Norman Swan: One chronic disease that many people wish was preventable is type 1 diabetes, which usually comes on in childhood. It's an autoimmune disease where the child's immune system destroys the cells in the pancreas which produce insulin. It's possible to identify children at risk of type 1 diabetes. They have a parent or sibling with the condition and a tissue-type which makes them susceptible. There is some evidence that the proteins in cow's milk may increase the risk as well, which is why a research group in Helsinki has carried out a trial of what's called hydrolysed formula which breaks down the complex proteins into simpler ones. On the line from Finland is Mikael Knip who is Professor of Paediatrics at the University of Helsinki. Welcome to the Health Report.

Mikael Knip: Thank you.

Norman Swan: How strong was the evidence that cow's milk is a risk factor before you did this study?

Mikael Knip: So there were studies in animal models, autoimmune diabetes, suggesting that the use of a hydrolysed formula decreased the incidence of diabetes, and in addition there were epidemiological data from huge studies indicating that an early exposure to conventional formulas, which all are based on cow's milk, increased the risk of type 1 diabetes.

Norman Swan: And this, as I suggested in the lead, is a suggestion that you get some sort of activation of the immune system from these proteins, that was the theory?

Mikael Knip: Yes, that was the idea.

Norman Swan: So tell us about this study.

Mikael Knip: So, as you mentioned, the participants were newborn infants with at least one family member affected by type 1 diabetes, and in addition carrying a genotype predisposing to type 1 diabetes. This is an international study. We recruited participants in 15 countries, including Australia, and altogether we had 2,159 participants when we started.

Norman Swan: So it's a big definitive study, and you followed them up for 11.5 years?

Mikael Knip: That is correct, yes.

Norman Swan: And they were breastfed as well, so the women…the mothers were encouraged to breastfeed. This is really talking about what you weaned the baby onto after you stopped breastfeeding.

Mikael Knip: Yes, so actually the duration of breastfeeding was in the study longer than in the background population.

Norman Swan: So they did more than they would otherwise have done.

Mikael Knip: Right.

Norman Swan: And so they were randomised onto hydrolysed formula, and a fairly standard hydrolysed formula that you can buy over-the-counter in your supermarket or chemist?

Mikael Knip: Yes, it is a formula that has been used for a long time in the treatment of babies with cow's milk allergy.

Norman Swan: And there is some question about whether it's beneficial there, but we are not dealing with that today. What did you find?

Mikael Knip: So first we looked at the appearance of diabetes associated autoantibodies by the age of seven years. We had a pilot study in Finland indicating that the intervention will decrease the appearance of autoantibodies, but in the larger TRIGR study we couldn't see that, we couldn't find any difference.

Norman Swan: And just to explain here, the autoantibodies are the first sign that you are really heading towards type 1 diabetes in the next year or two.

Mikael Knip: That is correct, and if it is positive for two of such autoantibodies you are at a very high risk of progressing to clinical disease.

Norman Swan: So it didn't affect those. Did it affect the incidence of type 1 diabetes?

Mikael Knip: No, we continued the follow-up, and we couldn't see any difference in the appearance or progression to type 1 diabetes by the age of 11.5 years.

Norman Swan: So the theory is dead really. I mean, nobody is ever going to do a bigger study than this for 11.5 years, you've proved it, that unfortunately the hydrolysed formula doesn't work.

Mikael Knip: Yes, of course that is…and after that we were looking for…and on the other hand I think that we did get a definite answer to our research question, and there will be no other intervention trial of this type.

Norman Swan: So are there are other ways of preventing type 1 diabetes? People talk about nasal insulin, introducing insulin early to these children. What can parents look for for prevention now?

Mikael Knip: So currently there is no known effective way to prevent type 1 diabetes in risk individuals. There are some other options that will be tested. I can tell you that there are indications that coxsackie B viruses may trigger the disease process, and anti-diabetogenic coxsackie-virus vaccine is under development but it will take several years before that can be tested in a large-scale study. Another option that is discussed is to start an intervention with the early introduction of a probiotic into the diet of the infant.

Norman Swan: With the hope of manipulating the immune system through the gut.

Mikael Knip: Right, yes, that's the idea there.

Norman Swan: So there's some hope there, the virus that might trigger the diabetes, or changing the immune system in the early years that hopefully might sort that out. Well, some hope there. And is there any indication at all, very briefly, for hydrolysed formula? I think from the Australian researchers here they suggest that it doesn't really prevent allergy, does it?

Mikael Knip: So I think that there is no reason to use hydrolysed formula if you have a risk baby, that is the conclusion that we can make out of the TRIGR study.

Norman Swan: So the manufacturers might have to look for another market. Mikael Knip, thank you very much for joining us.

Mikael Knip: Thank you.

Norman Swan: Mikael Knip is Professor of Paediatrics at the University of Helsinki in Finland.