Studies of celiac disease and type 1 diabetes expanding understanding of both

April 15, 2020

Celiac disease antibodies, gluten introduction and role of viruses explored

By Amy Ratner, Medical and Science News Analyst

Scientists are following the long term development of celiac disease in multiple studies that look at children at risk for celiac disease.

Researchers from the Colorado Center for Celiac Disease at Children’s Hospital Denver are collaborating with the Barbara Davis Center in work on the Diabetes and Autoimmunity Study of the Young (DAISY), the Environmental Determinants of Diabetes in the Young (TEDDY), and Autoimmunity for Kids (ASK). The studies screen children for celiac disease, type 1 diabetes and other autoimmune conditions.

DAISY

The DAISY study recently marked 20 years of research and Edwin Liu, MD,  director of the Colorado Center for Celiac Disease at Children’s Hospital Colorado and member of the Beyond Celiac Scientific Advisory Council, at the recent Columbia Celiac Disease Symposium, outlined what scientists have learned through a number of studies related to celiac disease.

Liu’s outline, as well as that presented by Daniel Agardh, MD, adjunct professor at the Lund University diabetes and celiac unit and a TEDDY researcher, provide a broad overview of current thinking about celiac autoimmunity and development of celiac disease.

DAISY studies have led to better understanding of the role HLA-DQ2 and DQ8 genes and of the natural history of tTG antibodies. Studies have shown that not all those with the genes or all those who have the anti-tissue transglutaminase (tTG) antibodies related to celiac disease develop the condition.  Antibodies can be transient, fluctuating or persistent, Liu said.

Children participating in DAISY fell into a variety of categories broadly defined as celiac disease autoimmunity including those who had: celiac disease confirmed through biopsy or high antibodies; positive antibodies and negative or equivocal biopsies, called potential celiac disease; fluctuating antibody levels over time; or persistent antibodies but no biopsy and no gluten-free diet.

A 20-year prospective study of 1339 children with genetic risk factors for celiac disease found that although more than 5 percent of children may experience a period of celiac disease autoimmunity, not all children develop celiac disease or require gluten-free diet.

Seroconversion: development of detectable antibodies in the blood, which are then measured to diagnose a disease.

Additionally, the 2017 study showed a rapid rate of seroconversion in those at risk that suggests the majority will develop celiac disease in childhood. The study found a rapid rate of development of celiac disease in the first five years of life, with incidence slowing after the age of 10. By the age of 15, slightly more than 3 percent of Denver children followed for up to 20 years had developed celiac disease, a rate about three times higher than that typically cited for the overall U.S. population.

“Are we in the middle of a celiac disease epidemic?” Liu asked at the Columbia symposium.

TEDDY

TEDDY studies are being done by a consortium of six clinical centers created to develop and to identify environmental causes of type 1 diabetes in genetically susceptible individuals. Children with type 1 diabetes have an increased risk of also developing celiac disease, leading some TEDDY studies to focus on the connection.

The role of genes, diet and infections have all been explored in TEDDY investigations. Agardh said evidence has shown that:

  • The age at which gluten is first introduced is not associated with development of celiac disease, but the amount of gluten a child eats before the age of 5 does play a role, with increased amounts leading to increased risk.

The University of Chicago recommends that at-risk infants should eat less than 5 grams of gluten-containing food on average per day beginning when food is introduced to a baby at 4-to-6 months and continuing until the age of 2. That equals less than an ounce of pasta or one slice of bread. The recommendations are based on evidence that suggests amount of gluten fed to infants at risk for celiac disease may influence whether they actually get the disease.

  • Infections early in life may play a role in the development of celiac disease, especially gastrointestinal infections. Enterovirus infections are associated with increased celiac disease autoimmunity. The interaction between enterovirus and the amount of gluten consumed by children need to be confirmed in larger studies.

Related: Extra half slice of bread a day may increase chance of celiac disease in at-risk children

Looking toward research in the next five years, Agardh said scientists need to study the natural history of tTG to better understand development of antibodies and onset of celiac disease. Additionally, more research is needed to determine whether there is an association between season of birth and celiac disease autoimmunity and celiac disease to identify if there are possible risk modifying factors for babies before they are born or immediately after birth.

Finally, researchers need to look for bacterial and viral associations with celiac disease autoimmunity and celiac disease and the interaction between the amount of gluten consumed and HLA genes.

ASK

The ASK study is a free health screening program open to all Colorado children, from one to 17-years-old, designed to detect celiac disease and type 1 diabetes. In the case of celiac disease, the goal of the research is to help children with undiagnosed celiac disease get the best treatment and monitoring. For type 1 diabetes, it is to identify children likely to get the condition months to years before they get sick.

ASK monitors these children and educated family members about preventing serious complications. Additionally, the study is investigating safe, novel interventions to prevent diabetes.

“Our mission with ASK is to bring awareness to the community of the importance of childhood diabetes and celiac disease—the two most common autoimmune diseases of childhood—and to reduce health risks of delayed diagnosis of these diseases,” the study website explains.

About 50,000 children between the ages of 1 and 17 are expected to be screened over three years. About 900 children with celiac disease are expected to be identified through ASK screening.

The Early Career Investigator grant awarded by Beyond Celiac to Marisa Gallant Stahl, MD, is funding research that follows up on ASK. The study is evaluating the impact of celiac disease on the health and quality of life of children who are identified through a mass screening program. Since these children have no obvious symptoms of celiac disease, they would be unlikely to be diagnosed otherwise.

Related: Investigating screening for celiac disease in children

The study will address the dilemma of weighing the potential health problems related to undiagnosed celiac disease in asymptomatic children with the potential burden of the gluten-free diet, which can be socially limiting and lead to problems with anxiety, depression and a general reduction in quality of life, plus some nutritional concerns.

The study has two aims. One is to determine whether children found through screening will see improvement in height, weight, nutritional measures and symptoms that might not have been associated with celiac disease prior to screening. The second is to determine whether their health-related quality of life is affected. The study will test the hypothesis that improvement will occur in both areas and that screening for and treating of celiac disease in the general pediatric population can reduce morbidity. The U.S. Preventive Services Task Force in 2017 concluded it did not have enough evidence to make a recommendation on general population screening for celiac disease and this study can help provide some of that evidence, according to Stahl.

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