The effect of childhood cow's milk intake and HLA-DR genotype on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young

Pediatr Diabetes. 2015 Feb;16(1):31-8. doi: 10.1111/pedi.12115. Epub 2014 Jan 20.


Background: Cow's milk intake has been inconsistently associated with islet autoimmunity (IA) and type 1 diabetes (T1D) development. Genetic and environmental factors may modify the effect of cow's milk on IA and T1D risk.

Methods: The Diabetes Autoimmunity Study in the Young (DAISY) follows children at increased T1D risk of IA (presence of autoantibodies to insulin, GAD65, or IA-2 twice in succession) and T1D development. We examined 1835 DAISY children with data on cow's milk intake: 143 developed IA, 40 subsequently developed T1D. Cow's milk protein and lactose intake were calculated from prospectively collected parent- and self-reported food frequency questionnaires (FFQ). High risk HLA-DR genotype: HLA-DR3/4,DQB1*0302; low/moderate risk: all other genotypes. We examined interactions between cow's milk intake, age at cow's milk introduction, and HLA-DR genotype in IA and T1D development. Interaction models contained the base terms (e.g., cow's milk protein and HLA-DR genotype) and an interaction term (e.g., cow's milk protein*HLA-DR genotype).

Results: In survival models adjusted for total calories, FFQ type, T1D family history, and ethnicity, greater cow's milk protein intake was associated with increased IA risk in children with low/moderate risk HLA-DR genotypes [hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.08-1.84], but not in children with high risk HLA-DR genotypes. Cow's milk protein intake was associated with progression to T1D (HR: 1.59, CI: 1.13-2.25) in children with IA.

Conclusions: Greater cow's milk intake may increase risk of IA and progression to T1D. Early in the T1D disease process, cow's milk intake may be more influential in children with low/moderate genetic T1D risk.

Keywords: HLA-DR genotype; IA; childhood diet; cow's milk protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoimmunity*
  • Cattle
  • Child
  • Child Nutritional Physiological Phenomena*
  • Child, Preschool
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Disease Susceptibility
  • Eating / physiology*
  • Female
  • Genotype
  • HLA-DR Antigens / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Islets of Langerhans / immunology*
  • Male
  • Milk*
  • Risk Factors
  • Surveys and Questionnaires


  • HLA-DR Antigens