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Cited by 182Diabetes and associated disordersInfant Nutrition and HealthDiabetes Management and Research

Cow's milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes

Vaarala, O, Knip, M, Paronen, J, Hämäläinen, A M, Muona, P, Väätäinen, M, Ilonen, J, Simell, O +1 more·1999·Diabetes
DOI 10.2337/diabetes.48.7.1389
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Abstract

Insulin autoantibodies (IAAs) often appear as the first sign of islet cell autoimmunity in prediabetic children. Because cow's milk contains bovine insulin, we followed the development of insulin-binding antibodies in children fed with cow's milk formula. Bovine insulin- and human insulin-binding antibodies by enzyme immunoassay and IAA by radioimmunoassay were analyzed in 200 infants carrying HLA-DQB1*0302 but no protective alleles who participated in a Finnish population-based birth-cohort study. Based on the prospectively registered information, the first 100 infants enrolled in the study who were exposed to cow's milk formula before age 12 weeks and the first 100 infants enrolled in the study who were exclusively breast-fed for longer than their first 12 weeks of life were selected for the present study. Also, 11 children from the birth cohort who developed at least two diabetes-associated autoantibodies, 98 children with newly diagnosed type 1 diabetes, and 92 healthy children were studied. We found that the amount of IgG-antibodies binding to bovine insulin was higher at age 3 months in infants who were exposed to cow's milk formula than in infants who were exclusively breast-fed at that age (median 0.521 vs. 0.190; P < 0.0001). The antibodies binding to bovine insulin cross-reacted with human insulin. None of these infants tested positive for IAA. The levels of bovine insulin-binding antibodies declined in both groups at ages 12 and 18 months, whereas in the 11 children with at least two diabetes-associated autoantibodies the levels increased during the follow-up period (P < 0.0001). IgG antibodies correlated with IgG2 antibodies binding to bovine insulin (r = 0.43, P = 0.004) and IAA (r = 0.27, P = 0.02) in diabetic children, but not in healthy children. Cow's milk feeding is an environmental trigger of immunity to insulin in infancy that may explain the epidemiological link between the risk of type 1 diabetes and early exposure to cow's milk formulas. This immune response to insulin may later be diverted into autoaggressive immunity against beta-cells in some individuals, as indicated by our findings in children with diabetes-associated autoantibodies.

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  • Evidence on whether early introduction of cow's milk or protective effects of breast milk contribute to childhood type 1 diabetes is equivocal and may depend on genetic susceptibility.

    “Evidence regarding early introduction of cow’s milk (or protective effects of breast milk consumption) in infants contributing to the development of childhood T1D is equivocal73–76 and may depend on genetic susceptibility77.”

    From Epidemiology of type 1 diabetes (2010) · cites this paper as [76]

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Authors
Vaarala, O., Knip, M., Paronen, J., Hämäläinen, A. M., Muona, P., Väätäinen, M., Ilonen, J., Simell, O., & Akerblom, H. K.
Affiliations
Department of Biochemistry, National Public Health Institute, Helsinki, Finland. outi.vaarala@ktl.fi
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
1999-07-01
Volume
48
Issue
7
Pages
1389-1394
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.48.7.1389
OpenAlex
W2161412046
Cited by
182
References
9
Citations by year
2026: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 9 · 2018: 4 · 2017: 9 · 2016: 7 · 2015: 4 · 2014: 8 · 2013: 13 · 2012: 10
FWCI
3.71
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
cow's milk formula, type 1 diabetes, insulin autoantibodies, bovine insulin, HLA-DQB1*0302, islet autoimmunity, infant feeding, breastfeeding, IgG2 antibodies, environmental triggers of autoimmunity
MeSH terms
Antigen-Antibody Reactions, Autoantibodies, Diabetes Mellitus, Type 1, Finland, Humans, Immunoglobulin G, Immunization, Infant, Infant Food, Infant, Newborn, Insulin, Prospective Studies, Risk Factors, Genetic Predisposition to Disease

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