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  • Original Article
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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

International Journal of Obesity volume 36, pages 718–724 (2012)Cite this article

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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Acknowledgements

We thank Ali Shalouie, Barbro Gustavsson, Ida Hansson, Rasmus Håkansson, Britt Buveris and Qefsere Bramini for expert technical assistance. We also thank the Epidemiologic Investigation of Multiple Sclerosis study group for kindly sharing their data on BMI and HLA in the general Swedish population. This study was supported in part by the Swedish Child Diabetes Foundation, the National Institutes of Health (DK63861, DK26190), the Swedish Research Council, the Swedish Diabetes Association Research Fund, Knut & Alice Wallenberg Foundation, Lion Club International District 101-S and the Skåne County Council for Research and Development.

Author information

Author notes

  1. 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 and Å Lernmark: A Carlsson and I Kockum: These authors contributed equally to the study.

  2. Members are listed in the Appendix.

  3. A Kernell: Deceased May 2009.

Authors and Affiliations

  1. Department of Pediatrics, Sk,

    A Carlsson & L Engleson

  2. å,

    A Carlsson & L Engleson

  3. ne University Hospital SUS, Lund, Sweden

    A Carlsson & L Engleson

  4. Department of Clinical Neurosciences, Karolinska Institute, Stockholm, Sweden

    I Kockum

  5. Department of Pediatrics, The Queen Silvia Children's Hospital, G, ö, teborg, Sweden

    B Lindblad, G Forsander & A-K Karlsson

  6. Department of Clinical Sciences/CRC, Lund University, Sk,

    A Nilsson & Å Lernmark

  7. å,

    A Nilsson & Å Lernmark

  8. ne University Hospital SUS, Malm, ö, Sweden

    A Nilsson & Å Lernmark

  9. Sachs’ Children Hospital, S,

    A Kernell

  10. ö,

    A Kernell

  11. dersjukhuset, Stockholm, Sweden

    A Kernell

  12. Department of Clincial and Experimental Medicine, Divison of Pediatrics and Diabetes Research Center, Link,

    J Ludvigsson

  13. ö,

    J Ludvigsson

  14. ping University Hospital, Link, ö, ping, Sweden

    J Ludvigsson

  15. Department of Clinical Science, Division of Pediatrics, Intervention and Technology, Karolinska Institute, Stockholm, Sweden

    C Marcus

  16. Department of Woman and Child Health, Pediatric Endocrinology Unit, Karolinska Institute, Stockholm, Sweden

    I Zachrisson

  17. Department of Pediatrics, Lund University, Sk,

    S-A Ivarsson

  18. å,

    S-A Ivarsson

  19. ne University Hospital SUS, Malm, ö, Sweden

    S-A Ivarsson

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  1. A Carlsson
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for the Swedish Better Diabetes Diagnosis Study Group

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Correspondence to Å Lernmark.

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Additional information

Supplementary Information accompanies the paper on International Journal of Obesity website

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Appendix

Appendix

Members of the BDD Study Group include Bengt-Olof Samuelsson (Borås), Kalle Snellman (Eskilstuna), Anna Olivecrona (Falun), Åke Stenberg (Gällivare), Lars Skogsberg (Gävle), Nils Östen Nilsson (Halmstad), Jan Neiderud (Helsingborg), Torun Torbjörnsdotter (Huddinge), Thomas Hägg (Hudiksvall), Kristina Hemmingsson (Härnösand), Göran Lundström (Kalmar), Magnus Ljungcrantz (Karlskrona), Maria Forsberg (Karlstad), Karin Larsson (Kristianstad), Christer Gundewall (Kungsbacka), Karin Åkesson (Jönköping), Rebecka Enander (Lidköping), Ulf Samuelsson (Linköping), Helena E Larsson (Malmö), Agneta Brännström (Luleå), Maria Nordwall (Norrköping), Lennart Hellenberg (Nyköping), Elena Lundberg (Skellefteå), Henrik Tollig (Skövde), Britta Björsell (Sollefteå), Eva Örtqvist (Stockholm/KS), Björn Stjernstedt (Sundsvall), Nils Wramner (Trollhättan), Ragnar Hanås (Uddevalla), Ingemar Swenne (Uppsala), Margareta Blomgren (Visby), Anders Thåström (Västervik), CG Arvidsson (Västerås), Stig Edvardsson (Växjö), Björn Jönsson (Ystad), Torsten Gadd (Ängelholm), Jan Åman (Örebro), Rein Florell (Örnsköldsvik) and Anna-Lena Fureman (Östersund).

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Carlsson, A., Kockum, I., Lindblad, B. et al. Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden. Int J Obes 36, 718–724 (2012). https://doi.org/10.1038/ijo.2011.122

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