Published: Jun 16, 2014
By Crystal Phend, Senior Staff Writer, MedPage Today
Action Points
- Note that this randomized trial in infants at high-risk of developing type 1 diabetes did not demonstrate a benefit to hydrolyzed infant formula compared with traditional cows’ milk-based formula.
- Be aware that the primary outcome, the development of two or more anti-islet antibodies, may not correlate completely with the development of type 1 diabetes; further follow-up of these patients is necessary.
SAN FRANCISCO — For babies at high risk of type 1 diabetes, highly hydrolyzed formula billed as hypoallergenic didn’t help prevent early steps toward the disease, a trial showed.
Appearance of diabetes-associated autoantibodies by age 7 years didn’t differ for babies weaned to casein hydrolysate formula compared with a conventional cows’ milk-based formula, Mikael Knip, MD, PhD, of the University of Helsinki Children’s Hospital, and colleagues found in the TRIGR trial.
Positivity for two or more islet cell autoantibodies was 13.4% among those randomized to the hydrolyzed formula compared with 11.4% in the control group, for an adjusted hazard ratio of 1.23 (95% CI 0.96-1.58).
“Currently, there is no conclusive evidence to revise the dietary recommendations for infants at increased risk for type 1 diabetes,” Knip reported here at the American Diabetes Association meeting and in the June 11 issue of the Journal of the American Medical Association.
The rationale had been that “early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity in children at genetic risk for type 1 diabetes,” and hydrolyzing breaks down those proteins, the group explained.
Their earlier pilot trial had suggested this strategy was working.
With the new evidence, “there is no need to go to these really expensive formulas,” commented Jane Chiang, MD, senior vice president for medical and community affairs at the ADA.
“At this point, none of trials have really shown effective intervention to prevent beta cell destruction,” she told MedPage Today. “Parents feel that it’s somehow their fault or they could do something that somehow controls this, and nothing has substantiated that.”
Longer follow-up of the larger trial until the youngest participant (now age 7) turns at least 10 will be needed to confirm actual progression to a diagnosis of type 1 diabetes, Knip noted.
The presence of more than two islet autoantibodies is associated with a 70% risk developing type 1 diabetes within 10 years.
ADA guidelines updated at the conference didn’t recommend routine screening relatives for type 1 diabetes, despite the 15-fold higher risk in that group, citing lack of clinical interventions to offer. The guidelines didn’t mention choice of infant formula.
The trial included 2,159 infants with an HLA genotype conferring increased risk for type 1 diabetes and a first-degree relative with the disease who were randomized to either an intact cow’s milk formula (plus 20% casein hydrolysate to maintain blinding) or a casein hydrolysate formula after weaning.
Average age at introduction of the assigned formula was about 2 months and continued for a median of 10 to 12 weeks. Breastfeeding to age 6 months was encouraged, but infants were to get the formula for at least the 2 months after weaning.
No adverse events were clinically significantly different between groups, the researchers noted.
The study was supported by Mead Johnson, which provided study formulas without cost, as well as by the NIH, Canadian Institute of Health Research, the EU 5th Framework, Juvenile Diabetes Research Foundation, European Foundation for the Study of Diabetes, Academy of Finland, and Diabetes Fonds.
Knip disclosed relationships with Vactech, Novo Nordisk Pharma, Eli Lilly, Roche Diagnostics, and Valio.
Chiang disclosed no relevant relationships with industry.
Primary source: Journal of the American Medical Association
Source reference: Knip M, et al “Hydrolyzed infant formula and early beta-cell autoimmunity: A randomized clinical trial” JAMA 2014; 311(22): 2279-2287.