Patients who are diagnosed with "potential" celiac disease appear metabolically similar to those who actually have the disease, researchers say.

Among 29 "potential" patients, 24 were classified as having the disease on metabonomic analysis, Ivano Bertini, MD, of the University of Florence in Italy, and colleagues reported in the Journal of Proteome Research.

"Our results demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of a gluten-free diet," they wrote.

In genetically susceptible patients, celiac disease is triggered by ingestion of gluten, a protein found in wheat, barley, and rye. It has been shown to have a well-defined metabonomic signature, the researchers said.

Often, its clinical symptoms will disappear with a gluten-free diet.

Yet the condition remains underdiagnosed, experts say, partially because some patients who have immunological abnormalities don't show clear celiac disease on jejunal biopsy.

So to determine the metabolic profile of these potential patients, the researchers used magnetic resonance metabolic profiling to analyze the biochemical markers in the blood and urine of 61 patients with celiac disease, 29 with potential disease, and 51 healthy controls.

They found that those with potential disease largely shared the same profile as those with the confirmed disease, and that the biochemical markers in both groups differed significantly from those of the healthy individuals.

For instance, of the 29 potential celiac patients, 24 were classified as having the disease while five were classified as controls.

The researchers saw hardly any differences in serum metabolites between overt and potential disease. They said it appears that in untreated patients, glycolysis is somehow impaired, which explains both a lowering of lactate levels and an increase in glucose levels.

On the other hand, there were more metabolites in urine that differentiated between overt and potential disease, the key areas being those originating from gut microflora. The researchers said it has been reported that particular bacterial strains may work in conjunction with gluten to cause an increased immune response that is responsible for the development of celiac.

The researchers noted that the similarity in serum and dissimilarity in urine markers "allow us to hypothesize that while the alterations in the urine profile may follow intestinal damage, gluten intolerance exists as such before an evident intestinal damage occurs."

Finally, the researchers performed a citrulline assay, which revealed significantly lower levels in potential patients than in controls. Yet interestingly, endoscopy didn't show any sign of villous atrophy, they said (P<0.001).

The data suggest that "potential celiac disease subjects are, indeed, not potential at all. They ... appear metabolically similar to overt celiac disease ... without any histological evidence of intestinal damage."

If this hypothesis holds, the researchers wrote, "the core result from our investigation would be that metabolomics can detect celiac disease also when its clinical manifestation is not fully evident."

They also emphasized the importance of a gluten-free diet in these potential patients.

Source

Journal of Proteome Research: Bernini P, et al "Are patients with potential celiac disease really potential? The answer of metabonomics" J Proteome Res 2010; DOI: 10.1021/pr100896s.