Celiac disease in patients with type-1 diabetes mellitus screened by tissue transglutaminase antibodies in southern Kerala, India
A Jacob, S Kumar
celiac disease, tissue transglutaminase antibodies, type 1 diabetes
A Jacob, S Kumar. Celiac disease in patients with type-1 diabetes mellitus screened by tissue transglutaminase antibodies in southern Kerala, India. The Internet Journal of Nutrition and Wellness. 2008 Volume 8 Number 2.
Type-1 diabetes mellitus (T1DM) is a chronic autoimmune disorder with varying degrees of insulin deficiency resulting from an immune-mediated destruction of pancreatic β-cells, usually presenting in young individuals.T1DM can be associated with other clinical, sub clinical, or potential organ-specific autoimmune diseases. Celiac disease (CD) is an autoimmune enteropathy induced by gluten proteins present in wheat, barley, rye; and characterized by small intestinal lesions of variable severity. In its classic form, CD appears with symptoms and signs of intestinal malabsorption. However, the disease may occur in a silent or latent form. Co-existence of T1DM and CD was first suspected in 1954. The same ‘susceptibility genotypes’ are involved in the etiopathogenesis of diabetes mellitus and CD. In both diseases, genetic susceptibility is associated with the HLA-DQ α1*0501, β1*0201 heterodimer, which preferentially presents gluten-derived gliadin peptides on its antigen-presenting groove to stimulate intestinal mucosal T cells. With the existing identical gene location in both diseases, it seems that CD is more frequent in patients with T1DM than in general population. Using different screening procedures for autoantibodies, the reported prevalence of CD in patients with T1DM ranged from 0.6-16.4%. Among different types of serological tests for screening CD, such as anti-gliadin antibodies (AGAs) and antiendomysial IgA antibody (EMA), tissue transglutaminase antibodies (tTGA) has proved to be a very specific indicator to identify subjects with latent CD. It is well known that clinical CD represents only the tip of the iceberg. The sub clinical disease is not infrequent in the general population and serological tests such as tTGA can be used as markers for the identification of these asymptomatic individuals. In several studies, the sensitivity and specificity of this test compared with biopsy-proven disease were 94% AND 98%, respectively. This is important because the treatment of asymptomatic patients with T1DM having a gluten- free diet seems to have a positive effect on glycemic control and on the growth. Furthermore, it can prevent osteoporosis and the development of autoimmune diseases. The aim of our study was to determine the prevalence of CD in patients with T1DM using tTGA as a screening test.
For the current study, 100 patients with T1DM (58 women and 42 men) from diabetes clinic of Maithri multi specialty hospital, Kerala, as study population and 150 non diabetic healthy people (82 women and 68 men) without having autoimmune and other CD- related diseases as control population were recruited. All patients were interviewed by the doctor about any history of diseases and symptoms compatible with CD and a questionnaire was filled out. After formal consenting, 7ml of blood was collected from each subject. Samples were centrifuged and the serum was separated, divided into two aliquots and immediately stored at -200C .Anti-tissue transglutaminase IgA antibodies were determined by enzyme-linked immunosorbent assay (ELISA) with human recombinant tTGA as antigen, using a commercial kit (Eu-tTG IgA, Eurospital ,Trieste,Italy). Results were considered positive when the tTGA levels were higher than 7 AU/mL. The tTGA serological test is not appropriate for patients with IgA deficiency and due to the prevalence of 2-3% IgA deficiency in general population, the serum IgA levels should be determined before any serological tests such as tTGA. This helps in eliminating false-negative results. The total serum IgA levels was determined by turbidimetry and 1gA deficiency was considered positive when the IgA levels were <70 ng/dl. The tTGA positive and, IgA deficient subjects were clinically evaluated and submitted to upper gastrointestinal endoscopy. Crypt hyperplasia and villous atrophy (VA) were classified as either partial (PVA) or total (TVA), according to Marsh.
The Statistical Package for Social Science (SPSS), version 11.5, was used for the statistical analysis. Simple statistics such as frequency, mean and standard deviation were used. In addition, chi-square, t-test and Mann-whitney U test were used for comparison. The results were considered to have a statistical significance when
Serological screening for CD based on tTGA was performed in 100 patients with T1DM (58 women and 42 men) aged 21.8
The results for patients with T1DM and controls are shown in Figure 1 Statistically significant positivity of tTGA was observed in the T1DM patients when compared to the controls (
Table 1 shows demographic and clinical characteristics of subjects with DM compared with healthy controls. There was no difference based on gender between cases and controls. However, the mean age of controls was significantly higher than the patients with T1DM (
Table 2 represents characteristics of tTGA positives compared with tTGA negatives in patients with T1DM.The mean age of tTGA positive cases was significantly lower than tTGA negative ones (mean difference 7.17;95%CI:0.82-13.52years).Furthermore, the mean age of diabetes diagnosis was lower in tTGA positive than tTGA negative subjects, but was not statistically significant (
The prevalence of CD in patients with T1DM who underwent tTGA testing was 8%. There was a significant difference in frequency of the tTGA positivity between cases and controls. Results of studies in Western, African and Middle- East countries showed high variation of CD prevalence in patients. In European and American countries, the prevalence ranged from 1-8% by serology. A recent study conducted in UK, of total 113 children and adolescents with T1DM, 6.2% were tested antibody positive. In addition, 12.3% of Danish children with T1DM were positive for CD. These values were remarkably higher among Africans. The prevalence of CD in Libya and Algeria was 21.3% and 16.3% respectively. In the Middle-East countries, positive serology tests for CD were detected in 20.9% of Saudi children with T1DM. Apparently, the prevalence of the disease in the present study (8%) is similar to those reported in European countries using serological tests. However, this prevalence is relatively higher than those previously reported in India among patients with T1DM. In a study by Gupta G
Since the control group was representative of general population, where CD may develop at any age, both during childhood or adolescence and is relatively common in the adult and elderly patients, the significant higher mean age of controls than cases does not alter the significant difference of CD prevalence between them.
In the present study, the age of diabetes mellitus diagnosis was lower in tTGA positive subjects compared to tTGA negative ones in patients with T1DM, but the difference was not statiscally significant. However, the tTGA positive cases had a significant lower age than tTGA negative cases. These observations are in agreement with some studies, which revealed that the risk of CD and T1DM is higher in younger age groups than in older ones.
Dermatitis is reported to occur in CD patients especially between 15 and 40 years. In our research, one out of eight (12.5%) tTGA positive patients with T1DM had a positive history of dermatitis (
Diarrhea is another common symptom among CD patients, but none of tTGA positive patients in our study reported chronic diarrhea. As mentioned before, tTGA screens patients with latent CD, in whom there is absence of diarrhea. Furthermore, Indian diet contains wheat as a major component; therefore, exposure to a high level of wheat proteins induces some degree of immune tolerance, leading to milder symptoms. This observation supports recommendation of CD screening in patients with T1DM. It should be noted that the significant difference of chronic diarrhea history between the patients with T1DM and the controls was not the result of age difference between the two groups because there was no association between age and reporting history of chronic diarrhea in our research. Probably this finding is due to higher prevalence of chronic diarrhea in patients with T1DM. In a study performed by Lysy
Longitudinal prospective studies compared with cross-sectional ones can better show the true prevalence of CD in patients with T1DM. Moreover, the benefits of a gluten-free diet (GFD) in these patients are not well established in Iran. Therefore, it is necessary to conduct short-term and long-term clinical randomized control trials to investigate the effect of GFD. Obviously, since most of the patients with CD are asymptomatic, many studies recommend serologic testing for diagnosis of T1D and every two years after that. Thus, the younger individuals with T1DM could benefit from GFD to improve their quality of life.
This study showed the higher prevalence of CD in patients with T1DM than the general population in southern Kerala and the data lend support to recommend regular screening for CD in all patients with T1DM.