Prevalence of asthmatic symptoms in Lebanese patients with type 1 diabetes and their unaffected siblings compared to age-matched controls

Abstract

Patients with type 1 diabetes (a TH1 disease) have been reported to be at a lower risk of developing asthma (a TH2 disease). Both diseases are affected by environmental and genetic factors. Our objective is to examine this relationship in Lebanon, a Middle-Eastern country, where no previous similar studies are available. This is a cross-sectional observational study conducted at the Chronic Care Center, a referral medical center for type 1 diabetics. Patients with type 1 diabetes aged 6–39 years old, their unaffected siblings and age-matched control completed the International Primary Care Airways Group asthma screening questionnaire. The prevalence of asthma symptoms was compared among the three groups and separately within a subgroup of diabetics in relation to their carrier state of previously collected genetic data. Among 305 diabetics, 776 siblings and 187 controls, diabetics were at lower risk of having any asthma symptoms than controls; OR 0.48 (95% CI 0.32–0.72, p < 0.001) and siblings were at lower risk than diabetics and controls; OR 0.64 (95% CI 0.45–0.91, p = 0.01) and 0.28 (95% CI 0.19–0.42, p < 0.001), respectively. Among 66 diabetics, carriers of the HLA-DQB1*0201 allele were at lower risk of having any asthma symptoms than non-carriers (25.5 vs. 53.3%, p = 0.04). Only a statistically non-significant trend of higher risk was observed in carriers of HLA-DQB1*0301 and G allele at the 49 (A/G) nucleotide of CTLA-4 gene. The TH1–TH2 paradigm might partially explain these findings, since siblings were the least to report asthma symptoms. Future research is needed with diagnostic tests for asthma and extensive genetic testing.

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Fig. 1

Abbreviations

Th1:

T helper type 1

Th2:

T helper type 1

T1DM:

Type 1 diabetes mellitus

IPAG:

International Primary Care Airways Group

CCC:

Chronic Care Center

References

  1. 1.

    Kero J, Gissler M, Hemminki E, Isolauri E (2001) Could TH1and TH2 diseases coexist? Evaluation of asthma incidence in children with celiac disease, type 1 diabetes, or rheumatois arthritis: a register study. J Allergy Clin Immunol 108:781–783

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Chitnis T, Salama AD, Grusby MJ, Sayegh MH, Khoury SJ (2004) Defining Th1 and Th2 immune responses in a reciprocal cytokine environment in vivo. J Immunol 172:4260–4265

    CAS  PubMed  Google Scholar 

  3. 3.

    Cardwell C, Shields M, Carson D, Patterson C (2003) A meta-analysis of the association between childhood type 1 diabetes and atopic disease. Diabetes Care 26:2568–2574

    Article  PubMed  Google Scholar 

  4. 4.

    Zalloua P, Abchee A, Shbaklo H, Zreik T, Terwedow H, Halaby G, Azar S (2004) Patients with early onset of type 1 diabetes have significantly higher GG genotype at position 49 of the CTLA4 gene. Hum Immunol 65(7):719–724

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Zalloua P, Shbaklo H, Halaby G, Terwedow H, Xu X, Azar S (2002) Type-2 diabetes family history delays the onset of type-1 diabetes. J Clin Endocrinol Metab 87(7):3192–3196

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Gao J, Lin Y, Qiu C, Liu Y, Ma Y, Liu Y (2003) Association between HLA-DQA1, -DQB1 gene polymorphisms and susceptibility to asthma in northern Chinese subjects. Chin Med J (Engl) 116(7):1078–1082

    CAS  Google Scholar 

  7. 7.

    Mochizuchi M, Mochizuki M, Amemiya S, Kobayashi Ki, Kobayashi Ko, Shimura Y, Ishihara T, Nakagomi Y, Onigata K, Tamai S, Kasuga A, Nanazawa S (2003) Association of CTLA4 gene 49 A/G Polymorphism with Type 1 Diabetes and Autoimmune Thyroid Disease in Japanese Children. Diabetes Care 26:843–847

    Article  Google Scholar 

  8. 8.

    Waked M, Salameh P (2006) Asthma, allergic rhinitis and eczema in 13–14-year-old schoolchildren across Lebanon. J Med Liban 54(4):181–190

    PubMed  Google Scholar 

  9. 9.

    Waked M, Salameh P (2008) Asthma, allergic rhinitis and eczema in 5–12-year-old schoolchildren across Lebanon. Public health 122(9):965–973

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Eder W, Ege M, Mutius Von E (2006) The asthma epidemic. N Engl J Med 355:2226–2235

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    International Primary Care Airways Group (IPAG). Chronic airway diseases: a guide for primary care physicians. http://www.Ipagguide.org/IPAG.copyrightdraft.pdf

  12. 12.

    Tanriverdi F, Silveira LF, MacColl GS, Bouloux PM (2003) The hypothalamic-pituitary-gonadal axis: immune function and autoimmunity. J Endocrinol 176:293–304

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Tzeng S, Hsu S, Fu L, Chi C (2007) Prevalence of atopy in children with type 1 diabetes mellitus in central Taiwan. J Microbiol Immunol Infect 40:74–78

    PubMed  Google Scholar 

  14. 14.

    Berger A (2000) Th1 and Th2 responses: what are they? BMJ 321:424

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Singh VK, Mehrotra S, Agarwal SS (1999) The paradigm of Th1 and Th2 cytokines: its relevance to autoimmunity and allergy. Immunol Res 20:147–161

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Rachmiel M, Bloch O, Bistritzer T, Weintrob N, Ofan R, Koren–Morag N, Rapoport M (2006) TH1/TH2 cytokine balance in patients with both type diabetes and asthma. Cytokine 34:170–176

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Azar S, Tamim H, Beyhum H, Habbal M, Almawi W (1999) Type T (Insulin Dependent) diabetes is a Th1- and Th2- mediated autoimmune disease. Clin Diagn Lab Immunol 6(3):306–310

    CAS  PubMed  Google Scholar 

  18. 18.

    Rabin R, Levinson A (2008) The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature. Clin Exp Immunol 153(1):19–30

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Huang S, Hitchcock J (2002) Influence of the TH1/TH2 paradigm: the prevalence of asthma and allergic diseases in patients with type 1 diabetes in the United States. Pediatr Asthma Allerg Immunol 15(4):195–199

    Article  Google Scholar 

  20. 20.

    Douek I, Leech N, Gillmor H, Bingley P, Gale E (1999) Children with type-1 diabetes and their unaffected siblings have fewer symptoms of asthma. Lancet 353:1850

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Parapanissiou E, Papastavrou T, Deligiannidis A, Adam K, Kanakoudi F, Daniilidis M, Polymenidis Z (2005) HLA antigens in Greek children with allergic bronchial asthma. Tissue Antigens 65(5):481–484

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Santos J, Pérez-Bravo F, Carrasco E, Calvillán M, Albala C (2001) Association between HLA-DQB1 alleles and type 1 diabetes in a case-parents study conducted in Santiago, Chile. Am J Epidemiol 153:794–798

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Horne C, Quintana PJ, Keown PA, Dimich-Ward H, Chan-Yeung M (2000) Distribution of DRB1 and DQB1 HLA class II alleles in occupational asthma due to western red cedar. Eur Respir J 15(5):911–914

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Huang S (1999) Asthma and diabetes. Lancet 353:515–516

    Article  Google Scholar 

  25. 25.

    Munthe-Kaas MC, Carlsen KH, Helms PJ, Gerritsen J, Whyte M, Feijen M, Skinningsrud B, Main M, Kwong GN, Lie BA, Lødrup Carlsen KC, Undlien DE (2004) CTLA-4 polymorphisms in allergy and asthma and the TH1/TH2 paradigm. J Allergy Clin Immunol 114(2):280–287

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Ober C, Hoffjan S (2006) Asthma genetics 2006: the long and winding road to gene discovery. Genes Immunity 7:95–100

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Jasek M, Łuszczek W, Obojski A, Winiarska B, Hałubek K, Nowak I, Mańczak M, Wiśniewski A, Pawlik A, Jonkisz A, Lebioda A, Majorczyk E, Dobosz T, Kuśnierczyk P (2006) Distribution of CTLA-4 polymorphysmis in allergic asthma. Int Arch Allergy Immunol 141:223–229

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Lee S, Lee Y, Shin C, Shim J, Kang K, Yoo S, In K (2002) Association of asthma severity and bronchial hyperresponsiveness with a polymorphism in the cytotoxic T-lymphocyte antigen-4 gene. Chest 122:171–176

    CAS  Article  PubMed  Google Scholar 

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Acknowledgments

The valuable assistance of Mrs. Claude Sadek, Colette Bitar and Pascal Nawfal in the collection of questionnaires at the Chronic Care Center is highly appreciated.

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Correspondence to Sami T. Azar.

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N. Taleb and P. Bou Khalil have contributed equally to this work.

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Taleb, N., Bou Khalil, P., Zantout, M.S. et al. Prevalence of asthmatic symptoms in Lebanese patients with type 1 diabetes and their unaffected siblings compared to age-matched controls. Acta Diabetol 47, 13–18 (2010). https://doi.org/10.1007/s00592-009-0108-5

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Keywords

  • Type 1 diabetes
  • Asthma
  • TH1/TH2 paradigm
  • HLA-DQB1
  • 49 (A/G) CTLA4