Effect of coincident enterovirus infection and cows' milk exposure on immunisation to insulin in early infancy

Diabetologia. 2002 Apr;45(4):531-4. doi: 10.1007/s00125-002-0787-8.


Aims/hypothesis: Insulin autoantibodies appear often as the first autoantibody in children who develop islet-cell autoimmunity. Our recent studies indicate that primary immunisation to insulin is induced in early infancy by exposure to dietary bovine insulin present in cows' milk formulas. As gut-associated lymphoid tissue is also the primary replication site of enteroviruses, we tested whether enterovirus infections could modify the development of immune response to dietary insulin in early infancy.

Methods: We studied the development of IgG-antibodies to dietary bovine insulin by enzyme immunoassay in relation to enteroviral infections determined by T-cell proliferation response to the Coxsackie B4 virus and by serological tests for enterovirus antigens in 57 infants who carried the HLA DQB1(*)02/0302 diabetes risk genotype and participated in a Finnish population-based birth-cohort study (Diabetes Prediction and Prevention Project, DIPP, study).

Results: In the infants exposed to cows' milk formulas before the age of 3 months, those who had a T-cell proliferation response to enterovirus antigen at 3 months of age ( n = 12) had higher concentrations of IgG-antibodies to bovine insulin at the age of 6 and 9 months than those who did not have T-cell proliferation response to enterovirus antigen ( n = 25) (median OD were 0.742 vs 0.427, p = 0.04, and 0.477 vs 0.293, p = 0.02, respectively).

Conclusion/interpretation: Our results suggest that two epidemiological risk factors of Type I (insulin-dependent) diabetes mellitus, enterovirus infections and exposure to cows' milk formulas, could modify the immunisation to insulin in early infancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Cattle
  • Cohort Studies
  • Enterovirus B, Human / immunology*
  • Enterovirus Infections / immunology*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / blood
  • Infant
  • Infant Food
  • Insulin Antibodies / immunology*
  • Lymphocyte Activation
  • Milk / immunology*
  • T-Lymphocytes / immunology*


  • Autoantibodies
  • Immunoglobulin G
  • Insulin Antibodies