J, Marcus, C, Zachrisson, I, Ivarsson, S & Lernmark, Å 2012, 'Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden.', International Journal of Obesity, vol. 36, pp. 718-724. https://doi.org/10.1038/ijo.2011.122

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Carlsson, Annelie ; Kockum, I ; Lindblad, Bengt ; Engleson, Lisa ; Nilsson, A ; Forsander, G ; Karlsson, A-K ; Kernell, A ; Ludvigsson, J ; Marcus, C ; Zachrisson, I ; Ivarsson, Sten ; Lernmark, Åke. / Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden. In: International Journal of Obesity. 2012 ; Vol. 36. pp. 718-724.

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TY - JOUR

T1 - Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden.

AU - Carlsson, Annelie

AU - Kockum, I

AU - Lindblad, Bengt

AU - Engleson, Lisa

AU - Nilsson, A

AU - Forsander, G

AU - Karlsson, A-K

AU - Kernell, A

AU - Ludvigsson, J

AU - Marcus, C

AU - Zachrisson, I

AU - Ivarsson, Sten

AU - Lernmark, Åke

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1038/ijo.2011.122

DO - 10.1038/ijo.2011.122

M3 - Article

VL - 36

SP - 718

EP - 724

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 1476-5497

ER -