Alimentary tract and
pancreas
Alimentarni trakt
i pankreas
ARCH
GASTROENTEROHEPATOL 2002; 21 ( No 3 – 4 )
Letter to Editor
Coeliac disease and
diabetes mellitus type 1: Connection between the two autoimmune disease or
concidence?
Celijačna bolest i dijabates tip 1: Udruženost dve autoimune bolesti ili koincidencija?
( accepted October 10th, 2002 )
Gradimir Golubović, Ratko Tomašević
Department of Gastroenterology, Clinical Hospital Center Zemun-Belgrade.
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Sir, many autoimmune diseases are associated with coeliac disease: diabetes mellitus type 1, dermatitis herpetiformis, autoimmune hepatitis, thyroiditis and rheumatoid arthritis (1). According to Candell et al. patients with diabetes mellitus type 1 demonstrate a significant propensity to coeliac disease which is approaching 10% in the adults (2). Immune phenomena are considered responsible for both diseases, although their genetic connection cannot be excluded with certainty (3). We report a patiente with diabetes mellitus type 1 and associated coeliac disease in which gluten-free diet led to the improvement of glycaemic profile and lessen the insulin requirements.
CASE REPORT Forty years old man with 10 years history of poorly controlled diabetes mellitus type 1 presented with history of abdominal pain, recurrent diarrhoea and weight loss. He experienced digestive problems for about several months. At admssion he was pale and emaciated (weight 52kg, height 186cm) with meteorismus. Laboratory analyses demonstrated hypochromic anemia with hemoglobin level of 86g/l, low serum iron ( 3.1 mcg/l), hypokalemia ( 3.1mmol/l), and hypoalbuminemia (29.5g/l). C-peptide was 0.12 IU. Proximal gastrointestinal endoscopy combined with multiple duodenal mucosal biopsies demonstrated total villous atrophy, crypt hypertrophy, heavy infiltration of lamina propria with CD4 lymphocytes and macrophages. Serum anti-transglutaminase IgA antibody concentration was very increased ( 100 IU/l; normal <5). HLA haplotype was HLA DQ2.
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Diabetes mellitus type 1 and coeliac disease Gastroenterološka sekcija SLD-
01739, 2002.
Instituted gluten-free diet led to gradual but definite amelioration of abdominal pain, normalisation of stool frequency and consistency, improvements of glycaemic profile with singificant reduction of insulin doses, and normalisation of laboratory indices.
COMMENT The association of coeliac disease and diabetes mellitus is well recognised Their association is liaised to their genetic loci which are closely related (4). Both belong to the group of autoimmune diseases. In coeliac disease the initiator and perpetuator of autoimmune process are wheat proteins, gliadins. They belong to the family of glutamine and proline rich proteins which are excellent donors of glutamine to tissue transglutaminase ( tTG). This enzyme catalyses cross-linking reaction between substrate proteins giving the rise of gliadin to gliadin complexes. In the absence of adequate receptors, tTG is built in these gliadin to gliadin aggregates thus becomming the main autoantigen in coeliac disease (5). Anti-tTG antibodes are the most significant serologic indicator of coeliac disease with sensitivity and specificy exceeding 95% (6).
An increase of inducable tTG activity may cause posttranslocational modification of various tissue proteins in different organs: heart, thyroid, sking thus causing the formation of antigenic neo-epitopi, de novo antigenic targets. This posibly lead to variety of autoimmune reactions in HLA DQ2 and DQ8 positive individuals. Early diagnosis of coeliac disease and instituted gluten-free diet may thus reduce the risk of at least one autoimmune disease, diabetes mellitus type 1 (8). On the contrary, patients with various autoimmune diseases are under the risk to suffer of coeliac disease as well (9). In diabetes mellitus type 1, the third class of antibodies is related to the enzyme glutamic acid decarboxilase (anti-GAD antibodies) whereas the target autoantigen in coeliac disease is tTG what links both target enzymes via glutamins, their main substrate (10).
In conclusion, all adult and paediatric cases of diabetes mellitus type 1 has to be sceened for anti-tTG antibodies. This may help in diagnosing either latent or silent coeliac disease what in turn may help in better diabetic control.
REFEREENCES:
1.Collin P, Kaukinen K, Valimaki M, Salmi J. Endocrinological disorders and coeliac disease. Endocr Rev 2002; 23:464-83.
2.Candell Y, Rigante D, Marietti G et al. Diagnosis of coeliac disease in type 1 diabetes mellitus. Gut 2002; 51 (Suppl 3):A98.
3.Scuppan D, Ciccocioppo R. Coeliac disease and secondary autoimmunity. Dig Liv Dis 2002; 32:13-5.
4.Di Sabatino A, Bertrandi E, Casadei M et al. Phenotyping of peripherial blood lympnocytes in adult coeliac disease. Ummunology 1998; 95:572-6.
5.Schupan D. Current concepts of coeliac disease pathogenesis. Gastroenterology 2000; 119:234-42.
6.Piacentini M, Colizzi V. Tissue transglutaminase: apoptosis vs autoimmunity Immunol Today 1999; 20:130-4.
7.Doyle HA, Mamula MJ. Post-translocational protein modification in antigen recognition and autoimmunity. Trends Immunol 2001; 22:442-9.
8.Ventura A, Maggazu G, Greco L.ion of exposure of gluten and risk for autoimmune disorders in patients with coeliac disease. Gastroenterology 1999; 117:297-303.
9.Schupan D, Hahn EG. Coeliac disease and its link to type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2001; 14:597-605.
10.Hummel M, Bonifato E, Stern M et al. Development of coeliac disease associated antibodies in offspiring of patients with type 1 diabetes. Diabetologia 2002; 43:1005-11.