According to pilot studies, exposure to complex dietary proteins early in life may increase the risk of beta cell autoimmunity in children who are at risk for type 1 diabetes….
Several autoantibodies are said to predict clinical type 1 diabetes including islet cell antibodies (ICA), insulin autoantibodies, autoantibodies to glutamic acid decarboxylase (GAD) and the tyrosine phosphatase-related insulinoma associated 2 molecule (IA-2). From previous studies it has been shown that those positive for 2 or more autoantibodies have around a 60% chance for developing diabetes over 10 years, whereas the risk for those with a single autoantibody is about 15% and drops to less than 1% with no identifiable autoantibodies.
Increasing evidence tells us that beta cell autoimmunity emerges early in life. Due to this any measures aimed at prevention of type 1 diabetes must start early in life. Prior studies have indicated that weaning an infant to an extensively hydrolyzed casein formula decreased the incidence of autoantibodies that are associated with type 1 diabetes in those children with a first degree relative afflicted with the disease and a risk associated HLA genotype. This led to the study known as the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) which is aimed at assessing intervention in the development of type 1 diabetes prior to age 10.
A randomized, double-blind study of 2159 participants was conducted in 78 centers throughout 15 countries. Newborns with a first-degree relative with type 1 diabetes were recruited between May 2002 and January 2007. These infants were observed until April 16, 2013. A total of 1,078 infants were chosen to be weaned to the extensively hydrolyzed casein formula while 1,081 were weaned to conventional formula that was composed of 80% intact cow’s milk protein and 20% hydrolyzed casein. The dietary intervention period lasted until the infant was at least 6 months of age but no older than 8 months of age. The participant had to have at least 60 consecutive days of study formula with the mean intervention time being 10.2 weeks in the experimental group and 11.7 weeks in the control group. Parents were asked not to feed the infants any foods containing bovine protein during the time they received the study formula. The primary outcome of the study was presentation of type 1 diabetes by age 10 while positivity for 2 or more islet autoantibodies by age 6 was a secondary outcome.
Cord blood samples and follow-up blood samples were taken from participants at 3, 6, 9, 12, 18 and 24 months of age and then once a year until age 10. The cord blood was used for HLA genotyping to screen for DQB1 and DQA1 alleles.
Analysis showed that 13.4% of children in the experimental group tested positive for 2 or more autoantibodies as compared with 11.3% of the control group. The unadjusted hazard ratio was for positivity for at least 2 autoantibodies was 1.21 for those randomized to be weaned to the casein hydrolysate while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23. At least 1 autoantibody developed in 41.6% and 40.0% in the experimental and control groups, respectively. The earliest age of detection of autoantibodies was 3 months and the latest was at age 9. For the children who tested positive for autoantibodies there was no difference in the initial or maximum autoantibody titers between the two groups. There were also no differences in the rate of adverse events reported for the 2 groups.
Contrary to what initial studies lead researches to believe, the TRIGR study showed that weaning to a highly hydrolyzed formula during infancy was not associated with any reduction in beta cell autoimmunity and would therefore not be beneficial in the prevention of type 1 diabetes.
- Prior studies have reported that several autoantibodies can predict clinical type 1 diabetes.
- It has been shown that those positive for 2 or more autoantibodies have around a 60% chance for developing diabetes over 10 years, whereas the risk for those with a single autoantibody is about 15% and drops to less than 1% with no identifiable autoantibodies.
- The TRIGR study showed that weaning to a highly hydrolyzed formula during infancy was not associated with any reduction in beta cell autoimmunity and would therefore not be beneficial in the prevention of type 1 diabetes.
Knip, Mikael MD, Akerblom, Hans MD, Becker, Dorothy MD, et al. Hydrolyzed Infant Formula and Early Beta-Cell Autoimmunity: A Randomized Clinical Trial. JAMA. 2014; 311(22): 2279-2287. http://jama.jamanetwork.com.cuhsl.creighton.edu/article.aspx?articleid=1878718.