Insulin-dependent diabetes mellitus and coeliac disease

Cronin, Cornelius C.; Shanahan, Fergus

doi:10.1016/s0140-6736(96)09153-2

Cited by 202 publications

(149 citation statements)

References 23 publications

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“…Among these, T1D is set apart because the prevalence of CD among T1D patients has been reported to be about 10 times higher compared to that in the general population. 44 Therefore, it is plausible to hypothesize that this frequent association is due to common determinants that operate in both diseases. Indeed, there are at least seven common genetic loci determining the susceptibility of both diseases.…”

Section: Discussionmentioning

confidence: 99%

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

et al. 2011

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Two common chronic childhood diseases-celiac disease (CD) and type 1 diabetes (T1D)-result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions. INTRODUCTIONWith an approximate prevalence of 1.0% in Western countries, celiac disease (CD) is one of the most common lifelong chronic disorders. 1 CD and type 1 diabetes (T1D) form a significant sector of childhood diseases with high rate of co-occurrence. 2 Both diseases are autoimmune in origin and develop as a result of complex pathological mechanisms, involving several common genetic, environmental and immunological factors. Among these, the common susceptibility loci of HLA and other immune system-related genes, 3 permeability changes in the small-bowel mucosa, 4 and association with wheat consumption 4,5 are prominent. Both diseases are increasing in most regions of the world, 6,7 as are several other autoimmune diseases, but the actual cause of the disease remains unknown. However, several recent studies have highlighted the role of environmental and social changes that have taken place over the last several decades. 8,9 The central event in the pathogenesis of CD is damage to the small intestinal mucosa that occurs after ingestion of gluten or related prolamins in genetically susceptible individuals. During this process, several morphological and immunological alterations have been demonstrated in the small-bowel mucos...

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Section: Discussionmentioning

confidence: 99%

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

et al. 2011

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“…HLA DQA1*0501 and DQB1*02 alleles encoding for a distinctive HLA-DQ2 heterodimer molecule is found in at least 90 % of the patients, compared to 20±30 % of the control subjects [10]. Because this HLA-DQ2 molecule is also overrepresented in Type I diabetes, the frequent occurrence of coeliac disease in subjects with diabetes is believed to be connected with genetic predisposition [1]. In the Childhood Diabetes in Finland study, 43 % of children with diabetes and 24 % of population-based control subjects had the HLA-DQB1*02 allele [5].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1 * 02 allele

et al. 2001

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Increased prevalence of coeliac disease in patients with Type I diabetes has been widely reported in Caucasian populations, with figures for prevalence varying from 1.0 to 7.8 % [1]. Certain HLA genotypes (especially, those positive for DR3-DQ2 haplotype) are more frequent in both of these diseases. First-degree relatives of patients with Type I diabetes have an increased risk for developing diabetes, a risk that is proportional to the degree of shared HLA risk alleles. It

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“…The withdrawal of gluten reverses not only the intestinal, but also the skin lesions in most dermatitis herpetiformis patients. Many other pathological conditions, such as autoimmune disorders (insulin-dependent diabetes mellitus type 1, thyroid disorders, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, alopecia, vitiligo, Addison's disease, Sjögren's syndrome, IgA nephropathy and IgA deficiency), [55][56][57][58][59][60][61][62][63][64][65] idiopathic disorders (primitive dilated cardiomyopathy, atopy and inflammatory bowel disease) [66][67][68] and chromosome disorders (Down, Turner and Williams syndromes), [69][70][71] display a strong association with CD. The importance of diagnosing the subclinical form of CD associated with these disorders is twofold because a gluten-free diet not only prevents the clinical manifestations and complications of CD but also sometimes improves clinical symptoms of the associated disorders (Table 3).…”

Section: Introductionmentioning

confidence: 99%

Celiac disease: diagnostic criteria in progress

2011

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Until a few years ago, celiac disease (CD) was thought to be a rare food intolerance that was confined to childhood and characterized by severe malabsorption and flat intestinal mucosa. Currently, CD is regarded as an autoimmune disorder that is common in the general population (affecting 1 in 100 individuals), with possible onset at any age and with many possible presentations. The identification of CD is challenging because it can begin not only with diarrhea and weight loss but also with atypical gastrointestinal (constipation and recurrent abdominal pain) and extra-intestinal symptoms (anemia, raised transaminases, osteoporosis, recurrent miscarriages, aphthous stomatitis and associated autoimmune disorders), or it could be completely symptomless. Over the last 20 years, the diagnostic accuracy of serology for CD has progressively increased with the development of highly reliable tests, such as the detection of IgA tissue transglutaminase and antiendomysial and IgG antideamidated gliadin peptide antibodies. The routine use of antibody markers has allowed researchers to discover a very high number of 'borderline' cases, characterized by positive serology and mild intestinal lesions or normal small intestine architecture, which can be classified as potential CD. Therefore, it is evident that the 'old celiac disease' with flat mucosa is only a part of the spectrum of CD. It is possible that serology could identify CD in its early stages, before the appearance of severe intestinal damage. In cases with a positive serology but with mild or absent intestinal lesions, the detection of HLA-DQ2 and HLA-DQ8 can help reinforce or exclude the diagnosis of gluten sensitivity.

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Insulin-dependent diabetes mellitus and coeliac disease

Cited by 202 publications

References 23 publications

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1 * 02 allele

Celiac disease: diagnostic criteria in progress

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