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DDW research highlights celiac disease symptom disconnect

May 22, 2019

Studies also show evidence of how frequently patients are exposed to gluten, especially on the weekends

By Amy Ratner, Medical and Science News Analyst

Research presented at Digestive Disease Week in San Diego this week painted a complicated picture of celiac disease, including evidence that patients are frequently exposed to gluten, especially on the weekends, many have symptoms every day and symptoms are not a good indicator of whether someone has ongoing intestinal damage.

Meanwhile, research led by Marie Robert, MD, Beyond Celiac chief scientific officer and professor of pathology and medicine at Yale University School of Medicine, found that neither results of blood work measuring celiac disease antibodies, symptoms, nor how well a patient was keeping to the gluten-free diet predicted whether follow-up biopsy results would show intestinal damage.

Additionally, one study presented raised the possibility of a non-invasive test for celiac disease based on chemically defined gluten peptides in the circulatory system and ultimately measured in urine. Researchers had set out to determine whether analysis of chemical peptides in urine could distinguish people with celiac disease from people without the condition.

Another study that stepped away from the research laboratory and into the kitchen showed that cooking classes helped adults with celiac disease stick to their gluten-free diet and consequently improve their quality of life.

These were among topics covered in lectures in the first session devoted to celiac disease at DDW. Details of studies presented in a session the second day, posters featuring investigations at various stages and more will be covered in additional research news posts. DDW is an annual conference for physicians, researchers and academics in the fields of gastroenterology, hepatology, eendoscopy and gastrointestinal surgery.

Symptom disconnect

Researchers from the Mayo Clinic compared the frequency and severity of patients’ symptoms to the results of their celiac disease blood tests and intestinal biopsies. More than a third of 1,276 patients had  gastrointestinal symptoms every day. When tiredness was included in the measure of frequency of symptoms, more than half reported having a symptom every day.

When the relationship between positive blood tests and symptoms was reviewed, those with positive tests had slightly more overall symptoms and slightly more tiredness. Positive blood tests were not associated with the frequency or severity of any other symptoms.

Diarrhea was the only symptom the predicted intestinal damage found when a biopsy was done.  

The study found symptoms of celiac disease are inconsistent in predicting the results of a blood tests and biopsies. This inconsistency led researchers to conclude symptoms should not be the only thing used to evaluate a patient’s response to a gluten-free diet. However, frequent and severe diarrhea should prompt a reevaluation of the condition of the intestine, they noted.

Similarly, in Robert’s multinational study reviewing biopsies of patients done intially and at follow up, persistent symptoms were found on the second biopsy in 78 percent of patients with damaged villi and 66 percent of patients who had normal biopsy.

More than half of 184 patients in the study who had a second biopsy had persistent damage. In addition to the findings related to symptoms and damage, the study was designed to show physicians how to  correctly take samples when a patient needs a second biopsy so changes are not missed.

The gluten-free diet in real life

Although celiac disease experts know that gluten regularly gets into the gluten-free diet, how often this happens in real life is not well understood. To get a better real world picture, researchers from universities in Canada and Argentina used urine and stool tests to measure gluten immunogenic proteins (GIP) from 23 celiac disease patients following their normal diet for four weeks. The availability of these tests enables researchers to quickly and accurately measure how much gluten has been consumed. Study participants had been following a gluten-free diet for at least two years. 

They found that 96 percent excreted gluten in urine or stool at least once in four weeks. Forty five percent of all 92 urine samples collected and 26 percent of all 92 stool samples were positive for GIP.

Researchers took samples in a way that allowed them to determine when gluten was consumed on weekdays versus weekends and found that 91 percent of study participants had gluten exposure on the weekend, possibly because they ate away from home more often.

Patients with symptoms and without had a similar number of positive gluten tests, 3 times over the course of the study versus 2.5 times. The study concluded high frequency of consuming gluten was not influenced by whether patients had symptoms or not.

The longer the study went on, the more evidence that study participants were eating gluten was found. Researchers attributed this to patients becoming more relaxed about their gluten-free diets. This kind of change in behavior as a direct result of being in a clinical trial is called the Hawthorne effect. In other clinical trials in which gluten exposure was monitored, the opposite has occurred with patients becoming stricter about what they ate because their diets are being observed.

When patients learned that evidence showed gluten was getting into their diets, they often responded that they were following a strict gluten-free diet. “’ I am doing my best,’’ Juan Stefanalo, the author who presented the study, quoted them as saying. One person in the study who consumed gluten only once was perplexed by how it could have happened, until she recalled the she had gone to Mass in a different church from the one where she normally got a gluten-free communion host. She realized the communion wine she did drink was cross-contaminated, Stefanalo said.

Peter Green, MD, director of the Celiac Disease Center at Columbia University,  asked if the study evaluated whether the gluten transgressions being detected with the urine and stool tests had caused the study participants any real harm. “We are concerned we are driving these people crazy,” he said in a question and answer period following the lecture.  Green noted that researchers are increasingly looking at the effect anxiety about the gluten-free diet has on patients.

Chemistry and celiac disease monitoring

Stanford University scientists have discovered chemically-defined gluten peptides that might lead to a new way of monitoring celiac disease. The study they presented marks the first time a chemically defined gluten peptide from the circulatory system was identified in a living organism.

About 40 percent of people in the general population have the genes for celiac disease, leading to the question of why only 1 percent develop celiac disease. Some other factor clearly contributes to the onset, said study author and presenter Nielson Weng. Many chemical transformations are part of disease development, he noted. When wheat is eaten it goes through mechanical and chemical digestions leaving partially digested peptides, some of which are seen as toxic by the immune system of those who have celiac disease.

In the small study based on 16 samples, researchers found that urinary gluten peptides in those with celiac disease had different biological and chemical properties compared to those who don’t have the condition. Now they are evaluating the potential use of the peptides as a non-invasive biomarker of celiac disease status.

Urine samples were collected from patients who wanted to know if they had celiac disease. The patients fasted overnight, then urine samples were collected. Next, study participants were challenged by eating a gluten-containing bagel after which another urine sample was collected. Patients also had biopsies of the small intestine done to determine if they had celiac disease. Scientists were able to differentiate urine from patients with celiac disease from urine from those without celiac disease based on the chemical structures of the peptides.

Cooking up a better way to follow the gf diet

Adults who took cooking classes that emphasized healthy, naturally gluten-free grains subsequently did a better job following the gluten-free diet and had an improved quality of life, according to a pilot study by Columbia University researchers. Twelve men and women with celiac disease who were beginner to intermediate cooks took two cooking classes conducted by a chef and dietitian. The classes focused on providing motivation for cooking, then giving the study participants the tools to follow through on that motivation.

The classes detailed the risks of a gluten-free diet that lacked healthy gluten-free whole grains and included too many processed gluten-free products. Cooking at home was presented as a way to achieve a healthy diet, rich in gluten-free whole grains and variety.

Participants in the study provided their medical history, information on their quality of life, symptoms, anxiety and depression and how well they followed the gluten-free diet.

After the classes, participants reported significantly improved overall celiac disease quality of life, fewer social limitations and concerns about their future health. They also had better diet adherence and less depression, but anxiety increased, something the study noted needs to be further explored.

They also had more positive expectations of the benefits of home cooking, more confidence in their ability to cook for themselves and others and increased ability to identify whole grain and gluten-free foods.

The study could serve as a model for cooking classes in other places, perhaps beginning at other celiac disease centers, said Randi Wolf, PhD, Columbia Teachers College, the study author who presented at DDW.

“We should also look at the effects of cooking-based education interventions on long-term diet adherence and quality of life, as well as long-term measures of mucosal healing and the development of other autoimmune diseases,” Wolf said.


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