First Infant Formula Type and Risk of Islet Autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) Study

Sandra Hummel¹, Andreas Beyerlein², Roy Tamura³, Ulla Uusitalo³, Carin Andrén Aronsson⁴, Jimin Yang³, Anne Riikonen⁵, Åke Lernmark⁴, Marian J Rewers⁶, William A Hagopian⁷, Jin-Xiong She⁸, Olli G Simell⁹, Jorma Toppari^{9

10}, Anette-G Ziegler², Beena Akolkar¹¹, Jeffrey P Krischer³, Suvi M Virtanen^{5

12}, Jill M Norris¹³; TEDDY Study Group

Affiliations

¹ Institute of Diabetes Research, Helmholtz Zentrum München, Munich, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Forschergruppe Diabetes e.V., Neuherberg, Germany sandra.hummel@lrz.uni-muenchen.de.
² Institute of Diabetes Research, Helmholtz Zentrum München, Munich, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Forschergruppe Diabetes e.V., Neuherberg, Germany.
³ Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL.
⁴ Department of Clinical Sciences, Lund University/Clinical Research Centre, Skåne University Hospital (SUS), Malmö, Sweden.
⁵ Unit of Nutrition, National Institute for Health and Welfare, Helsinki, and Faculty of Social Sciences, University of Tampere, Tampere, Finland.
⁶ Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO.
⁷ Pacific Northwest Diabetes Research Institute, Seattle, WA.
⁸ Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA.
⁹ Department of Pediatrics, Turku University Hospital, Turku, Finland.
¹⁰ Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
¹¹ National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
¹² Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, and The Science Center of Pirkanmaa Hospital District, Tampere, Finland.
¹³ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO.

PMID: 28096222
PMCID: PMC5319477
DOI: 10.2337/dc16-1624

First Infant Formula Type and Risk of Islet Autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) Study

Sandra Hummel et al. Diabetes Care. 2017 Mar.

. 2017 Mar;40(3):398-404.

doi: 10.2337/dc16-1624. Epub 2017 Jan 17.

Authors

Affiliations

¹ Institute of Diabetes Research, Helmholtz Zentrum München, Munich, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Forschergruppe Diabetes e.V., Neuherberg, Germany sandra.hummel@lrz.uni-muenchen.de.
² Institute of Diabetes Research, Helmholtz Zentrum München, Munich, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Forschergruppe Diabetes e.V., Neuherberg, Germany.
³ Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL.
⁴ Department of Clinical Sciences, Lund University/Clinical Research Centre, Skåne University Hospital (SUS), Malmö, Sweden.
⁵ Unit of Nutrition, National Institute for Health and Welfare, Helsinki, and Faculty of Social Sciences, University of Tampere, Tampere, Finland.
⁶ Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO.
⁷ Pacific Northwest Diabetes Research Institute, Seattle, WA.
⁸ Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA.
⁹ Department of Pediatrics, Turku University Hospital, Turku, Finland.
¹⁰ Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
¹¹ National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
¹² Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, and The Science Center of Pirkanmaa Hospital District, Tampere, Finland.
¹³ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO.

PMID: 28096222
PMCID: PMC5319477
DOI: 10.2337/dc16-1624

Abstract

Objective: Studies on the introduction of infant formulas and its effect on the risk of islet autoimmunity and type 1 diabetes (T1D) have yielded inconsistent results. We investigated whether the introduction of formula based on hydrolyzed cow's milk as the first formula is associated with reduced islet autoimmunity risk in a large prospective cohort.

Research design and methods: The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively monitors 8,676 children at increased genetic risk for T1D. Autoantibodies to insulin, GAD65, and IA2 were measured regularly to define islet autoimmunity. Information on formula feeding was collected by questionnaires at 3 months of age.

Results: In survival analyses, after adjustment for family history with T1D, HLA genotype, sex, country, delivery mode, breast-feeding ≥3 months, and seasonality of birth, we observed no significant association with islet autoimmunity in infants who received extensively hydrolyzed compared with nonhydrolyzed cow's milk-based formula as the first formula during the first 3 months (adjusted hazard ratio 1.38 [95% CI 0.95; 2.01]), and a significantly increased risk for extensively hydrolyzed formula introduced during the first 7 days (adjusted hazard ratio 1.57 [1.04; 2.38]). Using a partially hydrolyzed or other formula as the first formula, or no formula, was not associated with islet autoimmunity risk.

Conclusions: These results add to the existing evidence that islet autoimmunity risk is not reduced, and may be increased, by using hydrolyzed compared with nonhydrolyzed cow's milk-based infant formula as the first formula in infants at increased genetic risk for T1D.

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Figures

**Figure 1**
Cumulative risk of any islet autoimmunity with respect to type of first formula introduced during the first 3 months (A) and 7 days (B). The P values refer to log-rank tests. The numbers below the graphs indicate the number of subjects in each formula group at each follow-up.

See this image and copyright information in PMC

References

1. World Health Organization. Infant and young child feeding data by country, 2016. Available from http://www.who.int/nutrition/databases/infantfeeding/countries/en/. Accessed 28 April 2016
1. Gerstein HC. Cow’s milk exposure and type I diabetes mellitus. A critical overview of the clinical literature. Diabetes Care 1994;17:13–19 - PubMed
1. Norris JM, Scott FW. A meta-analysis of infant diet and insulin-dependent diabetes mellitus: do biases play a role? Epidemiology 1996;7:87–92 - PubMed
1. Virtanen SM, Kenward MG, Erkkola M, et al. . Age at introduction of new foods and advanced beta cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes. Diabetologia 2006;49:1512–1521 - PubMed
1. Chmiel R, Beyerlein A, Knopff A, Hummel S, Ziegler AG, Winkler C. Early infant feeding and risk of developing islet autoimmunity and type 1 diabetes. Acta Diabetol 2015;52:621–624 - PubMed

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First Infant Formula Type and Risk of Islet Autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) Study

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First Infant Formula Type and Risk of Islet Autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) Study

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