KEYSTONE, COLO. — All patients with new-onset type 1 diabetes should be screened for serologic evidence of celiac disease in the form of IgA tissue transglutaminase autoantibodies and, if seronegative and asymptomatic, screened again at least biannually until age 10 years, according to Dr. Marian Rewers.
Rescreening every other year is warranted because a sizeable minority of affected patients does not manifest celiac autoimmunity for several years or more after diabetes onset, Dr. Rewers asserted at a conference on the management of diabetes in youth.
Small bowel biopsy is appropriate in transglutaminase autoantibody-positive patients with symptoms attributable to celiac disease, said Dr. Rewers, professor of pediatrics and preventive medicine at the University of Colorado, Denver, and clinical director of the Barbara Davis Center for Childhood Diabetes. These include diarrhea, weight loss, abdominal pain, malnutrition, growth failure, pubertal delay, chronic fatigue, erratic blood glucose levels, and osteopenia. A finding of villous atrophy on intestinal biopsy is the definitive diagnostic test for celiac disease.
A lifelong gluten-free diet is strongly recommended in biopsy-positive individuals. It results in mucosal healing and complete clinical resolution in most patients. But if initiation of the diet is delayed in symptomatic patients, they may never catch up developmentally in terms of growth and bone density.
In contrast, intestinal biopsy shouldn't be recommended in asymptomatic screen-positive diabetes patients unless their tissue transglutaminase autoantibody level is high enough to confer a greater than 90% probability of a positive biopsy. The higher threshold for biopsy in asymptomatic patients is warranted because a negative biopsy in the setting of a low to intermediate autoantibody level gives a false sense of security that there is no future risk of overt celiac disease, according to Dr. Rewers.
He and his coinvestigators have analyzed a handful of the most widely utilized serologic transglutaminase tests and, for each test, quantified the autoantibody levels necessary to attain a greater-than-90% positive predictive value regarding biopsy results (J. Pediatr. 2005;146:494-9).
The celiac disease-screening recommendations he presented are the ones utilized at the Barbara Davis Center. They are more aggressive than those of the American Diabetes Association, which currently recommends serologic screening only for type 1 diabetes patients who are symptomatic for celiac disease (Diabetes Care 2008;31:12-54).
Dr. Rewers and his Denver colleagues argue for universal screening in children with type 1 diabetes based on the high prevalence and potentially serious implications of celiac disease in this population. In the general population, 1 in 100 children has IgA transglutaminase autoantibodies, but that figure climbs to 1 in 10 among those with type 1 diabetes. Most of these affected diabetic children are asymptomatic and thus are identifiable only through screening. And there is concern about the still-unclear long-term consequences of untreated subclinical celiac disease, he said at the conference, which was sponsored by the Barbara Davis Center, the University of Colorado, and the Children's Diabetes Foundation at Denver.
He and his coinvestigators have demonstrated in a study of 134 children with an average 4-year history of type 1 diabetes that the 71 who had screening-detected asymptomatic celiac autoimmunity also had a significantly lower body weight and body mass index and increased markers of bone turnover, compared with the antibody-negative group. Yet bone mineral density scores in the two groups were similar.
In all, 25 seropositive patients claimed to go on a gluten-free diet. At the 1-year follow-up, they had significantly lower glycosylated hemoglobin levels and higher BMIs than did those on a regular diet. Their autoantibody levels decreased but in most cases did not normalize, which suggested problems in compliance with the demanding diet. Bone turnover markers didn't change on a gluten-free diet over this relatively short time span (J. Pediatr. 2007;150:461-6).
“So the jury is still out on whether all patients with celiac autoimmunity need to be on a gluten-free diet and how stringent the diet should be,” Dr. Rewers concluded.
Rescreening is needed as some patients don't manifest celiac autoimmunity for several years after diabetes onset. DR. REWERS