Type 1 diabetes (T1D) is a life-changing diagnosis for affected children and their families. Since prevention is always better than treatment, and prevention requires an understanding of pathobiology, what do we know about the etiology of T1D?
We know that T1D likely reflects the actions of both genetic and environmental factors. Concordance for T1D among identical twins is roughly 50%, suggesting that genetics play a significant role in disease development but are not the whole story. The role of diet has been an obvious consideration as an environmental factor that may influence the development of T1D. For instance, some studies have hinted that exposure to complex dietary proteins in early infancy may increase the risk of developing T1D later in life.
This week in NEJM, Knip et al. report from the results of a randomized, double blind study of newborn infants with a first-degree relative with T1D. These infants are at high risk of developing T1D. The study, conducted at 15 Finnish hospitals, observed 208 infants for a median follow-up time of 10 years. The authors tracked beta cell-specific autoantibody seroconversion among infants receiving an extensively hydrolyzed casein-based “intervention” formula – a sort of predigested milk – as compared with infants receiving a “control” formula. In both groups, the formula was used at the mothers’ discretion to supplement breastfeeding.
Knip et al. found that 17% of infants receiving the intervention formula developed at least one of the autoantibodies studied, as compared with 30% of the infants who received the control formula. This difference was statistically significant even after adjusting for duration of study formula exposure and age at formula introduction. However, no statistically significant difference was observed between the two groups for the number of study participants ultimately developing overt T1D (6.2% of infants in the intervention arm, as compared with 7.7% of infants in the control arm).
In an accompanying editorial, Drs. David Harlan and Mary Lee of the University of Massachusetts School of Medicine point out that confounding factors such as the quantity of formula ingested may have contributed to the observed difference in seroconversion between the two groups. They write, “confidence in the observation might be increased had the timing of autoantibody appearance, the ultimate autoantibody titer, or the secondary outcome of T1D diagnosis differed between the groups, but these did not.”
Nevertheless, this study suggests that there may be value in preventive dietary intervention as a strategy to reduce the risk of developing T1D. Potential mechanisms of risk reduction that have been proposed based on animal studies include decreased gut permeability, induction of regulatory T cells to keep the cellular immune response in check, and favorable changes in gut microflora. Future investigation of these mechanisms may help to elucidate how T1D develops and may suggest a strategy for early dietary intervention.
What dietary or other preventive measures do you currently recommend for infants at risk for developing T1D? Will the findings of this study influence your recommendations?