Coeliac disease and type 1 diabetes mellitus: epidemiology, clinical implications and effects of gluten-free diet

Abstract

Coeliac disease (CD) is a gluten sensitive chronic enteropathy that affects between 1:100 and 1:300 individuals in the general population of the western world [1]. It is characterised by an increased mortality [2]. Autoimmune disorders such as autoimmune thyroiditis, type 1 diabetes (T1DM), Addison’s disease, autoimmune liver disease, and Sjogren’s syndrome occur much more frequently in patients with CD than in the general population. The clinical relevance of autoimmunity in coeliac disease is threefold: first, it further deteriorates the clinical course of coeliac disease; second, patients might present only with symptoms of secondary autoimmunity and this could favour the diagnosis of minor coeliac disease; and third, gluten withdrawal could improve the control of some associated autoimmune disorders [3]. The associations between CD and T1DM was recognized over 30 years ago, particularly by paediatricians. The prevalence of CD among adults and children with T1DM varies in different geographical populations and is observed to range between 1 and 11 % [4–7]. This close association has been ascribed to the same HLA pattern, namely HLA-DQ2 and/or DQ8, which predisposes individuals to both disorders. Recently, Greco et al. performed a study in the western part of Sicily where they saw that the prevalence of CD among patients with T1DM is 4.5 %. They studied 492 subjects (children and adult patients) with T1DM who had been followed-up regularly at their diabetes unit over a fiveyear period. They found CD in 22 patients [8]. In addition, in accordance with previous studies, they confirmed that CD is more prevalent in female subjects with T1DM than in males [5] and that the age of onset of T1DM is younger in patients with double the disease than in those with diabetes only [6]. None of Greco’s patients presented gastrointestinal symptoms, only two patients presented extraintestinal symptoms (short stature, anaemia and hyposideraemia) and one female patient developed concurrent herpetiformis dermatitis. In fact, one quarter of CD patients with T1DM are totally asymptomatic but the remainder show gastrointestinal symptoms (such as diarrhoea, anorexia, constipation, vomiting, abdominal distension, pain and malnutrition) or extraintestinal symptoms. The most frequent clues in extraintestinal signs are short stature and iron-deficiency anaemia which are present in approximately 50 % of cases; however, fatigue, pubertal delay and vitamin deficiencies are also common, especially in children. Other systemic signs suggesting CD in T1DM patients are a reduced BMI, diminished mass bone, bleeding due to vitamin K deficiency and raised levels of transaminases [9]. CD symptoms (both gastrointestinal and extraintestinal) seem to be much more frequent in children than in adolescents and adults [10]. In the majority of cases (more than 90 %), the diagnosis of T1DM precedes that of CD and Greco et al. confirmed this finding. However, some studies reported that T1DM onset can frequently occur in patients already diagnosed with CD [5]. These data suggest the importance of screening for CD for patients with T1DM at the time of diabetes diagnosis and then annually for several years after diagnosis. In particular, antibody positivity for CD may appear within 6 years from the initial diagnosis of T1DM [4]. Serologial screening for CD consists of endomysial antibodies, antibodies against tissue transglutaminase and deamidated gliadin peptide antibodies. When these antibodies are positive, small intestinal biopsy is mandatory. CD histology is characterized by different degrees of villous A. Marchese E. Lovati F. Biagi (&) G. R. Corazza First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Piazzale Golgi, 19, 27010 Pavia, PV, Italy e-mail: f.biagi@smatteo.pv.it