MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In a large population of pregnant women, we found that the risk of the offspring being diagnosed with type 1 diabetes before the age of 15.6 years (the follow up period) was doubled in the group of women ingesting the highest amounts of gluten (20-66 g/day) versus the group of women ingesting the lowest amounts of gluten (0-7 g/day). For every additional 10 grams of gluten ingested, the risk for type 1 diabetes in the child increased by a factor of 1.31.
It the sense that it was a hypothesis that we specifically tested, we were not surprised. We had seen in animal experiments that a gluten-free diet during pregnancy protected the offspring from diabetes, and we wanted to see if we could prove the same pattern in humans. There could be many reasons why we would not be able to show the association, even if it was there (sample size, low quality data, covariates we could not correct for and so on), but we were off course pleasantly surprised that we found the association that we were looking for, in particular because it is quite robust
MedicalResearch.com: What should readers take away from your report?
Response: We currently do not recommend pregnant women to change their diet to gluten free. This is because the study is observational and the link that we describe is an association. The study design does not allow for conclusions to be drawn on causality. Just like there are more childbirths and more storks in the spring, it does not mean that the storks are bringing the newborns. So, in order to show that gluten is really the reason for more diabetes in the children, we would have to set up (ideally) a double-blind, prospective, randomised study, which would of course be impossible, since the number of participants would have to be very large (as the diabetes risk i only around 1% in the Danish population). So a statistical study is the best we can do right now, but as a minimum, we would like to see the results replicated in other populations than the Danish.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The study brings new ideas to how type 1 diabetes develops. We did not know that the pregnancy period is that important for the development of the disease – that the development of it is starting that early in life – and it also holds the potential to reduction in the frequency of the disease by simply changing the diet during pregnancy. As mentioned, it should be examined in more detail what other consequences a gluten-free diet might have on other diseases as well as on the mothers health. We don’t know if gluten in fact protects agains other diseases and if the removal of it from the mother’s diet might provoke a higher occurrence of other diseases.
MedicalResearch.com: Is there anything else you would like to add?
Response: Type 1 diabetes is a serious disease that, in spite of optimal treatment, shortens the life by approximately ten years, and much more than that if diagnosed at young age (<10 years). It is therefore of great value to be able to prevent the disease. However, the treatment must be safe, as insulin treatment, how tedious it might be, allows the patients to live for many years. Gluten-free diet could be one such treatment, either during pregnancy or postnatally, but it remains to be proven that such treatment can actually prevent diabetes development in a safe way.
We currently do not know how gluten influences type 1 diabetes. Gluten is a molecule that is hard to dissolve, it is in fact defined by the elastic network that remains when you have washed away everything else in a handful of white flour. However, in order to digest any protein, including gluten, it must be in solution. Gluten is soluble in hydrochloric acid, so it is probably in solution in the ventricle, but the pH rises in the duodenum, and gluten probably precipitates again. That makes it hard to digest by the pancreatic enzymes, and fragments probably remain. We have seen in animal experiments that such fragments can still be absorbed (we investigated a 33 amino acid fragment), and we hypothesize that such fragments, that we have identified in blood and tissues, can trigger immune reactions, which might be the start of more specific reactions, like the ones that eventually eradicate the pancreatic islets and cause type 1 diabetes. Other crop components could also be responsible, as most diets, when referred to as “gluten-free” are in fact “wheat-free”.
We hypothesize that such low-grade inflammation could be reflected in the intra-uterine environment and affect the development of the foetal islets (containing the insulin-producing beta cells),
BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3547 (Published 19 September 2018)Cite this as: BMJ 2018;362:k3547
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