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Reviews in Endocrine and Metabolic Disorders

, Volume 7, Issue 3, pp 149–162 | Cite as

Environmental factors in the development of Type 1 diabetes

  • Hui Peng
  • William Hagopian
Article

Abstract

Environmental factors appear to play an important role in the pathogenesis of childhood-onset type 1 diabetes (T1D). The most important factors are thought to be infectious, dietary, perinatal, and psychosocial. Enteroviruses (especially Coxsackie B virus), breastfeeding, the early presence or lack of certain foods, birth weight, childhood over-nutrition, maternal islet autoimmunity, and negative stress events have been shown to be related to the prevalence of T1D. However, clear conclusions to date are limited because most studies lacked power to detect exposure/disease associations, were not prospective or long-term, did not start in infancy, had imprecise or infrequent exposure estimates, had confounding exposures, and failed to account for genetic susceptibility. In addition to the identification of specific antigenic triggers, several more general hypotheses, including the accelerator and hygiene hypotheses, are testable approaches worth pursuing.

Keywords

Autoimmunity Infectious Dietary Perinatal Psychosocial Nutrition Gene-environment 

Abbreviations

T1D

(type 1 diabetes)

HEV

(human enterovirus)

HLA

(human leukocyte antigen)

GAD

(glutamic acid decarboxylase)

Notes

Acknowledgments

We acknowledge the support of the TEDDY consurtium by NIDDK, NIAID, and JDRF (DK063829) and support of our population-based T1D studies by the Hussman Foundation.

References

  1. 1.
    Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J. Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care 2000;23:1516–26.PubMedGoogle Scholar
  2. 2.
    She JX, Marron MP. Genetic susceptibility factors in type 1 diabetes: linkage, disequilibrium and functional analyses. Curr Opin Immunol 1998;10:682–9.PubMedGoogle Scholar
  3. 3.
    Pugliese A. Unraveling the genetics of insulin-dependent diabetes: the search must go on. Diabetes Rev 1999;7:39–54.Google Scholar
  4. 4.
    Pugliese A. Genetics of type 1 diabetes. Endocrinol Metab Clin North Am 2004;33:1–16, vii.PubMedGoogle Scholar
  5. 5.
    Hyttinen V, Kaprio J, Kinnunen L, Koskenvuo M, Tuomilehto J. Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study. Diabetes 2003;52:1052–5.PubMedGoogle Scholar
  6. 6.
    Barnett AH, Eff C, Leslie RDG, Pyke DA. Diabetes in identical twins:a study of 200 pairs. Diabetologia 1981;20:87–93.PubMedGoogle Scholar
  7. 7.
    Kumar D, Gemayel N, Deapen D, Kapadia D, Yamashita P, Lee M, Dwyer J, Roy-Burman P, Bray G, Mack T. North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin. Diabetes 1993;42:1351–63.PubMedGoogle Scholar
  8. 8.
    Tillil H, Köbberling J. Age-corrected empirical genetic risk estimates for first-degree relatives of IDDM patients. Diabetes 1987;36:93–9.PubMedGoogle Scholar
  9. 9.
    el-Hashimy M, Angelico MC, Martin BC, Krolewski AS, Warram JH. Factors modifying the risk of IDDM in offspring of an IDDM parent. Diabetes 1995;44:295–9.PubMedGoogle Scholar
  10. 10.
    Onkamo P, Vaananen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of Type I diabetes-the analysis of the data on published incidence trends. Diabetologia 1999;42:1395–403.PubMedGoogle Scholar
  11. 11.
    Gale EA. The rise of childhood type 1 diabetes in the 20th century. Diabetes 2002;51:3353–61.PubMedGoogle Scholar
  12. 12.
    Soltesz G. Diabetes in the young: a paediatric and epidemiological perspective. Diabetologia 2003;46:447–54.PubMedGoogle Scholar
  13. 13.
    Haynes A, Bower C, Bulsara M, Jones T, Davis E. Continued increase in the incidence of childhood Type 1 diabetes in a population-based Australian sample (1985–2002). Diabetologia 2004;47:866–70.PubMedGoogle Scholar
  14. 14.
    Pundziute-Lycka A, Dahlquist G, Nystrom L, Arnqvist H, Bjork E, Blohme G, Bolinder J, Eriksson JW, Sundkvist G, Ostman J, And The Swedish Childhood Diabetes Study G. The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0–34 years group in Sweden 1983 to 1998. Diabetologia 2002;45:783–91.PubMedGoogle Scholar
  15. 15.
    Weets I, De Leeuw IH, Du Caju MV, Rooman R, Keymeulen B, Mathieu C, Rottiers R, Daubresse JC, Rocour-Brumioul D, Pipeleers DG, Gorus FK. The incidence of type 1 diabetes in the age group 0–39 years has not increased in Antwerp (Belgium) between 1989 and 2000: evidence for earlier disease manifestation. Diabetes Care 2002;25:840–6.PubMedGoogle Scholar
  16. 16.
    Dahlquist G, Mustonen L. Analysis of 20 years of prospective registration of childhood onset diabetes time trends and birth cohort effects. Swedish Childhood Diabetes Study Group. Acta Paediatr 2000;89:1231–7.PubMedGoogle Scholar
  17. 17.
    Kondrashova A, Reunanen A, Romanov A, Karvonen A, Viskari H, Vesikari T, Ilonen J, Knip M, Hyoty H. A six-fold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med 2005;37:67–72.PubMedGoogle Scholar
  18. 18.
    Rewers M, LaPorte RE, Walczak M, Dmochowski K, Bogaczynska E. Apparent epidemic of insulin-dependent diabetes mellitus in Midwestern Poland. Diabetes 1987;36:106–13.PubMedGoogle Scholar
  19. 19.
    Wagenkneckt LE, Roseman JM, Herman WH. Increased incidence of insulin-dependent diabetes mellitus following an epidemic of coxsackie virus B5. Am J Epidemiol 1991;132:1024–31.Google Scholar
  20. 20.
    Tull ES, Roseman JM, Christian CL. Epidemiology of childhood IDDM in U.S. Virgin Islands from 1979 to 1988. Evidence of an epidemic in early 1980s and variation by degree of racial admixture. Diabetes Care 1991;14:558–64.PubMedGoogle Scholar
  21. 21.
    Dokheel TM. An epidemic of childhood diabetes in the United States? Evidence from Allegheny County, Pennsylvania. Pittsburgh Diabetes Epidemiology Research Group. Diabetes Care 1993;16:1606–11.PubMedGoogle Scholar
  22. 22.
    Yang Z, Long X, Shen J, Liu D, Dorman JS, Laporte RE, Chang YF. Epidemics of type 1 diabetes in China. Pediatr Diabetes 2005;6:122–8.PubMedGoogle Scholar
  23. 23.
    Bodington MJ, Muzulu SI, Burden AC. Spatial clustering in childhood diabetes: evidence of an environmental cause. Diabet Med 1995;12:865–7.PubMedGoogle Scholar
  24. 24.
    Knip M. Environmental triggers and determinants of beta-cell autoimmunity and type 1 diabetes. Rev Endocr Metab Disord 2003;4:213–23.PubMedGoogle Scholar
  25. 25.
    Knip M, Veijola R, Virtanen SM, Hyoty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes 2005;54 Suppl 2:S125–36.PubMedGoogle Scholar
  26. 26.
    Like AA, Rossini AA. Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 1976;193:415–7.PubMedGoogle Scholar
  27. 27.
    Kolb-Bachofen V, Epstein S, Kiesel U, Kolb H. Low-dose streptozocin-induced diabetes in mice. Electron microscopy reveals single-cell insulitis before diabetes onset. Diabetes 1988;37:21–7.PubMedGoogle Scholar
  28. 28.
    Yoon JW, Austin M, Onodera T, Notkins AL. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 1979;300:1173–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Hashimoto K, Yasukawa M, Tohyama M. Human herpesvirus 6 and drug allergy. Curr Opin Allergy Clin Immunol 2003;3:255–60.PubMedGoogle Scholar
  30. 30.
    Kaufman DJ, Erlander MG, Clare-Salzer M, Atkinson MA, Maclaren NK, Tobin AJ. Autoimmunity to two forms of glutamate decarboxylase in Insulin-dependent diabetes mellitus. J Clin Invest 1992;89:283–92.PubMedGoogle Scholar
  31. 31.
    Ellerman KE, Richards CA, Guberski DL, Shek WR, Like AA. Kilham rat triggers T-cell-dependent autoimmune diabetes in multiple strains of rat. Diabetes 1996;45:557–62.PubMedGoogle Scholar
  32. 32.
    Fujinami RS. Viruses and autoimmune disease-two sides of the same coin? Trends Microbiol 2001;9:377–81.PubMedGoogle Scholar
  33. 33.
    Hyoty H. Enterovirus infections and type 1 diabetes. Ann Med 2002;34:138–47.PubMedGoogle Scholar
  34. 34.
    Jun HS, Yoon JW. A new look at viruses in type 1 diabetes. Diabetes Metab Res Rev 2003;19:8–31.PubMedGoogle Scholar
  35. 35.
    Lammi N, Karvonen M, Tuomilehto J. Do microbes have a causal role in type 1 diabetes? Med Sci Monit 2005;11:RA63–9.PubMedGoogle Scholar
  36. 36.
    Roivainen M. Enteroviruses: new findings on the role of enteroviruses in type 1 diabetes. Int J Biochem Cell Biol 2006;38:721–5.PubMedGoogle Scholar
  37. 37.
    Filippi C, von Herrath M. How viral infections affect the autoimmune process leading to type 1 diabetes. Cell Immunol 2005;233:125–32.PubMedGoogle Scholar
  38. 38.
    Fujinami RS, von Herrath MG, Christen U, Whitton JL. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev 2006;19:80–94.PubMedGoogle Scholar
  39. 39.
    Ginsberg-Fellner F, Witt ME, Yagihashi S, Dobersen MJ, Taub F, Fedun B, McEvoy RC, Roman SH, Davies TF, Cooper LZ, Rubinstein P, Notkins AL. Congenital rubella syndrome as a model for Type 1 (insulin-dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies. Diabetologia 1984;27:87–9.PubMedGoogle Scholar
  40. 40.
    Jenson AB, Rosenberg HS, Notkins AL. Pancreatic islet-cell damage in children with fatal viral infections. Lancet 1980;2:354–8.PubMedGoogle Scholar
  41. 41.
    Banatvala JE, Schernthaner G, Schober E, De Silva LM, Bryant J, Borkenstein M, Brown D, Menser MA. Coxsackie B, mumps, rubella and cytomegalovirus specific IgM response in patients with juvenile-onset diabetes mellitus in Britain, Austria and Australia. Lancet 1985;ii:1409–12.Google Scholar
  42. 42.
    Helmke K, Otten A, Willems W. Islet cell antibodies in children with mumps infection. Lancet 1980;ii:211–2.Google Scholar
  43. 43.
    Otonkoski T, Roivainen M, Vaarala O, Dinesen B, Leipala JA, Hovi T, Knip M. Neonatal Type I diabetes associated with maternal echovirus 6 infection: a case report. Diabetologia 2000;43:1235–8.PubMedGoogle Scholar
  44. 44.
    Cabrera-Rode E, Sarmiento L, Tiberti C, Molina G, Barrios J, Hernandez D, Diaz-Horta O, Di Mario U. Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16. Diabetologia 2003;46:1348–53.PubMedGoogle Scholar
  45. 45.
    Yasumoto N, Hara M, Kitamoto Y, Nakayama M, Sato T. Cytomegalovirus infection associated with acute pancreatitis, rhabdomyolysis and renal failure. Intern Med 1992;31:426–30.PubMedGoogle Scholar
  46. 46.
    Ivarsson SA, Lindberg B, Nilsson KO, Ahlfors K, Svanberg L. The prevalence of type 1 diabetes mellitus at follow-up of Swedish infants congenitally infected with cytomegalovirus. Diabet Med 1993;10:521–3.PubMedGoogle Scholar
  47. 47.
    Roivainen M, Rasilainen S, Ylipaasto P, Nissinen R, Ustinov J, Bouwens L, Eizirik DL, Hovi T, Otonkoski T. Mechanisms of coxsackievirus-induced damage to human pancreatic beta-cells. J Clin Endocrinol Metab 2000;85:432–40.PubMedGoogle Scholar
  48. 48.
    Chikazawa K, Okusa H, Minakami H, Kimura K, Araki S, Tamada T. [Acute onset of insulin-dependent diabetes mellitus caused by Epstein-Barr virus infection]. Nippon Sanka Fujinka Gakkai Zasshi 1985;37:453–6.PubMedGoogle Scholar
  49. 49.
    Surcel HM, Ilonen J, Kaar ML, Hyoty H, Leinikki P. Infection by multiple viruses and lymphocyte abnormalities at the diagnosis of diabetes. Acta Paediatr Scand 1988;77:471–4.PubMedGoogle Scholar
  50. 50.
    Conrad B, Weissmahr RN, Boni J, Arcari R, Schupbach J, Mach B. A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes. Cell 1997;90:303–13.PubMedGoogle Scholar
  51. 51.
    Honeyman MC, Coulson BS, Stone NL, Gellert SA, Goldwater PN, Steele CE, Couper JJ, Tait BD, Colman PG, Harrison LC. Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. Diabetes 2000;49:1319–24.PubMedGoogle Scholar
  52. 52.
    Onitilo AA, Shaw GR. Parvovirus B19 infection in an isolated pancreas transplant recipient. Transplant Proc 2005;37:4433–5.PubMedGoogle Scholar
  53. 53.
    Munakata Y, Kodera T, Saito T, Sasaki T. Rheumatoid arthritis, type 1 diabetes, and Graves’ disease after acute parvovirus B19 infection. Lancet 2005;366:780.PubMedGoogle Scholar
  54. 54.
    Makela M, Vaarala O, Hermann R, Salminen K, Vahlberg T, Veijola R, Hyoty H, Knip M, Simell O, Ilonen J. Enteral virus infections in early childhood and an enhanced type 1 diabetes-associated antibody response to dietary insulin. J Autoimmun 2006.Google Scholar
  55. 55.
    Vaarala O. The gut immune system and type 1 diabetes. Ann N Y Acad Sci 2002;958:39–46.PubMedCrossRefGoogle Scholar
  56. 56.
    Calcinaro F, Dionisi S, Marinaro M, Candeloro P, Bonato V, Marzotti S, Corneli RB, Ferretti E, Gulino A, Grasso F, De Simone C, Di Mario U, Falorni A, Boirivant M, Dotta F. Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia 2005;48:1565–75.PubMedGoogle Scholar
  57. 57.
    Foulis AK, Farquharson MA, Cameron SO, McGill M, Schönke H, Kandolff R. A search for the presence of the enteroviral capsid protein VP1 in pancreases of patients with type 1 (insulin-dependent) diabetes and pancreases and hearts of infants who died of coxsackieviral myocarditis. Diabetologia 1990;33:290–8.PubMedGoogle Scholar
  58. 58.
    Ylipaasto P, Klingel K, Lindberg AM, Otonkoski T, Kandolf R, Hovi T, Roivainen M. Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia 2004;47:225–39.PubMedGoogle Scholar
  59. 59.
    Frisk G, Tuvemo T. Enterovirus infections with beta-cell tropic strains are frequent in siblings of children diagnosed with type 1 diabetes children and in association with elevated levels of GAD65 antibodies. J Med Virol 2004;73:450–9.PubMedGoogle Scholar
  60. 60.
    Hindersson M, Elshebani A, Orn A, Tuvemo T, Frisk G. Simultaneous type 1 diabetes onset in mother and son coincident with an enteroviral infection. J Clin Virol 2005;33:158–67.PubMedGoogle Scholar
  61. 61.
    Hiltunen M, Hyoty H, Knip M, Ilonen J, Reijonen H, Vahasalo P, Roivainen M, Lonnrot M, Leinikki P, Hovi T, Akerblom HK. Islet cell antibody seroconversion in children is temporally associated with enterovirus infections. Childhood Diabetes in Finland (DiMe) Study Group. J Infect Dis 1997;175:554–60.PubMedGoogle Scholar
  62. 62.
    Lonnrot M, Korpela K, Knip M, Ilonen J, Simell O, Korhonen S, Savola K, Muona P, Simell T, Koskela P, Hyoty H. Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study. Diabetes 2000;49:1314–8.PubMedGoogle Scholar
  63. 63.
    Lonnrot M, Salminen K, Knip M, Savola K, Kulmala P, Leinikki P, Hyypia T, Akerblom HK, Hyoty H. Enterovirus RNA in serum is a risk factor for beta-cell autoimmunity and clinical type 1 diabetes: a prospective study. Childhood Diabetes in Finland (DiMe) Study Group. J Med Virol 2000;61:214–20.PubMedGoogle Scholar
  64. 64.
    Salminen KK, Vuorinen T, Oikarinen S, Helminen M, Simell S, Knip M, Ilonen J, Simell O, Hyoty H. Isolation of enterovirus strains from children with preclinical Type 1 diabetes. Diabet Med 2004;21:156–64.PubMedGoogle Scholar
  65. 65.
    Sadeharju K, Hamalainen AM, Knip M, Lonnrot M, Koskela P, Virtanen SM, Ilonen J, Akerblom HK, Hyoty H. Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial. Clin Exp Immunol 2003;132:271–7.PubMedGoogle Scholar
  66. 66.
    Graves PM, Rotbart HA, Nix WA, Pallansch MA, Erlich HA, Norris JM, Hoffman M, Eisenbarth GS, Rewers M. Prospective study of enteroviral infections and development of beta-cell autoimmunity. Diabetes autoimmunity study in the young (DAISY). Diabetes Res Clin Pract 2003;59:51–61.PubMedGoogle Scholar
  67. 67.
    Fuchtenbusch M, Irnstetter A, Jager G, Ziegler AG. No evidence for an association of coxsackie virus infections during pregnancy and early childhood with development of islet autoantibodies in offspring of mothers or fathers with Type 1 diabetes. J Autoimmun 2001;17:333–40.PubMedGoogle Scholar
  68. 68.
    Dahlquist G. Environmental risk factors in human type 1 diabetes—an epidemiological perspective. Diabetes Metab Rev 1995;11:37–46.PubMedGoogle Scholar
  69. 69.
    Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001;358:221–9.PubMedGoogle Scholar
  70. 70.
    Rothe H, Ito Y, Kolb H. Disease resistant, NOD-related strains reveal checkpoints of immunoregulation in the pancreas. J Mol Med 2001;79:190–7.PubMedGoogle Scholar
  71. 71.
    Green J, Casabonne D, Newton R. Coxsackie B virus serology and Type 1 diabetes mellitus: a systematic review of published case-control studies. Diabet Med 2004;21:507–14.PubMedGoogle Scholar
  72. 72.
    Craig ME, Howard NJ, Silink M, Rawlinson WD. Reduced frequency of HLA DRB1*03-DQB1*02 in children with type 1 diabetes associated with enterovirus RNA. J Infect Dis 2003;187:1562–70.PubMedGoogle Scholar
  73. 73.
    Yin H, Berg AK, Tuvemo T, Frisk G. Enterovirus RNA is found in peripheral blood mononuclear cells in a majority of type 1 diabetic children at onset. Diabetes 2002;51:1964–71.PubMedGoogle Scholar
  74. 74.
    Foulis AK, McGill M, Farquharson MA, Hilton DA. A search for evidence of viral infection in pancreases of newly diagnosed patients with IDDM. Diabetologia 1997;40:53–61.PubMedGoogle Scholar
  75. 75.
    Gale EA, Atkinson M. A piece of nucleic acid surrounded by controversy: coxsackievirus and the causes of Type 1 diabetes. Diabet Med 2004;21:503–6.PubMedGoogle Scholar
  76. 76.
    Forrest JM, Menser MA, Burgess JA. High frequency of diabetes mellitus in young adults with congenital rubella. Lancet 1971;2:332–4.PubMedGoogle Scholar
  77. 77.
    Johnson GM, Tudor RB. Diabetes mellitus and congenital rubella infection. Am J Dis Child 1970;120:453–5.PubMedGoogle Scholar
  78. 78.
    Plotkin SA, Kaye R, Forrest JM, Menser MA, Harley JD. Diabetes mellitus and congenital rubella. Pediatrics 1970;46:650–1.PubMedGoogle Scholar
  79. 79.
    Forrest JM, Menser MA, Harley JD. Diabetes mellitus and congenital rubella. Pediatrics 1969;44:445–7.PubMedGoogle Scholar
  80. 80.
    Menser MA, Forrest JM, Bransby RD. Rubella infection and diabetes mellitus. Lancet 1978;i:57–60.Google Scholar
  81. 81.
    Ginsberg-Fellner F, Witt ME, Fedun B, Taub F, Dobersen MJ, McEvoy RC, Cooper LZ, Notkins AL, Rubinstein P. Diabetes mellitus and autoimmunity in patients with the congenital rubella syndrome. Rev Infect Dis 1985;7 Suppl 1:S170–6.PubMedGoogle Scholar
  82. 82.
    Conrad B, Weidmann E, Trucco G, Rudert WA, Behboo R, Ricordi C, Rodriquez-Rilo H, Finegold D, Trucco M. Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology. Nature 1994;371:351–5.PubMedGoogle Scholar
  83. 83.
    Lernmark Å, Li S, Baekkeskov S, Christie M, Michelsen B, Ursing J, Landin-Olsson M, Sundkvist G. Islet-specific immune mechanisms. Diabetes Metab Rev 1987;3:959–80.PubMedCrossRefGoogle Scholar
  84. 84.
    von Herrath MG, Fujinami RS, Whitton JL. Microorganisms and autoimmunity: making the barren field fertile? Nat Rev Microbiol 2003;1:151–7.Google Scholar
  85. 85.
    Schubert C. The worm has turned. Nat Med 2004;10:1271–2.PubMedGoogle Scholar
  86. 86.
    Bach JF. Protective role of infections and vaccinations on autoimmune diseases. J Autoimmun 2001;16:347–53.PubMedGoogle Scholar
  87. 87.
    Pundziute-Lycka A, Urbonaite B, Dahlquist G. Infections and risk of Type I (insulin-dependent) diabetes mellitus in Lithuanian children. Diabetologia 2000;43:1229–34.PubMedGoogle Scholar
  88. 88.
    Viskari HR, Koskela P, Lonnrot M, Luonuansuu S, Reunanen A, Baer M, Hyoty H. Can enterovirus infections explain the increasing incidence of type 1 diabetes? Diabetes Care 2000;23:414–6.PubMedGoogle Scholar
  89. 89.
    Heino L, Lonnrot M, Knip M, Kupila A, Erkkila S, Toivonen A, Vahasalo P, Ilonen J, Simell O, Hyoty H. No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children. Clin Exp Immunol 2001;126:432–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Lonnrot M, Knip M, Marciulionyte D, Rahko J, Urbonaite B, Moore WP, Vilja P, Hyoty H. Enterovirus antibodies in relation to islet cell antibodies in two populations with high and low incidence of type 1 diabetes. Diabetes Care 1999;22:2086–8.PubMedGoogle Scholar
  91. 91.
    Gibbon C, Smith T, Egger P, Betts P, Phillips D. Early infection and subsequent insulin dependent diabetes. Arch Dis Child 1997;77:384–5.PubMedGoogle Scholar
  92. 92.
    Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation. EURODIAB Substudy 2 Study Group. Diabetologia 2000;43:47–53.Google Scholar
  93. 93.
    Oldstone MB. Prevention of type I diabetes in nonobese diabetic mice by virus infection. Science 1988;239:500–2.PubMedGoogle Scholar
  94. 94.
    Hermitte L, Vialettes B, Naquet P, Atlan C, Payan MJ, Vague P. Paradoxical lessening of autoimmune processes in non-obese diabetic mice after infection with the diabetogenic variant of encephalomyocarditis virus. Eur J Immunol 1990;20:1297–303.PubMedGoogle Scholar
  95. 95.
    Wilberz S, Partke HJ, Dagnaes-Hansen F, Herberg L. Persistent MHV (mouse hepatitis virus) infection reduces the incidence of diabetes mellitus in non-obese diabetic mice. Diabetologia 1991;34:2–5.PubMedGoogle Scholar
  96. 96.
    Takei I, Asaba Y, Kasatani T, Maruyama T, Watanabe K, Yanagawa T, Saruta T, Ishii T. Suppression of development of diabetes in NOD mice by lactate dehydrogenase virus infection. J Autoimmun 1992;5:665–73.PubMedGoogle Scholar
  97. 97.
    Tracy S, Drescher KM, Chapman NM, Kim KS, Carson SD, Pirruccello S, Lane PH, Romero JR, Leser JS. Toward testing the hypothesis that group B coxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabetic mice with CVB markedly lowers diabetes incidence. J Virol 2002;76:12097–111.PubMedGoogle Scholar
  98. 98.
    Gale EA. A missing link in the hygiene hypothesis? Diagetologia 2002;588–94.Google Scholar
  99. 99.
    Anderson WJ, Watson L. Conclusions about type 1 diabetes and hygiene hypothesis are premature. Bmj 2001;322:1429.PubMedGoogle Scholar
  100. 100.
    van Schayck CP, Knottnerus JA. Can the ‘hygiene hypothesis’ be explained by confounding by behavior? J Clin Epidemiol 2004;57:435–7.PubMedGoogle Scholar
  101. 101.
    Sheikh A, Smeeth L, Hubbard R. There is no evidence of an inverse relationship between TH2-mediated atopy and TH1-mediated autoimmune disorders: Lack of support for the hygiene hypothesis. J Allergy Clin Immunol 2003;111:131–5.PubMedGoogle Scholar
  102. 102.
    Virtanen SM, Knip M. Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a young age. Am J Clin Nutr 2003;78:1053–67.PubMedGoogle Scholar
  103. 103.
    Lefebvre DE, Powell KL, Strom A, Scott FW. Dietary proteins as environmental modifiers of type 1 diabetes mellitus. Annu Rev Nutr 2006;26:175–202.PubMedGoogle Scholar
  104. 104.
    Visalli N, Sebastiani L, Adorisio E, Conte A, De Cicco AL, D’Elia R, Manfrini S, Pozzilli P. Environmental risk factors for T1D in Rome and province. Arch Dis Child 2003;88:695–8.PubMedGoogle Scholar
  105. 105.
    Sipetic S, Vlajinac H, Kocev N, Bjekic M, Sajic S. Early infant diet and risk of type 1 diabetes mellitus in Belgrade children. Nutrition 2005;21:474–9.PubMedGoogle Scholar
  106. 106.
    Malcova H, Sumnik Z, Drevinek P, Venhacova J, Lebl J, Cinek O. Absence of breast-feeding is associated with the risk of type 1 diabetes: a case-control study in a population with rapidly increasing incidence. Eur J Pediatr 2006;165:114–9.PubMedGoogle Scholar
  107. 107.
    Sadauskaite-Kuehne V, Ludvigsson J, Padaiga Z, Jasinskiene E, Samuelsson U. Longer breastfeeding is an independent protective factor against development of type 1 diabetes mellitus in childhood. Diabetes Metab Res Rev 2004;20:150–7.PubMedGoogle Scholar
  108. 108.
    Wahlberg J, Fredriksson J, Nikolic E, Vaarala O, Ludvigsson J. Environmental factors related to the induction of beta-cell autoantibodies in 1-yr-old healthy children. Pediatr Diabetes 2005;6:199–205.PubMedGoogle Scholar
  109. 109.
    Wahlberg J, Vaarala O, Ludvigsson J. Dietary risk factors for the emergence of type 1 diabetes-related autoantibodies in 21/2 year-old Swedish children. Br J Nutr 2006;95:603–8.PubMedGoogle Scholar
  110. 110.
    Virtanen SM, Laara E, Hypponen E, Reijonen H, Rasanen L, Aro A, Knip M, Ilonen J, Akerblom HK. Cow’s milk consumption, HLA-DQB1 genotype, and type 1 diabetes: a nested case-control study of siblings of children with diabetes. Childhood diabetes in Finland study group. Diabetes 2000;49:912–7.PubMedGoogle Scholar
  111. 111.
    Marshall AL, Chetwynd A, Morris JA, Placzek M, Smith C, Olabi A, Thistlethwaite D. Type 1 diabetes mellitus in childhood: a matched case control study in Lancashire and Cumbria, UK. Diabet Med 2004;21:1035–40.PubMedGoogle Scholar
  112. 112.
    Vaarala O, Knip M, Paronen J, Hamalainen AM, Muona P, Vaatainen M, Ilonen J, Simell O, Akerblom HK. Cow’s milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes. Diabetes 1999;48:1389–94.PubMedGoogle Scholar
  113. 113.
    Norris JM, Beaty B, Klingensmith G, Yu L, Hoffman M, Chase HP, Erlich HA, Hamman RF, Eisenbarth GS, Rewers M. Lack of association between early exposure to cow’s milk protein and beta-cell autoimmunity. Diabetes Autoimmunity Study in the Young (DAISY). Jama 1996;276:609–14.PubMedGoogle Scholar
  114. 114.
    Norris JM, Barriga K, Klingensmith GH, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. Jama 2003;290:1713–20.PubMedGoogle Scholar
  115. 115.
    Hummel M, Fuchtenbusch M, Schenker M, Ziegler AG. No major association of breast-feeding, vaccinations, and childhood viral diseases with early islet autoimmunity in the German BABYDIAB Study. Diabetes Care 2000;23:969–74.PubMedGoogle Scholar
  116. 116.
    Ziegler AG, Schmid S, Huber D, Hummel M, Bonifacio E. Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. Jama 2003;290:1721–8.PubMedGoogle Scholar
  117. 117.
    Couper JJ, Steele C, Beresford S, Powell T, McCaul K, Pollard A, Gellert S, Tait B, Harrison LC, Colman PG. Lack of association between duration of breast-feeding or introduction of cow’s milk and development of islet autoimmunity. Diabetes 1999;48:2145–9.PubMedGoogle Scholar
  118. 118.
    Gerstein HC. Cow’s milk exposure and type I diabetes mellitus. A critical overview of the clinical literature. Diabetes Care 1994;17:13–9.PubMedGoogle Scholar
  119. 119.
    Kimpimaki T, Erkkola M, Korhonen S, Kupila A, Virtanen SM, Ilonen J, Simell O, Knip M. Short-term exclusive breastfeeding predisposes young children with increased genetic risk of Type I diabetes to progressive beta-cell autoimmunity. Diabetologia 2001;44:63–9.PubMedGoogle Scholar
  120. 120.
    Virtanen SM, Kenward MG, Erkkola M, Kautiainen S, Kronberg-Kippila C, Hakulinen T, Ahonen S, Uusitalo L, Niinisto S, Veijola R, Simell O, Ilonen J, Knip M. Age at introduction of new foods and advanced beta cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes. Diabetologia 2006;49:1512–21.PubMedGoogle Scholar
  121. 121.
    Erkkola M, Pigg HM, Virta-Autio P, Hekkala A, Hypponen E, Knip M, Virtanen SM. Infant feeding patterns in the Finnish type I diabetes prediction and prevention nutrition study cohort. Eur J Clin Nutr 2005;59:107–13.PubMedGoogle Scholar
  122. 122.
    Harrison LC, Honeyman MC. Cow’s milk and type 1 diabetes: the real debate is about mucosal immune function. Diabetes 1999;48:1501–7.PubMedGoogle Scholar
  123. 123.
    Kolb H, Pozzilli P. Cow’s milk and type I diabetes: the gut immune system deserves attention. Immunol Today 1999;20:108–10.PubMedGoogle Scholar
  124. 124.
    Vaarala O. Gut and the induction of immune tolerance in type 1 diabetes. Diabetes Metab Res Rev 1999;15:353–61.PubMedGoogle Scholar
  125. 125.
    Vaarala O. Is type 1 diabetes a disease of the gut immune system triggered by cow’s milk insulin? Adv Exp Med Biol 2005;569:151–6.PubMedCrossRefGoogle Scholar
  126. 126.
    Schmid S, Buuck D, Knopff A, Bonifacio E, Ziegler AG. BABYDIET, a feasibility study to prevent the appearance of islet autoantibodies in relatives of patients with Type 1 diabetes by delaying exposure to gluten. Diabetologia 2004;47:1130–1.PubMedGoogle Scholar
  127. 127.
    Ludvigsson JF, Ludvigsson J, Ekbom A, Montgomery SM. Celiac disease and risk of subsequent T1D: a general population cohort study of children and adolescents. Diabetes Care 2006;29:2483–8.PubMedGoogle Scholar
  128. 128.
    Harris SS. Vitamin D in type 1 diabetes prevention. J Nutr 2005;135:323–5.PubMedGoogle Scholar
  129. 129.
    Zella JB, DeLuca HF. Vitamin D and autoimmune diabetes. J Cell Biochem 2003;88:216–22.PubMedGoogle Scholar
  130. 130.
    Mathieu C, Badenhoop K. Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab 2005;16:261–6.PubMedGoogle Scholar
  131. 131.
    Mathieu C, van Etten E, Decallonne B, Guilietti A, Gysemans C, Bouillon R, Overbergh L. Vitamin D and 1,25-dihydroxyvitamin D3 as modulators in the immune system. J Steroid Biochem Mol Biol 2004;89–90:449–52.PubMedGoogle Scholar
  132. 132.
    Gysemans CA, Cardozo AK, Callewaert H, Giulietti A, Hulshagen L, Bouillon R, Eizirik DL, Mathieu C. 1,25-Dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes in nonobese diabetic mice. Endocrinology 2005;146:956–64.PubMedGoogle Scholar
  133. 133.
    Stene LC, Joner G. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset T1D: a large, population-based, case-control study. Am J Clin Nutr 2003;78:1128–34.PubMedGoogle Scholar
  134. 134.
    Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group. Diabetologia 1999;42:51–4.Google Scholar
  135. 135.
    Stene LC, Ulriksen J, Magnus P, Joner G. Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring. Diabetologia 2000;43:1093–8.PubMedGoogle Scholar
  136. 136.
    Ksiazyk J. [Current views on requirements for vitamin D, calcium and phosphorus, particularly in formula fed infants]. Med Wieku Rozwoj 2000;4:423–30.PubMedGoogle Scholar
  137. 137.
    Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001;358:1500–3.PubMedGoogle Scholar
  138. 138.
    Knekt P, Reunanen A, Marniemi J, Leino A, Aromaa A. Low vitamin E status is a potential risk factor for insulin-dependent diabetes mellitus. J Intern Med 1999;245:99–102.PubMedGoogle Scholar
  139. 139.
    Myers MA, Hettiarachchi KD, Ludeman JP, Wilson AJ, Wilson CR, Zimmet PZ. Dietary microbial toxins and type 1 diabetes. Ann N Y Acad Sci 2003;1005:418–22.PubMedGoogle Scholar
  140. 140.
    Hathout EH, Beeson WL, Ischander M, Rao R, Mace JW. Air pollution and type 1 diabetes in children. Pediatr Diabetes 2006;7:81–7.PubMedGoogle Scholar
  141. 141.
    Dahlquist GG, Blom LG, Persson L-Å, Sandström AIM, SGI W. Dietary factors and the risk of developing insulin dependent diabetes in childhood. BMJ 1990;300:1302–6.PubMedGoogle Scholar
  142. 142.
    Pundziute-Lycka A, Persson LA, Cedermark G, Jansson-Roth A, Nilsson U, Westin V, Dahlquist G. Diet, growth, and the risk for type 1 diabetes in childhood: a matched case-referent study. Diabetes Care 2004;27:2784–9.PubMedGoogle Scholar
  143. 143.
    Mitchell ML, Quinn M, Orban T, Hermos RJ. Failure to find GAD antibodies at birth in children with diabetes. Diabetes Care 1998;21:197–8.PubMedGoogle Scholar
  144. 144.
    Naserke HE, Bonifacio E, Ziegler AG. Immunoglobulin G insulin autoantibodies in BABYDIAB offspring appear postnatally: sensitive early detection using a protein A/G-based radiobinding assay. J Clin Endocrinol Metab 1999;84:1239–43.PubMedGoogle Scholar
  145. 145.
    Hamalainen AM, Ronkainen MS, Akerblom HK, Knip M. Postnatal elimination of transplacentally acquired disease-associated antibodies in infants born to families with type 1 diabetes. The Finnish TRIGR Study Group. Trial to reduce IDDM in the genetically at risk. J Clin Endocrinol Metab 2000;85:4249–53.PubMedGoogle Scholar
  146. 146.
    Bonfanti R, Bazzigaluppi E, Meschi F, Bognetti E, Riva M, Bosi E, Chiumello G, Bonifacio E. Is islet autoimmunity really detectable at birth? Diabetologia 1999;42:1442–3.PubMedGoogle Scholar
  147. 147.
    Lindberg B, Ivarsson SA, Landin-Olsson M, Sundkvist G, Svanberg L, Lernmark A. Islet autoantibodies in cord blood from children who developed type I (insulin-dependent) diabetes mellitus before 15 years of age. Diabetologia 1999;42:181–7.PubMedGoogle Scholar
  148. 148.
    DeStefano F, Mullooly JP, Okoro CA, Chen RT, Marcy SM, Ward JI, Vadheim CM, Black SB, Shinefield HR, Davis RL, Bohlke K. Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus. Pediatrics 2001;108:E112.PubMedGoogle Scholar
  149. 149.
    Dahlquist G, Kallen B: Maternal-child blood group incompatibility and other perinatal events increase the risk for early-onset type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1992;35:671–5.PubMedGoogle Scholar
  150. 150.
    Wagener DK, LaPorte RE, Orchard TJ, Cavender D, Kuller LH, Drash AL. The Pittsburgh diabetes mellitus study. 3: an increased prevalence with older maternal age. Diabetologia 1983;25:82–5.PubMedGoogle Scholar
  151. 151.
    Patterson CC, Carson DJ, Hadden DR, Waugh NR, Cole SK. A case-control investigation of perinatal risk factors for childhood IDDM in Northern Ireland and Scotland. Diabetes Care 1994;17:376–81.PubMedGoogle Scholar
  152. 152.
    Svensson J, Carstensen B, Mortensen HB, Borch-Johnsen K. Early childhood risk factors associated with type 1 diabetes—is gender important? Eur J Epidemiol 2005;20:429–34.PubMedGoogle Scholar
  153. 153.
    Stene LC, Barriga K, Norris JM, Hoffman M, Klingensmith G, Erlich HA, Eisenbarth GS, Rewers M. Symptoms of common maternal infections in pregnancy and risk of islet autoimmunity in early childhood. Diabetes Care 2003;26:3136–41.PubMedGoogle Scholar
  154. 154.
    Stene LC, Barriga K, Norris JM, Hoffman M, Erlich HA, Eisenbarth GS, McDuffie RS Jr, Rewers M. Perinatal factors and development of islet autoimmunity in early childhood: the diabetes autoimmunity study in the young. Am J Epidemiol 2004;160:3–10.PubMedGoogle Scholar
  155. 155.
    Dahlquist GG, Patterson C, Soltesz G. Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group. Diabetes Care 1999;22:1698–702.PubMedGoogle Scholar
  156. 156.
    Stene LC, Magnus P, Lie RT, Sovik O, Joner G. No association between preeclampsia or cesarean section and incidence of type 1 diabetes among children: a large, population-based cohort study. Pediatr Res 2003;54:487–90.PubMedGoogle Scholar
  157. 157.
    McKinney PA, Parslow R, Gurney K, Law G, Bodansky HJ, Williams DR. Antenatal risk factors for childhood diabetes mellitus; a case-control study of medical record data in Yorkshire, UK. Diabetologia 1997;40:933–9.PubMedGoogle Scholar
  158. 158.
    Bingley PJ, Douek IF, Rogers CA, Gale EA: Influence of maternal age at delivery and birth order on risk of type 1 diabetes in childhood: prospective population based family study. Bart’s-Oxford Family Study Group. BMJ 2000;321:420–4.PubMedGoogle Scholar
  159. 159.
    Bottini N, Meloni GF, Lucarelli P, Amante A, Saccucci P, Gloria-Bottini F, Bottini E. Risk of type 1 diabetes in childhood and maternal age at delivery, interaction with ACP1 and sex. Diabetes Metab Res Rev 2005;21:353–8.PubMedGoogle Scholar
  160. 160.
    Cardwell CR, Carson DJ, Patterson CC: Parental age at delivery, birth order, birth weight and gestational age are associated with the risk of childhood Type 1 diabetes: a UK regional retrospective cohort study. Diabet Med 2005;22:200–6.PubMedGoogle Scholar
  161. 161.
    Polanska J, Jarosz-Chobot P. Maternal age at delivery and order of birth are risk factors for type 1 diabetes mellitus in Upper Silesia, Poland. Med Sci Monit 2006;12:CR173–6.PubMedGoogle Scholar
  162. 162.
    Sumnik Z, Drevinek P, Lanska V, Malcova H, Vavrinec J, Cinek O. Higher maternal age at delivery, and lower birth orders are associated with increased risk of childhood type 1 diabetes mellitus. Exp Clin Endocrinol Diabetes 2004;112:294–7.PubMedGoogle Scholar
  163. 163.
    Byrnes G. Maternal age and risk of type 1 diabetes in children. Flawed analysis invalidates conclusions. BMJ 2001;322:1489. (author reply 1490–1481)PubMedGoogle Scholar
  164. 164.
    Lindberg B, Ivarsson SA, Lernmark A. Islet autoantibodies in cord blood could be a risk factor for future diabetes. Diabetologia 1999;42:1375.PubMedGoogle Scholar
  165. 165.
    Ludvigsson J, Wahlberg J. Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old. Ann N Y Acad Sci 2002;958:289–92.PubMedCrossRefGoogle Scholar
  166. 166.
    Stanley HM, Norris JM, Barriga K, Hoffman M, Yu L, Miao D, Erlich HA, Eisenbarth GS, Rewers M. Is presence of islet autoantibodies at birth associated with development of persistent islet autoimmunity? The Diabetes Autoimmunity Study in the Young (DAISY). Diabetes Care 2004;27:497–502.PubMedGoogle Scholar
  167. 167.
    Hamalainen AM, Savola K, Kulmala PK, Koskela P, Akerblom HK, Knip M. Disease-associated autoantibodies during pregnancy and at birth in families affected by type 1 diabetes. Clin Exp Immunol 2001;126:230–5.PubMedGoogle Scholar
  168. 168.
    Rewers M. Islet autoantibodies in cord blood: maternal, fetal, or neither? Diabetes Metab Res Rev 2002;18:2–4.PubMedGoogle Scholar
  169. 169.
    Hamalainen AM, Knip M. Autoimmunity and familial risk of type 1 diabetes. Curr Diab Rep 2002;2:347–53.PubMedGoogle Scholar
  170. 170.
    Achenbach P, Bonifacio E, Koczwara K, Ziegler AG. Natural history of type 1 diabetes. Diabetes 2005;54 Suppl 2:S25–31.PubMedGoogle Scholar
  171. 171.
    Hamalainen AM, Ilonen J, Simell O, Savola K, Kulmala P, Kupila A, Simell T, Erkkola R, Koskela P, Knip M. Prevalence and fate of type 1 diabetes-associated autoantibodies in cord blood samples from newborn infants of non-diabetic mothers. Diabetes Metab Res Rev 2002;18:57–63.PubMedGoogle Scholar
  172. 172.
    Koczwara K, Bonifacio E, Ziegler AG. Transmission of maternal islet antibodies and risk of autoimmune diabetes in offspring of mothers with type 1 diabetes. Diabetes 2004;53:1–4.PubMedGoogle Scholar
  173. 173.
    Warram JH, Krolewski AS, Gottlieb MS, Kahn CR. Differences in risk of T1D in offspring of diabetic mothers and diabetic fathers. N Engl J Med 1984;311:149–52.PubMedCrossRefGoogle Scholar
  174. 174.
    Stene LC, Magnus P, Lie RT, Sovik O, Joner G. Birth weight and childhood onset type 1 diabetes: population based cohort study. BMJ 2001;322:889–92.PubMedGoogle Scholar
  175. 175.
    Dahlquist GG, Pundziute-Lycka A, Nystrom L. Birthweight and risk of type 1 diabetes in children and young adults: a population-based register study. Diabetologia 2005;48:1114–7.PubMedGoogle Scholar
  176. 176.
    Kyvik KO, Bache I, Green A, Beck-Nielsen H, Buschard K. No association between birth weight and Type 1 diabetes mellitus—a twin-control study. Diabet Med 2000;17:158–62.PubMedGoogle Scholar
  177. 177.
    Stene LC, Thorsby PM, Berg JP, Ronningen KS, Undlien DE, Joner G. The relation between size at birth and risk of type 1 diabetes is not influenced by adjustment for the insulin gene (−23 HphI) polymorphism or HLA-DQ genotype. Diabetologia 2006;49:2068–73.PubMedGoogle Scholar
  178. 178.
    Kibirige M, Metcalf B, Renuka R, Wilkin TJ. Testing the accelerator hypothesis: the relationship between body mass and age at diagnosis of T1D. Diabetes Care 2003;26:2865–70.PubMedGoogle Scholar
  179. 179.
    Khan N, Couper JJ. Low-birth-weight infants show earlier onset of IDDM. Diabetes Care 1994;17:653–6.PubMedGoogle Scholar
  180. 180.
    Dabelea D, D’Agostino RB Jr, Mayer-Davis EJ, Pettitt DJ, Imperatore G, Dolan LM, Pihoker C, Hillier TA, Marcovina SM, Linder B, Ruggiero AM, Hamman RF. Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1 (autoimmune) diabetes. Diabetes Care 2006;29:290–4.PubMedGoogle Scholar
  181. 181.
    Larsson HE, Lynch K, Lernmark B, Nilsson A, Hansson G, Almgren P, Lernmark A, Ivarsson SA. Diabetes-associated HLA genotypes affect birthweight in the general population. Diabetologia 2005;48:1484–91.PubMedGoogle Scholar
  182. 182.
    Essex MJ, Klein MH, Cho E, Kalin NH. Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior. Biol Psychiatry 2002;52:776–84.PubMedGoogle Scholar
  183. 183.
    Sepa A, Frodi A, Ludvigsson J. Mothers’ experiences of serious life events increase the risk of diabetes-related autoimmunity in their children. Diabetes Care 2005;28:2394–9.PubMedGoogle Scholar
  184. 184.
    Thernlund GM, Dahlquist G, Hansson K, Ivarsson SA, Ludvigsson J, Sjoblad S, Hagglof B. Psychological stress and the onset of IDDM in children. Diabetes Care 1995;18:1323–9.PubMedGoogle Scholar
  185. 185.
    Sepa A, Frodi A, Ludvigsson J. Could parenting stress and lack of support/confidence function as mediating mechanisms between certain environmental factors and the development of autoimmunity in children?: a study within ABIS. Ann N Y Acad Sci 2002;958:431–5.PubMedCrossRefGoogle Scholar
  186. 186.
    Sepa A, Wahlberg J, Vaarala O, Frodi A, Ludvigsson J. Psychological stress may induce diabetes-related autoimmunity in infancy. Diabetes Care 2005;28:290–5.PubMedGoogle Scholar
  187. 187.
    Vlajinac H, Sipetic S, Marinkovic J, Bjekic M, Kocev N, Sajic S. The Belgrade childhood diabetes study—comparison of children with type 1 diabetes with their siblings. Paediatr Perinat Epidemiol 2006;20:238–43.PubMedGoogle Scholar
  188. 188.
    Zalloua PA, Terwedow H, Shbaklo H, Halaby G, Xu X, Azar ST. Host and environmental factors defining the epidemiology of type 1 diabetes mellitus in a group of Lebanese children and young adults. J Pediatr Endocrinol Metab 2003;16:759–69.PubMedGoogle Scholar
  189. 189.
    Kisch ES. Stressful events and the onset of diabetes mellitus. Isr J Med Sci 1985;21:356–8.PubMedGoogle Scholar
  190. 190.
    Dahlquist G, Blom L, Lönnberg G. The Swedish Childhood Diabetes Study—a multivariate analysis of risk determinants for diabetes in different age groups. Diabetologia 1991;34:757–62.PubMedGoogle Scholar
  191. 191.
    Hagglof B, Blom L, Dahlquist G, Lonnberg G, Sahlin B. The Swedish childhood diabetes study: indications of severe psychological stress as a risk factor for type 1 (insulin-dependent) diabetes mellitus in childhood. Diabetologia 1991;34:579–83.PubMedGoogle Scholar
  192. 192.
    Mosmann TR, Livingstone AM. Dendritic cells: the immune information management experts. Nat Immunol 2004;5:564–6.PubMedGoogle Scholar
  193. 193.
    Kawamura K, Kadowaki N, Kitawaki T, Uchiyama T. Virus-stimulated plasmacytoid dendritic cells induce CD4+cytotoxic regulatory T cells. Blood 2006;107:1031–8.PubMedGoogle Scholar
  194. 194.
    Tang Q, Bluestone JA. Plasmacytoid DCs and T(reg) cells: casual acquaintance or monogamous relationship? Nat Immunol 2006;7:551–3.PubMedGoogle Scholar
  195. 195.
    Nahill SR, Welsh RM. High frequency of cross-reactive cytotoxic T lymphocytes elicited during virus-induced polyclonal cytotoxic T lymphocyte response. J Exp Med 1993;177:317–27.PubMedGoogle Scholar
  196. 196.
    Selin LK, Nahill SR, Welsh RM. Cross-reactivities in memory cytotoxic T lymphocyte recognition of heterologous viruses. J Exp Med 1994;179:1933–43.PubMedGoogle Scholar
  197. 197.
    Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes. Diabetologia 2001;44:914–22.PubMedGoogle Scholar
  198. 198.
    Dahlquist G. Can we slow the rising incidence of childhood-onset autoimmune diabetes? The overload hypothesis. Diabetologia 2006;49:20–4.PubMedGoogle Scholar
  199. 199.
    Gorus FK, Pipeleers DG. Prospects for predicting and stopping the development of type 1 of diabetes. Best Pract Res Clin Endocrinol Metab 2001;15:371–89.PubMedGoogle Scholar
  200. 200.
    Akerblom HK, Reunanen A. The epidemiology of insulin-dependent diabetes mellitus (IDDM) in Finland and in northern Europe. Diabetes Care 1985;8 Suppl 1:10–6.PubMedGoogle Scholar
  201. 201.
    Dahlquist G. The aetiology of type 1 diabetes: an epidemiological perspective. Acta Paediatr Suppl 1998;425:5–10.PubMedGoogle Scholar
  202. 202.
    Baum JD, Ounsted M, Smith MA. Letter: weight gain in infancy and subsequent development of diabetes mellitus in childhood. Lancet 1975;2:866.PubMedGoogle Scholar
  203. 203.
    Baum J, Ounsted M, Smith M. Weight gain in infancy and subsequent development of diabetes mellitus in childhood. Lancet 1975;2:866.PubMedGoogle Scholar
  204. 204.
    Johansson C, Samuelsson U, Ludvigsson J. A high weight gain early in life is associated with an increased risk of type 1 diabetes mellitus. Diabetologia 1994;37:91–4.PubMedGoogle Scholar
  205. 205.
    Hypponen E, Kenward M, Virtanen S, Piitulainen A, Virta-Autio P, Tuomilehto J, Knip M, Akerblom H. Infant feeding, early weight gain, and risk of type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group. Diabetes Care 1999;22:1961–5.PubMedGoogle Scholar
  206. 206.
    Hypponen E, Virtanen SM, Kenward MG, Knip M, Akerblom HK. Obesity, increased linear growth, and risk of type 1 diabetes in children. Diabetes Care 2000;23:1755–60.PubMedGoogle Scholar
  207. 207.
    Ginsberg H. Investigation of insulin sensitivity in treated subjects with ketosis-prone diabetes mellitus. Diabetes 1977;26:278–83.PubMedGoogle Scholar
  208. 208.
    Leslie R, Taylor R, Pozzilli P. The role of insulin resistance in the natural history of type 1 diabetes. Diabet Med 1997;14:327–31.PubMedGoogle Scholar
  209. 209.
    Greenbaum CJ. Insulin resistance in T1D. Diabetes Metab Res Rev 2002;18:192–200.PubMedGoogle Scholar
  210. 210.
    Libman IM, Pietropaolo M, Arslanian SA, LaPorte RE, Becker DJ. Changing prevalence of overweight children and adolescents at onset of T1D. Diabetes Care 2003;26:2871–5.PubMedGoogle Scholar
  211. 211.
    Potau N, Ibanez L, Rique S, Carrascosa A. Pubertal changes in insulin secretion and peripheral insulin sensitivity. Horm Res 1997;48:219–26.PubMedCrossRefGoogle Scholar
  212. 212.
    Moran A, Jacobs DR Jr, Steinberger J, et al. Insulin resistance during puberty: results from clamp studies in 357 children. Diabetes 1999;48:2039–44.PubMedGoogle Scholar
  213. 213.
    Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes 2001;50:2444–50.PubMedGoogle Scholar
  214. 214.
    Guzzaloni G, Grugni G, Mazzilli G, Moro D, Morabito F. Comparison between beta-cell function and insulin resistance indexes in prepubertal and pubertal obese children. Metabolism 2002;51:1011–6.PubMedGoogle Scholar
  215. 215.
    Catalano PM, Tyzbir ED, Roman NM, et al. Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am J Obstet Gynecol 1991;165:1667–72.PubMedGoogle Scholar
  216. 216.
    Buschard K, Buch I, Mølsted-Pedersen L, Hougaard P, Kühl C. Increased incidence of true type 1 diabetes acquired during pregnancy. Br Med J 1987;294:275–9.Google Scholar
  217. 217.
    Fourlanos S, Narendran P, Byrnes GB, Colman PG, Harrison LC. Insulin resistance is a risk factor for progression to type 1 diabetes. Diabetologia 2004;47:1661–7.PubMedGoogle Scholar
  218. 218.
    Blom L, Persson LA, Dahlquist G. A high linear growth is associated with an increased risk of childhood diabetes mellitus. Diabetologia 1992;35:528–33.PubMedGoogle Scholar
  219. 219.
    Bruining GJ. Association between infant growth before onset of juvenile T1D and autoantibodies to IA-2. Netherlands Kolibrie Study Group. Lancet 2000;356:655–6.PubMedGoogle Scholar
  220. 220.
    Rapid early growth is associated with increased risk of childhood type 1 diabetes in various European populations. Diabetes Care 2002;25:1755–60.Google Scholar
  221. 221.
    Lebl J, Schober E, Zidek T, Baldis S, Rami B, Pruhova S, Kolouskova S, Snajderova M, Frisch H. Growth data in large series of 587 children and adolescents with type 1 diabetes mellitus. Endocr Regul 2003;37:153–61.PubMedGoogle Scholar
  222. 222.
    Wilkin TJ, Kibirige M, Mallam K, Renuka R, Metcalf B. Testing the accelerator hypothesis: Type 1 diabetes presents earlier in the fatter child: the EarlyBird Study. Diabetologia 2002;45 (Suppl 2):A 49.Google Scholar
  223. 223.
    Waldhor T, Schober E, Rami B. Regional distribution of risk for childhood diabetes in Austria and possible association with body mass index. Eur J Pediatr 2003;162:380–4.PubMedGoogle Scholar
  224. 224.
    Roep BO, Atkinson M, von Herrath M. Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetes. Nat Rev Immunol 2004;4:989–97.PubMedGoogle Scholar
  225. 225.
    Atkinson MA. ADA Outstanding Scientific Achievement Lecture 2004. Thirty years of investigating the autoimmune basis for type 1 diabetes: why can’t we prevent or reverse this disease? Diabetes 2005;54:1253–63.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Pacific Northwest Research InstituteSeattleUSA
  2. 2.Dept. of MedicineUniv. of WashingtonSeattleUSA

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