title: Short-term exclusive breastfeeding predisposes young children with increased genetic risk of Type I diabetes to progressive beta-cell autoimmunity.
abstract: OBJECTIVE
  This study aimed to establish the relation between early infant nutrition and signs of beta-cell autoimmunity in young children.
  
  
  METHODS
  We identified and observed from birth 2949 infants with increased genetic risk of Type I (insulin-dependent) diabetes mellitus (HLA DQB1*02/ *0302 or DQB1*0302/x, x = other than *02, *0301 or *0602) and monitored them for islet cell antibodies at 3 to 6 month intervals. If an infant seroconverted to islet cell antibody positivity, all of his or her samples were also analysed for autoantibodies to insulin, GAD65 (GADA) and to the protein tyrosine phosphatase related IA-2 molecule (IA-2A). Our case-control study comprises the first 65 children who seroconverted to islet cell antibody positivity before the age of 4 years and 390 control children who were islet cell antibody-negative (six control children/ case). We monitored the duration of exclusive and total breastfeeding and the age at which cows' milk was introduced.
  
  
  RESULTS
  Infants who had been breastfed exclusively for at least 4 months had lower risk of seroconversion to positivity for IA-2A or all four autoantibodies [odds ratio (OR) 0.24; 95 % CI 0.06-0.94 and OR 0.17; 95 % CI 0.03-0.86, respectively] than those infants who had been breastfed exclusively for less than 2 months. The risk of seroconversion to positivity for IA-2A or all four autoantibodies was higher in those younger than 2 months (OR 4.37; 95 % CI 1.33-14.42 and OR 5.02; 95 % CI 1.27-19.89) or aged 2 to 3.9 months (OR 5.50; 95 % CI 1.21-25.04 and 6.19; 95% CI 1.10-34.84) when they first received cows' milk than in those aged 4 months or older.
  
  
  CONCLUSIONS
  These observations suggest that short-term breastfeeding and the early introduction of cows' milk-based infant formula predispose young children who are genetically susceptible to Type I diabetes to progressive signs of beta-cell autoimmunity.
authors.affiliation: Department of Pediatrics, Tampere University Hospital, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Kimpimäki
authors.forename: M
authors.initials: M
authors.lastname: Erkkola
authors.forename: S
authors.initials: S
authors.lastname: Korhonen
authors.forename: A
authors.initials: A
authors.lastname: Kupila
authors.forename: S M
authors.initials: SM
authors.lastname: Virtanen
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
authors.forename: O
authors.initials: O
authors.lastname: Simell
authors.forename: M
authors.initials: M
authors.lastname: Knip
mesh_terms: D000375:Aging; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D001942:Breast Feeding; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D007223:Infant; D007225:Infant Food; D007227:Infant Nutritional Physiological Phenomena; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008892:Milk; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; C096322:ICA512 autoantibody; D007328:Insulin; D005968:Glutamate Decarboxylase