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Dietary intervention in infancy may prevent beta-cell autoimmunity
Harland DM. N Engl J Med. 2010;363:1961-1963.
Knip M. N Engl J Med. 2010;363:1900-1908.
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Supplementing breast milk with casein hydrolysate formula appears to have a long-lasting, positive effect on beta-cell autoimmunity markers that lead to type 1 diabetes.
“A short duration of breast-feeding and early exposure to complex dietary proteins have been implicated as risk factors for advanced beta-cell autoimmunity or clinical type 1 diabetes,” researchers wrote. “Early nutritional intervention may help to prevent type 1 diabetes and has been reported to be successful in experimental models of autoimmune disease.”
To investigate this potential relationship, researchers for the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) enrolled 230 infants at 15 hospitals in Finland between 1995 and 1997. All had susceptibility to type 1 diabetes via certain human leukocyte antigen genotypes and had at least one family member with the disease. One hundred thirteen infants were randomly assigned to receive casein hydrolysate formula and 117 to receive a cow’s milk-based formula whenever breast milk was unavailable during the first 6 to 8 months of life.
Appearance of autoantibodies
Age at formula introduction differed between the two groups, with the control group experiencing introduction at a median age of 1.1 months vs. 2.6 months in the casein hydrolysate formula group (P=.03). The median duration of formula feeding was also shorter in the casein hydrolysate formula group (3.3 months) compared with infants in the control group (4.9 months; P=.05).
During a median follow-up of 10 years, autoantibodies were detected significantly less often among children fed with casein hydrolysate formula, with only 17% of children in this group experiencing development of at least one autoantibody compared with 30% in the control group. Further, 8% of children fed casein hydrolysate formula tested positive for at least two autoantibodies compared with 16% in the control arm.
Unadjusted analyses revealed that the HR for having at least one autoantibody in the casein hydrolysate group compared with the control group was 0.54 (95% CI, 0.29-0.95), according to the researchers. After adjustment for duration of formula feeding, the HR dropped slightly to 0.51 (95% CI, 0.28-0.91).
Similarly, the unadjusted HR for development of at least two autoantibodies was 0.52 (95% CI, 0.21-1.17), and the adjusted HR was 0.47 (95% CI, 0.19-1.07).
Development of diabetes
Progression to type 1 diabetes was comparable between the two study arms, the researchers said, with 6% of children in the casein hydrolysate formula group and 8% of children in the control group developing the disease by 10 years of age.
Data did not indicate a significant association between the feeding intervention and risk for type 1 diabetes (HR=0.8; 95% CI, 0.3-2.14). After adjustment for duration of formula exposure, the HR was 0.48 (95% CI, 0.14-1.61).
“Although it seems likely that dietary constituents, not too surprisingly, can influence the immune system and intermediary metabolism, our knowledge of the mechanisms at play are, at present, rudimentary,” David M. Harlan, MD, and Mary M. Lee, MD, of the University of Massachusetts School of Medicine in Worcester, wrote in an accompanying editorial. “Data from the ongoing multicenter [TRIGR study] should help clarify whether hydrolyzed casein formula exerts a protective effect against the risk of type 1 diabetes.”
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