The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Cow's milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes
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 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]
Citations
Cites
Insulin antibodies in insulin-dependent diabetics before insulin treatment
Palmer, J. P., Asplin, C. M., Clemons, P., Lyen, K., Tatpati, O., Raghu, P. K., & Paquette, T. L. (1983) · Science · doi:10.1126/science.6362005 · Cited by 1,078
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Are Insulin Autoantibodies Markers for Insulin-Dependent Diabetes Mellitus?
Atkinson, M. A., Maclaren, N. K., Riley, W. J., Winter, W. E., Fisk, D., & Spillar, R. P. (1986) · Diabetes · doi:10.2337/diab.35.8.894 · Cited by 154
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VALUE OF INSULIN AUTOANTIBODIES AS SERUM MARKERS FOR INSULIN-DEPENDENT DIABETES MELLITUS
Wilkin, T. J., Armitage, M., Casey, C. R., Pyke, D. A., Hoskins, P. J., Rodier, M., Diaz, J.-L., & Leslie, R. D. G. (1985) · The Lancet · doi:10.1016/s0140-6736(85)92086-0 · Cited by 128
Karjalainen, J., Knip, M., Mustonen, A., Ilonen, J., & Åkerblom, H. K. (1986) · Diabetes · doi:10.2337/diab.35.5.620 · Cited by 64
Self-citationVaarala, Paronen, Otonkoski, & Åkerblom (1998) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.1998.00282.x · Cited by 61
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Franz, M. J., Bantle, J. P., Beebe, C. A., Brunzell, J. D., Chiasson, J.-L., Garg, A., Holzmeister, L. A., Hoogwerf, B., Mayer-Davis, E., Mooradian, A. D., et al. (2002) · Diabetes Care · doi:10.2337/diacare.25.1.148 · Cited by 1,165
Epidemiology of type 1 diabetes
Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2010.05.011 · Cited by 1,092
Daneman, D. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68341-4 · Cited by 954
Early Infant Feeding and Risk of Developing Type 1 Diabetes–Associated Autoantibodies
Ziegler, A. (2003) · JAMA · doi:10.1001/jama.290.13.1721 · Cited by 562
Fecal Microbiota Composition Differs Between Children With β-Cell Autoimmunity and Those Without
de Goffau, M. C., Luopajärvi, K., Knip, M., Ilonen, J., Ruohtula, T., Härkönen, T., Orivuori, L., Hakala, S., Welling, G. W., Harmsen, H. J. M., et al. (2012) · Diabetes · doi:10.2337/db12-0526 · Cited by 563
Self-citation
Metadata
- 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
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1999-07-01
- Volume
- 48
- Issue
- 7
- Pages
- 1389-1394
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- 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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