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

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.

• Authors: A Carlsson, I Kockum, B Lindblad, L Engleson, A Nilsson, G Forsander, A-K Karlsson, A Kernell, J Ludvigsson, C Marcus, I Zachrisson, S-A Ivarsson, A Lernmark, Swedish Better Diabetes Diagnosis Study Group
• Journal: International journal of obesity (2005) (Int J Obes (Lond)) Vol. 36 Issue 5 Pg. 718-24 (May 2012) ISSN: 1476-5497 [Electronic] England
• PMID: 21712811 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DQ Antigens

Topics

• Adolescent
• Age Factors
• Body Mass Index
• Child
• Child, Preschool
• Cohort Studies
• Diabetes Mellitus, Type 1 (diagnosis, epidemiology, genetics)
• Female
• Genetic Predisposition to Disease
• HLA-DQ Antigens (genetics)
• Haplotypes
• Humans
• Male
• Obesity (epidemiology, genetics)
• Odds Ratio
• Prospective Studies
• Sweden (epidemiology)