Diabetes Mellitus: More than a Complication of Celiac Disease

Celiac.com 01/07/2023 - First reported in 1925, the coexistence of diabetes mellitus and celiac disease is not a new phenomenon. However, as late as 1984, the connection was viewed with skepticism. Prior to the use of intestinal biopsies, some researchers reported an increase of diabetes mellitus among family members of celiac patients, while others reported contradictory findings.

After development of techniques for taking jejunal biopsies, modestly increased rates of diabetes were reported. These numbers were usually close to 1% of the celiac patients who were reported as having both diseases. When faced with these increased numbers of diabetes mellitus among celiac families and celiac patients, many asserted that certain genetically determined features of the immune system (HLA) were common among people with either condition. Such genetic factors, they argued, might predispose to autoimmune diseases in general, and would therefore be likely to increase the frequency of both conditions within the same families, and sometimes, within the same individual. The issue was further confounded by the overlap between classical symptoms of celiac disease and diabetes mellitus. Thus, a second diagnosis was often overlooked because all symptoms were considered to result from the first condition diagnosed. The reported rates of coexistence thus underrepresented the true overlap.

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It was only through systematic research among large numbers of diabetic patients who were biopsied, along with the development and use of serological testing for celiac disease, that the increased coexistence of these diseases gained recognition during the mid to late 1980s. Still, the dominant view ascribed a common origin for both autoimmune conditions. Thus, when other autoimmune diseases were recognized as overly common among celiac patients, little thought was given to the notion that gluten might trigger more than celiac disease.

Several startling research findings threatened this perspective and offered a new window through which to view celiac disease and autoimmunity in general. Although this work was initially paid little attention, each of several distinct areas of research were building toward a critical mass.

Exploration of intestinal permeability, and its relationship to celiac disease, was investigated throughout the 1990s. This work not only provided convincing evidence for the use of sugar absorption tests to screen for celiac disease in developing nations, it also established that intestinal leakage of food proteins is a consistent feature of active celiac disease.

One spin-off result of this work was to increase the credibility of molecular mimicry as a dynamic that followed the leakage of food proteins into the bloodstream. These foreign proteins were shown to cause immune system reactions that damaged both the foreign proteins and self tissues with similar protein structures.

Meanwhile, another area of research was increasing the use of serum antibody testing, called celiac panels, which soon revealed that celiac disease was dramatically more common than previously believed. These tests also established that the coexistence of celiac disease and diabetes mellitus was also common. When diabetic patients were tested, about 5% were shown to have celiac disease. When celiac patients were tested, about 10% were found to have diabetes mellitus.

Developments in similar serum antibody testing, related other autoimmune diseases, also revealed that compliance with a gluten-free diet, following diagnosis of celiac disease, actually resulted in reductions of these other antibodies. These studies suggested that gluten might actually play a causal role, not only in diabetes, but in a wide range of autoimmune diseases that were previously considered to be coincidentally associated with celiac disease. Hope dawned for many who suffered from a wide range of autoimmune diseases . Simple dietary changes might aid new treatments and bring relief to these many sufferers of autoimmunity. Even in cases where gluten is not the underlying cause, we are gaining understanding of the dynamics by which autoimmunity develops.

The crowning moment, with respect to diabetes, came in January of this year when A.J. MacFarlane, et al. published their findings in the Journal of Biological Chemistry. Their work demonstrated that wheat proteins might be a major causal factor in at least some cases of diabetes mellitus. Rooted in prior animal research that was largely spearheaded by Fraser Scott, this most recent research identified immune reactions, in diabetic humans, against wheat proteins which were also closely linked with the attack on the islet cells of the pancreas. This is an exciting moment for those with type 1 diabetes. Many of them may be aided in the maintenance of islet cell transplants (another new development) through following a gluten-free diet.

This work also provides a potential turning point for everyone who suffers from autoimmunity. Thanks to the recent establishment of celiac disease as very common in North America, we now know that about 1 in 133 Americans have celiac disease. We also know that this common condition is triggered by gluten. This family of grain proteins also appears to cause some, perhaps many, cases of diabetes mellitus.

The evidence against gluten is also growing in the investigation of other autoimmune conditions. It appears that celiac disease will soon be the window through which we will gain a better understanding of autoimmunity, and the gluten-free diet may be the cornerstone of the treatment of many cases of autoimmune diseases.