The Link Between Type 1 Diabetes and Celiac Disease

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A number of studies in recent years have noted that type 1 diabetes and celiac disease seem to colocalize within families and individuals, but the reason why is not entirely clear.

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Enter this study, appearing in the journal Pediatrics, which has begun to clarify these muddy waters.

First, what we already know. We know that kids with Type 1 diabetes are more likely than other kids to develop celiac disease. We also know that both type 1 diabetes and celiac disease have a strong genetic component. For example, there is 75% concordance of celiac disease in identical twins compared to 10% in fraternal twins.

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The genetic underpinnings of both diseases are strongly linked to human leukocyte antigen (HLA) haplotype – with certain variations of HLA-DR3 and HLA-DR4 being principally responsible. So – is it fair to say that the reason we see type 1 diabetes and celiac disease running together is that they are both driven by the same genetic risks?

To answer this question, researchers undertook an ambitious project. At 6 US and European centers, 424,788 newborns underwent genetic screening for these high-risk HLAs. Two percent, 8,676 kids, were found who had high-risk genetics. These kids were then followed prospectively for about 5 years to see who would develop the relevant disease-associated antibodies over time.

The big question was whether the kids who developed both sets of antibodies would be the key to understanding the common underpinnings of the two diseases.

But we need to understand something about those kids first.  Take a look at this graphic.

Each dot represents one child with EITHER anti-islet cell antibodies, anti-tissue-transglutaminase antibodies or both.

Each dot represents one child with EITHER anti-islet cell antibodies, anti-tissue-transglutaminase antibodies or both.

Each black dot here, represents a kid with at least one of the relevant antibodies.

Now, I’ll color the kids with type 1 diabetes antibodies in red.

Kids with islet autoantibodies colored red.

Kids with islet autoantibodies colored red.

Now let’s layer in the kids with celiac disease antibodies in blue. 

Kids with islet autoantibodies colored red, tissue-transglutaminase antibodies colored blue, and both colored green.  In the green box: the "extra" kids with both sets of antibodies, beyond the expected chance co-occurrence.,

Kids with islet autoantibodies colored red, tissue-transglutaminase antibodies colored blue, and both colored green.  In the green box: the "extra" kids with both sets of antibodies, beyond the expected chance co-occurrence.,

Why are some dots green? Because by chance alone, some kids are going to be unlucky twice – there is bound to be some overlap. But what the authors observed was more “green” kids than would be expected.  See those extra green dots in the box?  That's the observed data, as compared to the expected data. About 20 extra kids with both sets of antibodies.

Those extra kids confirm that there is some common factor tying type 1 diabetes and celiac disease together.

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But extensive genetic tests did NOT find the culprit. That means there is probably an environmental factor that is predisposing to both of these diseases.

What that factor is… is unclear. But it probably isn't gluten ingestion.  The study showed that while type 1 diabetes predisposed kids to celiac disease, the reverse was not true. Kids with celiac disease were no more likely to subsequently develop type 1 diabetes.

So while we don't know the exact cause yet, the implication is that with further research, we may kill off two diseases for the price of one.