Dietary intervention in infancy and later signs of beta-cell autoimmunity.
BACKGROUND
Early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity and type 1 diabetes in children with genetic susceptibility. We tested the hypothesis that supplementing breast milk with highly hydrolyzed milk formula would decrease the cumulative incidence of diabetes-associated autoantibodies in such children.


METHODS
In this double-blind, randomized trial, we assigned 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes to receive either a casein hydrolysate formula or a conventional, cow's-milk-based formula (control) whenever breast milk was not available during the first 6 to 8 months of life. Autoantibodies to insulin, glutamic acid decarboxylase (GAD), the insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 were analyzed with the use of radiobinding assays, and islet-cell antibodies were analyzed with the use of immunofluorescence, during a median observation period of 10 years (mean, 7.5). The children were monitored for incident type 1 diabetes until they were 10 years of age.


RESULTS
The unadjusted hazard ratio for positivity for one or more autoantibodies in the casein hydrolysate group, as compared with the control group, was 0.54 (95% confidence interval [CI], 0.29 to 0.95), and the hazard ratio adjusted for an observed difference in the duration of exposure to the study formula was 0.51 (95% CI, 0.28 to 0.91). The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 (95% CI, 0.21 to 1.17), and the adjusted hazard ratio was 0.47 (95% CI, 0.19 to 1.07). The rate of reported adverse events was similar in the two groups.


CONCLUSIONS
Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity--markers that may reflect an autoimmune process leading to type 1 diabetes. (ClinicalTrials.gov number, NCT00570102.).
Hospital for Children and Adolescents, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. mikael.knip@helsinki.fi
Mikael
M
Knip
Suvi M
SM
Virtanen
Karri
K
Seppä
Jorma
J
Ilonen
Erkki
E
Savilahti
Outi
O
Vaarala
Antti
A
Reunanen
Kari
K
Teramo
Anu-Maaria
AM
Hämäläinen
Johanna
J
Paronen
Hans-Michael
HM
Dosch
Timo
T
Hakulinen
Hans K
HK
Akerblom
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood; D002364:Caseins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000517:prevention & control*; D018450:Disease Progression; D004311:Double-Blind Method; D020022:Genetic Predisposition to Disease; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007231:Infant, Newborn; D050417:Insulin-Secreting Cells / Q000276:immunology*; D008892:Milk / Q000276:immunology; D008895:Milk, Human; D010865:Pilot Projects
D001323:Autoantibodies; D015415:Biomarkers; D002364:Caseins; C475729:casein hydrolysate