Is Type 1 Diabetes a Disease of the Gut Immune System Triggered by Cow’s Milk Insulin?

  • Outi Vaarala
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 569)


The role of the gut immune system in the development of autoimmune m type 1 diabetes is evaluated in this review with special emphasis in the hypothesis suggesting that dietary cow’s milk insulin could trigger betacell autoimmunity when the mechanisms of oral tolerance are disturbed.

Key words

type 1 diabetes insulin gut beta-cell autoimmunity alpha4beta7-integrin cytokines breast milk microflora enterovirus 


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  1. Blanas E, Carbone FR, Allison J, Miller JFAP, Heath WR, 1996, Induction of autoimmune diabetes by oral administration of autoantigen. Science 274: 1707–1709.CrossRefPubMedGoogle Scholar
  2. Elliott RB, Reddy SN, Bibby NJ, Kida K, 1998, Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia 31: 62–4.Google Scholar
  3. Gerstein HC, 1994, Cow’s milk exposure and type I diabetes mellitus. A critical overview of the clinical literature. Diabetes Care 17: 13–9.PubMedGoogle Scholar
  4. Hanninen A, Salmi M, Simell O, Jalkanen S, 1996, Mucosa-associated (beta7-integrinhigh) lymphocytes accumulate early in the pancreas of NOD mice and show aberrant recirculation behavior. Diabetes 45: 1173–1180.PubMedGoogle Scholar
  5. Hanninen A, Jaakkola I, Jalkanen S, 1998, Mucosal addressin is required for the development of diabetes in nonobese diabetic mice. J Immunol 160: 6018–6025.PubMedGoogle Scholar
  6. Hanninen A, Salmi M, Simell O, Jalkanen S, 1993,. Endothelial cell-binding properties of lymphocytes infiltrated into human diabetic pancreas. Implications for pathogenesis of IDDM. Diabetes 42: 1556–1562.Google Scholar
  7. Kimpimaki T, Erkkola M, Korhonen S, Kupila A, Virtanen SM, Ilonen J, Simell O, Knip M, 2001, Short-term exclusive breastfeeding predisposes young children with increased genetic risk of Type I diabetes to progressive beta-cell autoimmunity. Diabetologia 44: 63–9.PubMedGoogle Scholar
  8. Norris JM, Barriga K, Klingensmith G, Hoffman M, Eisenbarth GS, Erlich HA, Rewers M, 2003, Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 290:1713–1720.CrossRefPubMedGoogle Scholar
  9. Paronen J, Klemetti P, Kantele JM, Savilahti E, Perheentupa J, Akerblom HK, Vaarala O, 1997, Glutamate decarboxylase-reactive peripheral blood lymphocytes from patients with IDDM express gut-specific homing receptor alpha4beta7-integrin. Diabetes 46: 583–8.PubMedGoogle Scholar
  10. Paronen J, Knip M, Savilahti E, Virtanen SM, Ilonen J, Akerblom HK, Vaarala O, 2000, Effect of cow’s milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish Trial to Reduce IDDM in the Genetically at Risk Study Group. Diabetes 49: 1657–65.PubMedGoogle Scholar
  11. Scott FW, Cloutier HE, Kleemann R, Woerz-Pagenstert U, Rowsell P, Modler HW, Kolb H, 1997, Potential mechanisms by which certain foods promote or inhibit the development of spontaneous diabetes in BB rats: dose, timing, early effect on islet area, and switch in infiltrate from Th1 to Th2 cells. Diabetes 46: 589–98.PubMedGoogle Scholar
  12. Vaarala O, Knip M, Paronen J, Hämäläinen A-M, Muona P, Väätäinen M, Ilonen J, Simell O, Åkerblom HK, 1999, Cow’s milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes. Diabetes 48: 1389–1394.PubMedGoogle Scholar
  13. Vaarala O, 2002a, Gut immune system and type 1 diabetes. Ann N Y Acad Sci 958: 39–46PubMedGoogle Scholar
  14. Vaarala O, Klemetti P, Juhela S, Simell O, Hyöty H, Ilonen J, 2002b,The effect of coincident enterovirus infection and cow’s milk exposure on immunization to insulin in early infancy. Diabetologia 45: 531–534.CrossRefPubMedGoogle Scholar
  15. Verge CF, Howard NJ, Irwig L, Simpson JM, Mackerras D, Silink M, 1994, Environmental factors in childhood IDDM. A population-based, case-control study. Diabetes Care 17: 1381–9.PubMedGoogle Scholar
  16. Westerholm-Ormio M, Vaarala O, Pihkanen P, Ilonen J, Savilahti E, 2003, Immunologic activity in the small intestinal mucosa of pediatric patients with type 1 diabetes. Diabetes 52: 2287–2295.PubMedGoogle Scholar
  17. Virtanen SM, Laara E, Hypponen E, Reijonen H, Rasanen L, Aro A, Knip M, Ilonen J, Akerblom HK, 2000, Cow’s milk consumption, HLA-DQB1 genotypeiabetes. Childhood, and type 1 diabetes: a nested case-control study of siblings of children with d diabetes in Finland study group. Diabetes 49: 912–7.PubMedGoogle Scholar
  18. Ziegler AG, Schmid S, Huber D, Hummel M, Bonifacio E, 2003, Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA 290:1721–1728.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Outi Vaarala
    • 1
  1. 1.Department of Molecular and Clinical Medicine, Faculty of Health SciencesUniversity of LinköpingSweden

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