Can Wheat Cause Type 1 Diabetes?

You might think so after reading this headline:

Type 1 diabetes linked to immune response to wheat

Press release headlines are designed to elicit a response, a desire to read the actual article. But most people never get passed the press release because the actual science is boring or difficult to understand in the manner it is published.

Here is the press release as published:
Scientists at the Ottawa Hospital Research Institute and the University of Ottawa have discovered what may be an important clue to the cause of type 1 diabetes. Dr. Fraser Scott and his team tested 42 people with type 1 diabetes and found that nearly half had an abnormal immune response to wheat proteins. The study is published in the August 2009 issue of the journal Diabetes.

Early in life, the immune system is supposed to learn to attack foreign invaders such as viruses and bacteria, while leaving the body's own tissues and harmless molecules in the environment alone (including food in the gut). When this process goes awry, autoimmune diseases and allergies can develop. Type 1 diabetes is an autoimmune disease that occurs when the immune system mistakenly attacks the pancreas, the organ that regulates blood sugar. Dr. Scott's research is the first to clearly show that immune cells called T cells from people with type 1 diabetes are also more likely to over-react to wheat. His research also shows that the over-reaction is linked to genes associated with type 1 diabetes.

"The immune system has to find the perfect balance to defend the body against foreign invaders without hurting itself or over-reacting to the environment and this can be particularly challenging in the gut, where there is an abundance of food and bacteria," said Dr. Scott, a Senior Scientist at the Ottawa Hospital Research Institute and Professor of Medicine at the University of Ottawa. "Our research suggests that people with certain genes may be more likely to develop an over-reaction to wheat and possibly other foods in the gut and this may tip the balance with the immune system and make the body more likely to develop other immune problems, such as type 1 diabetes."

In a commentary accompanying the paper, diabetes expert Dr. Mikael Knip of Finland said "These observations add to the accumulating concept that the gut is an active player in the diabetes disease process."

Dr. Scott's previous research has shown that a wheat-free diet can reduce the risk of developing diabetes in animal models, but he notes that more research will be required to confirm the link and determine possible effects of diet changes in humans. Research is also needed to investigate links with celiac disease, another autoimmune disease that has been linked to wheat.
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This research was funded by the Juvenile Diabetes Research Foundation and the Canadian Institutes of Health Research. The authors include Dr. Majid Mojibian, Dr. Habiba Chakir, Dr. David E. Lefebvre, Jennifer A. Crookshank, Brigitte Sonier and Dr. Erin Keely, as well as Dr. Scott. Patients were enrolled at The Ottawa Hospital and the Children's Hospital of Eastern Ontario.

An estimated 246 million people have diabetes worldwide. Type 1 diabetes is the most severe form, representing about 10 per cent of all cases. Insulin injections can help control blood sugar levels in those affected but there is no cure.

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Celiac is another autoimmune disorder. It has long been known if you have 1 autoimmune problem, your risk for another is much higher. In Type 1 diabetics about 5% or more have also been diagnosed with Celiac (I worked with one family who's daughter was diagnosed with BOTH at the same time). This study noted that the genetic subset for Celiac was not present in the tested patients (by the way, a very small number of test subjects) and this immune response was not the same as that for Celiac.

Here is an abstract of the actual article in the Journal of Diabetes (published by the American Diabetes Association). I'm a member of ADA but I was unable to access the full text of the article online.

Diabetes-Specific HLA-DR–Restricted Proinflammatory T-Cell Response to Wheat Polypeptides in Tissue Transglutaminase Antibody–Negative Patients With Type 1 Diabetes
Majid Mojibian, Habiba Chakir, David E. Lefebvre1, Jennifer A. Crookshank, Brigitte Sonier, Erin Keely and Fraser W. Scott

Abstract
OBJECTIVE There is evidence of gut barrier and immune system dysfunction in some patients with type 1 diabetes, possibly linked with exposure to dietary wheat polypeptides (WP). However, questions arise regarding the frequency of abnormal immune responses to wheat and their nature, and it remains unclear whether such responses are diabetes specific.

RESEARCH DESIGN AND METHODS In type 1 diabetic patients and healthy control subjects, the immune response of peripheral CD3+ T-cells to WPs, ovalbumin, gliadin, α-gliadin 33-mer peptide, tetanus toxoid, and phytohemagglutinin was measured using a carboxyfluorescein diacetate succinimidyl ester (CFSE) proliferation assay. T–helper cell type 1 (Th1), Th2, and Th17 cytokines were analyzed in WP-stimulated peripheral blood mononuclear cell (PBMNC) supernatants, and HLA was analyzed by PCR.

RESULTS Of 42 patients, 20 displayed increased CD3+ T-cell proliferation to WPs and were classified as responders; proliferative responses to other dietary antigens were less pronounced. WP-stimulated PBMNCs from patients showed a mixed proinflammatory cytokine response with large amounts of IFN-γ, IL-17A, and increased TNF. HLA-DQ2, the major celiac disease risk gene, was not significantly different. Nearly all responders carried the diabetes risk gene HLA-DR4. Anti-DR antibodies blocked the WP response and inhibited secretion of Th1 and Th17 cytokines. High amounts of WP-stimulated IL-6 were not blocked.

CONCLUSIONS T-cell reactivity to WPs was frequently present in type 1 diabetic patients and associated with HLA-DR4 but not HLA-DQ2. The presence of an HLA-DR–restricted Th1 and Th17 response to WPs in a subset of patients indicates a diabetes-related inflammatory state in the gut immune tissues associated with defective oral tolerance and possibly gut barrier dysfunction.

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What does that mean for regular people? There is a possibility that people with Type 1 diabetes show a autoimmune response to wheat that is NOT Celiac. But this is a correlation result, NOT cause & effect. The headlines could easily be misconstrued to suggest eating wheat causes Type 1 diabetes. Nothing could be further from the truth. While this might be one potential trigger in someone who is genetically susceptable, there are many folks with genetic potential who eat wheat and never develop Type 1 diabetes. I'd like to see what happens if they open up this screening to a larger number of people with Type 1 diabetes and include first degree relatives who do NOT have Type 1 diabetes.