Journal of Molecular Medicine

, Volume 74, Issue 2, pp 105–109 | Cite as

Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children

  • F. Pérez-Bravo
  • E. Carrasco
  • M. D. Gutierrez-López
  • M. T. Martínez
  • G. López
  • M. García de los Rios
Original Article

Abstract

This study was designed to examine the hypothesis that some environmental factors increase the risk for insulin-dependent diabetes mellitus. Data on dietary history was collected from 80 diabetic children from the Santiago de Chile Registry and from 85 nondiabetic control subjects who were comparable in terms of age, sex, and ethnic characteristics. Early exposure was defined as the ingestion of food sources other than maternal milk before 3 months of age. To define genetic susceptibility to insulin-dependent diabetes mellitus each subject was typed in terms of HLA DQA1 and DQB1, and the possible conformation of susceptible heterodimers was considered as a risk marker. Fewer children were exclusively breast fed in the diabetic group than in the control group (21.55±15.05 vs. 33.95±20.40 weeks, P<0.01). In addition, exposure to cow's milk and solid foods occurred earlier in the diabetic group than in the control group (15.90±10.95 vs. 21.15 13.65 and 16.85±10.25 vs. 21.20±12.35 weeks, P<0.05). Our data show that a short duration of breast-feeding and early exposure to cow's milk and solid foods may be important factors in the development of insulin-dependent diabetes mellitus. The high relative risk observed in individuals genetically predisposed indicates an interaction effect between genetic and environmental components.

Key words

Insulin-dependent diabetes mellitus Cow's milk exposure Genetic predisposition Solid foods Infant diet Breast-feeding 

Abbreviations

IDDM

Insulin-dependent diabetes mellitus

RR

Relative risk

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References

  1. 1.
    Bach JF (1994) Insulin-dependent diabetes mellitus as an autoimmune disease. Endocrine Rev 15:516–542Google Scholar
  2. 2.
    Todd JA (1990) Genetic control of autoimmunity in type I diabetes. Immunol Today 11:122–129Google Scholar
  3. 3.
    Nepon JT (1990) A unified hypothesis for the complex genetics of HLA associations with IDDM. Diabetes 39:1153–1157Google Scholar
  4. 4.
    Sheeny MJ (1992) HLA and insulin-dependent diabetes. A protective perspective. Diabetes 41:123–129PubMedGoogle Scholar
  5. 5.
    Thorsby E, Ronningen KS (1993) Particular HLA-DQ molecules play a dominant role in determining susceptibility or resistance to type I (insulin-dependent) diabetes mellitus. Diabetologia 36:371–377Google Scholar
  6. 6.
    Yoon J-W (1991) Role of viruses in the pathogenesis of IDDM. Ann Med 23:437–445Google Scholar
  7. 7.
    Szopa TM, Titchener PA, Portwood ND, Taylor KW (1993) Diabetes mellitus due to viruses — some recents developments. Diabetologia 36:687–695Google Scholar
  8. 8.
    Fohlman J, Friman G (1993) Is juvenile diabetes a viral disease? Ann Med 25:569–574Google Scholar
  9. 9.
    Kivik KO, Green A, Svendsen A, Mortensen K (1992) Breast-feeding and the development of type I diabetes mellitus. Diabetic Med 9:233–235Google Scholar
  10. 10.
    Borch-Johnsen K, Joner G, Mandroup-Poulsen T, Christy M, Zachau-Christiansen B, Kastrup K, Nepon J (1984) Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. Lancet II:1083–1086Google Scholar
  11. 11.
    Kostraba JN, Cruickshanks KJ, Lawler-Heavner J, Jobin LF, Rewers MJ, Gay EC, Chase HP, Klingesmith G, Hamman RF (1993) Early exposure to cow's milk and solid foods in infancy, genetic predisposition and risk of IDDM. Diabetes 42:288–295Google Scholar
  12. 12.
    Kostraba JN, Dorman JS, LaPorte RE, Scott FW, Steekiste AR, Gloninger M, Drash A (1992) Early infant diet and risk of insulin-dependent diabetes mellitus in blacks and whites: a matched case control study. Diabetes Care 15:626–631Google Scholar
  13. 13.
    Virtanen SM, Rasanen L, Aro A, Lindrom J, Sippola H, Louramaa R, Toivanen L, Tuomilehto J, Akerblom HK (1991) Infant feeding in Finish children<7 yr of age with newly diagnosed IDDM. Diabetes Care 14:415–417Google Scholar
  14. 14.
    Martin JM, Trink B, Daneman D, Dosch HM, Robinson B (1991) Milk proteins in the etiology of insulin-dependent diabetes mellitus (IDDM). Ann Med 23:447–452Google Scholar
  15. 15.
    Virtanen SM, Saukkonen T, Savilahti E, Ylonen K, Rasanen L, Aro A, Knip M, Tuomilehto J, Akerblom HK (1994) Diet, cow's milk protein antibodies and the risk of IDDM in Finnish children. Diabetologia 37:381–387Google Scholar
  16. 16.
    Karjalainen J, Martin JM, Knip M, Ylonen J, Robinson B, Savilahti E, Akerblom HK, Dosch HM (1992) A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. N Engl J Med 327:302–307Google Scholar
  17. 17.
    Karjalainen J, Saukkonen T, Savilahti E, Dosch HM (1992) Disease-associated anti-bovine serum albumin antibodies in type I (insulin-dependent) diabetes mellitus are detected by particle concentration fluoroimmunoassay, and not by enzyme linked immunoassay. Diabetologia 35:985–990Google Scholar
  18. 18.
    Dahlquist G, Savilahti E, Landin-Olsson M (1992) An increased level of antibodies to β-lactoglobulin in a risk determinant for early-onset type I (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow's milk. Diabetologia 35:980–984Google Scholar
  19. 19.
    Saukkonen T, Savilahti E, Vaarala O, Virtala ET, Tuomilehto J, Akerblom HK (1994) Children with newly diagnosed IDDM have increased levels of antibodies to bovine serum albumin but not to Ovalbumin. Diabetes Care 17:970–976Google Scholar
  20. 20.
    Krokowski M, Caillat-Zucman S, Timsit J, Larger E, PehuetFigoni M, Bach JF, Boitard C (1995) Anti-bovine serum albumin antibodies: genetic heterogeneity and clinical relevance in adult-onset IDDM. Diabetes Care 18:170–173Google Scholar
  21. 21.
    Carrasco E, López G, Garcia de los Rios M, Vargas N (1992) Incidencia de diabetes mellitus insulinodependiente en menores de 15 años. Període 90–91. Santiago de Chile. Rev Soc Argent de Diabetes 26 [Suppl]:14A (abstract)Google Scholar
  22. 22.
    Valenzuela C (1988) Marco de referencia sociogenético para los estudios de salud pública en Chile. Rev Chil Pedriatr 55:123–127Google Scholar
  23. 23.
    Sambrook J, Fritsh EF, Maniatis TM (1989) Molecular cloning. A laboratory manual, 2nd edn. Cold Springs Harbor Laboratory, Cold Springs HarborGoogle Scholar
  24. 24.
    Gutierrez-López MD, Bertera S, Chantres MT, Vavassori C, Dorman JS, Trucco M, Serrano-Rios M (1992) Susceptibility to type I (insulin-dependent) diabetes mellitus in Spanish patients correlates quantitatively with expression of HLA-DQA Arg 52 and HLA-DQB non Asp 57 alleles. Diabetologia 35:583–588Google Scholar
  25. 25.
    Pérez-Bravo F, Gutierrez-López MD, Calvillán M, Dorman JS, Trucco M, Serrano-Rios M (1994) Quantitative effect of HLA DR and BDQ heterodimers in type I diabetes mellitus in two latinamerican populations: Chile and Peru. Eur J Clin Invest 24 [Suppl]:A7 (abstract)Google Scholar
  26. 26.
    Perez-Bravo F, Serrano-Rios M, Gutierrez-López MD, Calvillán M, García de los Rios M, Kocova M, Dorman JS, Trucco M (1995) Genetic analysis of HLA DRB1, DQA1 and DQB1 alleles and susceptibility to IDDM in Chilean subjects. Diabetologia 38:378–379 (letter)Google Scholar
  27. 27.
    Khalil I, Deschamps I, Lepage V, Al-Daccak R, Degos L, Hors J (1992) Dose effect of cis and trans encoded HLA-DQ alpha/beta heterodimers in IDDM susceptibility. Diabetes 41:378–384Google Scholar
  28. 28.
    Mella I, García de los Rios M, Parker M, Covarrubias A (1981) Prevalencia de la diabetes en el gran Santiago, Chile. Rev Med Chile 109:869–872Google Scholar
  29. 29.
    Gunczlen P, Lanes R, Layrisse Z, Esparza B, Salas R, Hernandez L, Arnaiz-Villena A (1993) Epidemiology and immunogenetics in recently diagnosed Venezuelan children with insulin-dependent diabetes mellitus. J Pediatr Endocrinol 6:165–171Google Scholar
  30. 30.
    Hyoty H, Hiltunen M, Knip M, Laakkonen M, Vahasalo P, Karjalainen J, Koskela P, Roivanen M, Leinikki P, Hovi T, Akerblom HK (1995) A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Diabetes 44:652–657Google Scholar
  31. 31.
    Samuelson U, Johansson C, Ludvigsson J (1993) Breast-feeding seems to play a marginal role in the prevention of insulindependent diabetes mellitus. Diabetes Res Clin Pract 19:203–210Google Scholar
  32. 32.
    Virtanen SM, Rasanen L, Ylonen K, Aro A, Clayton D, Langholz B, Pitkaniemi J, Savilahti E, Louranaa R, Tuomilehto J, Akerblom HK (1993) Early introduction of dairy products associated with increased risk of IDDM in Finnish Children. Diabetes 42:1786–1790Google Scholar
  33. 33.
    Verge CF, Howard NJ, Irwig L, Simpson JM, Mackerras D, Silink M (1994) Environmental factors in chilhood diabetes. Diabetes Care 17:1381–1389Google Scholar
  34. 34.
    Gerstein HC (1994) Cow's milk exposure and type I diabetes mellitus: a critical overview of the clinical literature. Diabetes Care 17:13–19Google Scholar
  35. 35.
    Kostraba JN (1994) What can epidemiology tell us about the role of infant diet in the etiology of IDDM. Diabetes Care 17:87–91Google Scholar
  36. 36.
    Virtanen SM, Aro A (1994) Dietary factors in the aetiology of diabetes. Ann Med 26:469–478Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • F. Pérez-Bravo
    • 1
  • E. Carrasco
    • 2
  • M. D. Gutierrez-López
    • 3
  • M. T. Martínez
    • 3
  • G. López
    • 2
  • M. García de los Rios
    • 2
  1. 1.Laboratorio de Bioquímica, Instituto de Nutritión y Tecnología de los AlimentosUniversidad de Chile, MaculSantiagoChile
  2. 2.Unidad de Diabetes y Nutrición, Facultad de Medicina, Campus OccidenteUniversidad de ChileSantiagoChile
  3. 3.Unidad de Lpidos y Aterosclerosis, Hospital Clínico San Carlos, Facultad de MedicinaUniversidad ComplutenseMadridSpain

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