Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A deceased 59-year-old woman with insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis was autopsied. She had had diabetes mellitus since she was 30 years old, and insulin therapy was started at 34 years. Laboratory findings were as follows: s-GOT 85, s-GPT 31, gamma-globulin 2.45 g/dl. Immunological tests were positive for anti-smooth muscle antibody and anti-ENA antibody with high titers of antithyroglobulin and anti-microsome antibodies. HLA analysis revealed the presence of DR-4. The thyroid biopsy specimen showed microscopic features characteristic of chronic thyroiditis at 52 years of age. She had been repeatedly admitted for the control of diabetes mellitus. She was admitted for the 9th time in June, 1987 following complaints of abdominal pain. After admission, her general condition became gradually worse, and she died of peritonitis in September, 1987. Pathological examination of the liver revealed an expansion of fibrous tissue on Glisson's capsule accompanied by lymphocytic infiltration and was diagnosed to be chronic inactive hepatitis. As for the thyroid gland, fibrous tissue replaced an extensive area of the thyroid gland, and normal thyroid tissue was not observed. Lymphocytic infiltration was less in comparison with that in the previous biopsy. As for the pancreas, atrophy of exocrine pancreatic tissue and fibrous change in interstitial tissue was observed. Lymphocytic infiltration was also seen in the interstitial exocrine tissue but not in the islet. Immunohistochemical examination of the islets using anti-insulin, glucagon and somatostatin antibodies by ABC peroxidase method showed the selective disappearance of B cells in the islets. The pathological changes in the thyroid gland, liver and pancreas suggest that autoimmune mechanism may be involved in the pathogenesis of chronic thyroiditis, chronic hepatitis and IDDM with exocrine pancreatic impairment in this case.
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PMID:[An autopsied case of insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis]. 259 7

Thirty-four members of a single family were studied and 9 of them were found to be suffering from hyperthyroidism associated with diffuse goitre. Exophthalmos was absent and transmission seemed to be independent of HLA type. Four of the 9 were studied prior to treatment but in all cases serum immunoglobulin levels were normal, antithyroglobulin and antimicrosomal antibodies absent, thyroid stimulating antibodies negative and the lymphocyte transformation responses to mitogens not different from those of controls. The results of testing the euthyroid family members were similarly negative, except in the case of a woman with type I diabetes mellitus who showed a low titre of antimicrosomal antibody. Seven of the patients underwent subtotal thyroidectomy. Lymphocytic infiltration of the excised portion was rarely present. Four of the glands were subjected to immunofluorescent and electron microscopy but neither immunosecreting cells nor immune complex deposits were found. These results point to the existence of a non-autoimmune form of goitrous hyperthyroidism, different from Graves' disease.
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PMID:Familial hyperthyroidism without evidence of autoimmunity. 712 78

The NOD/Lt mouse, a widely used model of human autoimmune IDDM, was used to establish the mode of beta-cell death responsible for the development of IDDM. Apoptotic cells were present within the islets of Langerhans in hematoxylin and eosin-stained sections of pancreases harvested from 3- to 18-week-old female NOD/Lt mice (a range of 11-50 apoptotic cells per 100 islets). Immunohistochemical localization of insulin to the dying cells confirmed the beta-cell origin of the apoptosis. Although some islets from age-matched control female NOD/scid mice contained apoptotic cells, virtually all of these cells were insulin negative as determined by immunohistochemistry. The small number of apoptotic insulin-positive cells identified in islets from NOD/scid mice (a range of 0-1 apoptotic cells per 100 islets) was not statistically significant, compared with the numbers recorded in NOD/Lt mice. All dying cells showed the morphological changes characteristic of cell death by apoptosis and stained positively with the TUNEL method for end-labeling DNA strand breaks. The maximum mean amount of beta-cell apoptosis occurring in NOD/Lt mice was at week 15 (50 apoptotic cells per 100 islets), which coincided with the earliest onset of diabetes as determined by blood glucose, urine glucose, and pancreatic immunoreactive insulin measurements. While there was no peak incidence of beta-cell apoptosis throughout the time period studied (weeks 3-18), the incidence of apoptosis decreased at week 18, by which time 50% of the animals had overt diabetes. The low levels of beta-cell apoptosis observed is indicative of a gradual deletion of the beta-cell population throughout the extensive preclinical period seen in this model and would be sufficient to account for the beta-cell loss resulting in IDDM. Apoptosis of beta-cells preceded the appearance of T-cells (CD3-positive by immunohistochemistry) in islets. Lymphocytic infiltration of islets (insulitis) was not detected until week 6. The results show that beta-cell apoptosis is responsible for the development of IDDM in the NOD/Lt mouse and that its onset precedes lymphocytic infiltration of the islets.
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PMID:Apoptosis is the mode of beta-cell death responsible for the development of IDDM in the nonobese diabetic (NOD) mouse. 913 40

Pancreatic tissues were analyzed immunohistologically in patients with autoimmune and fulminant type 1 diabetes (T1D) and control subjects. Both beta and alpha cells were decreased in fulminant T1D, but only beta cells were significantly decreased in autoimmune T1D. Insulitis was seen in both subtypes of T1D, but it remained longer in autoimmune than in fulminant T1D. Lymphocytic infiltration to the exocrine pancreatic tissue was observed only in fulminant T1D, whereas immunologically abnormal findings, such as increased expression of MHC class I molecule and Fas antigen in islet cells and Fas-ligand expression in infiltrating lymphocytes, were detected only in autoimmune T1D. From these findings, together with clinical features, it could be concluded that in autoimmune T1D, beta cells are assumed to be destroyed through a long-standing autoimmune process, whereas in fulminant T1D, beta cells seem to be destroyed very rapidly, probably by a destructive process triggered by viral infection.
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PMID:Insulitis in human type 1 diabetes. 1912 Mar 16