Letters to the Editor

ANTIGLIADIN ANTIBODIES AT ONSET OF DIABETES IN CHILDREN

The rise in new cases of type 1 diabetes (T1D) in genetically susceptible individuals over the past half century has been attributed to numerous environmental “triggers” or promoters such as enteroviruses, diet, and most recently, gut bacteria. No single cause has been identified in humans, likely because there are several pathways by which one can develop T1D. There is renewed attention to the role of the gut and its immune system in T1D pathogenesis based largely on recent animal studies demonstrating that altering the gut microbiota affects diabetes incidence. Although T1D patients display dysbiosis in the gut microbiome, it is unclear whether this is cause or effect. The heart of this question involves several moving parts including numerous risk genes, diet, viruses, gut microbiota, timing, and loss of immune tolerance to β-cells. Most clinical trials have addressed only one aspect of this puzzle using some form of immune suppression, without much success. The key location where our genes meet and deal with the environment is the gastrointestinal tract. The influence of all of its major contents, including microbes, diet, and immune system, must be understood as part of the integrative biology of T1D before we can develop durable means of preventing, treating, or curing this disease. In the present review, we expand our previous gut-centric model based on recent developments in the field.

Coeliac disease is the life-long intolerance to dietary gluten, usually characterized by severe damage to the small-intestinal mucosa. The widespread use of sensitive diagnostic tools, such as the serum anti-gliadin and the anti-endomysial antibodies, has shown not only that coeliac disease is one of the commonest disorders in Western countries but also that this condition is characterized by a higher degree of clinical variability than previously thought (typical, atypical and silent forms). The existence of a latent-potential coeliac disease and even a gluten-sensitive disease with immunological activation of an otherwise normal small-intestinal mucosa has recently been postulated. An increased prevalence of coeliac disease in a number of other disorders has also been reported in both children and adults. The reasons for such a wide clinical heterogeneity are still poorly understood but are likely to depend on both genetic and environmental factors. Further investigations are required to evaluate the impact of undiagnosed, clinically milder forms of coeliac disease on the well-being of the population.