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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increasing bulk of evidence suggests that type 1 (insulin-dependent) diabetes mellitus is an autoimmune disease with a strong immunogenetic background. 1st-degree relatives of type 1 diabetic patients, especially HLA-identical individuals, bear an increased risk to develop the disease. The autoimmune reactions are pronounced at the onset of disease where an infiltration of islets with T and B lymphocytes, plasma cells and macrophages can be observed. Autoreactive T lymphocytes play a crucial role among effector mechanisms which finally lead to a selective destruction of pancreatic beta cells. Disease-specific autoantibodies (Ab) include cytoplasmic islet cell Ab (ICA), islet cell surface Ab (ICSA), Ab to the 64KD islet cell protein and Ab to insulin (IAA). As ICA can be detected months or years before the onset of clinical disease, testing of individuals at risk or population screening programs can help to recognize subclinical insulitis. High titers of ICA and high levels of IAA, as measured by radioimmunoassay, indicate a high risk for progression to type 1 diabetes. A blunted first phase insulin response in the i.v. glucose tolerance test is the most sensitive sign of an irreversible metabolic deterioration. It is likely that immunotherapy at a prediabetic state will be more efficacious than its initiation after the clinical manifestation of diabetes. However, the appropriate immunotherapeutical strategies are yet to be worked out.
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PMID:Etiology and pathogenesis of type 1 diabetes. 149 Jun 74

Insulin-dependent diabetes mellitus is the late consequence of a chronic autoimmune disease directed to the B islet cell, that begins long before the hyperglycemic state. Experimental evidence suggests a central pathogenic role for autoreactive T lymphocytes. Immunointervention studies, particularly those using cyclosporin, have shown that it is possible to stop B cell destruction, even at the late stage of overt diabetes. New therapeutic approaches will be focused on the use of specific agents such as monoclonal antibodies and immunotoxins, and on earlier interventions allowed by the detection of genetic and immunological markers of prediabetes.
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PMID:[Immunotherapy of type 1 diabetes]. 149 32

Insulin-dependent diabetes mellitus is preceded by a prodromal phase during which insulin-secreting cells are progressively destroyed by immunological factors. Among genetically predisposed and high risk subjects, this phase of prediabetes can be identified by detection of immunological and metabolic markers. For these prediabetic subjects, specific immunomodulators, without adverse effect, will be available.
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PMID:[Screening and prevention of type 1 diabetes]. 149 33

Type 1, insulin-dependent diabetes mellitus is an autoimmune disease with destruction of beta-cells in islets of Langerhans by activated (antigen-positive) infiltrating mononuclear cells accompanied by serological immune phenomena. The pathological mechanism has not yet been clarified in detail, and some inversion in the proportion of epidermal antigen expression has recently been described in spontaneous diabetes. The BB rat is one of the animal models most closely resembling human type 1 diabetes of autoimmune origin. We compared the class I and class II antigen expression in the islets of Langerhans and in the skin of spontaneously diabetic (BBD) and normoglycaemic (BBND) BB rats in the prediabetic, diabetic and non-diabetic states. Class I and class II antigen expression increased significantly in the islets of BBD rats from prediabetes to diabetes and compared with non-diabetic controls. In the same period, the dermal antigen expression (class I and class II) did not decrease and was not lower in BBD than in BBND animals. These results do not support a loss of activated (antigen-positive) dermal cells at the onset of diabetes in the BB rat and do not show a clear correlation with the antigen expression in infiltrated islets of Langerhans.
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PMID:A comparative study of antigen expression by skin and pancreas in the prediabetic and diabetic state of the BB rat. 157 58

The past decade has seen great advances in our understanding of the pathogenesis of IDDM. This knowledge has led to investigate use of a battery of immunologic, genetic, and metabolic tests for identifying people with prediabetes. Therapies designed to arrest autoimmunity have been associated with incomplete responses and the complications of immunosuppression. Ultimately, we hope that IDDM can be eradicated by inducing tolerance to the diabetogenic autoantigen(s).
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PMID:The pathogenesis, prediction, and prevention of insulin-dependent diabetes mellitus. 161 64

Insulin dependent diabetes (IDDM) has an autoimmune pathogenesis. Included is the presence of antibodies to pancreatic islet cells. The first identified were islet cell antibodies (ICA), detected by indirect immunofluorescence, and which react with all cells within islets. Importantly, the autoantibodies are found several years prior to disease and although a pathogenic role for the autoantibodies is unclear, they have become useful markers of prediabetes. A number of studies of twins discordant for IDDM and of first degree relatives of IDDM patients have established that there is an increased risk for disease in individuals who have ICA, especially when ICA levels are high. This high predictive value of ICA decreases in the general population where the incidence of IDDM is lower than in first degree relatives, and both ICA and the disease risk associated with ICA, appear to be influenced by a genetic susceptibility. This has been sustained in a study of patients with endocrine autoimmunity and ICA (Polyendocrine Study) where the predictive value of very high levels of ICA is less than 50% in patients without a first degree relative with IDDM. Hence, there remain a substantial number of patients with ICA who do not develop disease. From these patients, it was demonstrated that ICA include at least two distinct specificities, one of which is beta cell specific and is not associated with a high risk for IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel considerations on the antibody/autoantigen system in type I (insulin-dependent) diabetes mellitus. 193 Sep 42

Type I (insulin-dependent) diabetes mellitus is a slow autoimmune disease associated with the selective destruction of beta-cells in the islets of Langerhans. Recent studies in humans indicate that autoantibodies to insulin and islets of Langerhans appear years before overt diabetes and identify a normoglycemic prediabetic state. To determine whether type I diabetes mellitus represents a generalized immunologic disorder, we studied the phenotypic characteristics of peripheral blood lymphocytes from all stages, i.e., prediabetic, new-onset diabetic, and long-term diabetic patients, with the anti-2H4 monoclonal antibody CD45R, which defines a human suppressor-inducer subset, and the anti-4B4 monoclonal antibody CDw29, which defines a human helper-inducer subset of peripheral blood lymphocytes. All 22 prediabetic patients had elevated T4+2H4+ (suppressor-inducer) cells and reciprocal depressed T4+4B4+ (helper-inducer) cells compared with healthy age-matched control subjects. In addition, the T4/T8 ratio in prediabetic patients was decreased compared with the age-matched control subjects. The abnormal T4+2H4+ and T4+4B4+ subsets were resolved in 20 new-onset and 15 long-term diabetic patients. Family studies showed that the changes in the 2H4 and 4B4 antigens were not part of an inherited polymorphic determinant, because these markers were normal in unaffected siblings and parents. Ten prediabetic patients were restudied greater than 1 yr after the original analysis and showed the persistence of the observed changes. This abnormal increase in suppressor-inducer cells and decrease in helper-inducer cells among islet and insulin antibody-positive prediabetic patients may be of help in understanding diabetes pathogenesis and may also be an early noninvasive screening tool for the detection of the prediabetic state.
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PMID:Abnormal T-lymphocyte subsets in type I diabetes. 253 73

The presence of cytoplasmatic islet cell antibodies (ICA) and IgG insulin autoantibodies (IgG-IAA) has been observed in the prediabetic state of type 1 (insulin-dependent) diabetes (IDDM). We therefore analyzed the prevalence of these markers in sera from 1117 healthy HLA-typed first-degree relatives (1 degree Rel) of IDDM patients. ICA was determined by indirect immunofluorescence on cryostat sections of human pancreas. For IgG-IAA measurement a competitive solid-phase ELISA was used. ICA were present in 3.5% of 1 degree Rel vs 0.4% of controls (P less than 0.025). The highest frequencies of ICA were found in individuals of IDDM multiplex families (7.7%) and HLA-DR1,3 (5.4%), -DR1,4 (5.8%), and -DR3,4 (6.7%) positive subjects. We therefore conclude that the prevalence of ICA is increased in 1 degree Rel with high genetic risk for diabetes. IgG-IAA occurred in 9.9% of 1 degree Rel vs 1.4% of controls (P less than 0.01). Like ICA, IgG-IAA were significantly increased in a group of subjects being positive for either HLA-DR1,3 -DR1,4, or -DR3,4 (16.5%, P less than 0.01). In multiplex families, however, prevalence of IgG-IAA was not increased. In contrast to ICA there was an additional influence of age and sex: IgG-IAA were found more often in siblings (mean age, 16.6 years; prevalence, 15.0%) than in parents (mean age, 44.1 years; prevalence, 8.3%) of IDDM patients (P less than 0.01). In brothers the prevalence of IgG-IAA is higher than in other 1 degree Rel. Only a weak association between ICA and IgG-IAA was observed in subjects (n = 810) tested for both antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus. 264 70

Since sufficiently long time the average life expectancy in IDDM did not change. Only new data concerning the causes and pathogenesis of the disease may improve such set-back. The most promising field of creating the better insight into etiology of IDDM are molecular pathological studies. This review attempts to summarize the state of art in this area choosing the problems of clinical relevance. Many of them are controversial, disturbing the immunogenetic hypothesis of IDDM etiology, majority positively support this idea. 6 topics are critically discussed in respective sub-chapters: 1) genetic control of autoimmunization processes as pertinent to beta cells; 2) genesis, actions and clinical significance of various types of autoantibodies against autoantigens; 3) character of beta cell antigens; 4) suggested mechanism of beta cell destruction; 5) new idea of prediabetic state and 6) lessons from immunosuppressive therapeutical trials. Author brings the story of etiological mechanisms of IDDM up to date pointing that more direct and specific information is needed to be applicable in practice.
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PMID:[Molecular pathology of insulin-dependent diabetes mellitus (type I)]. 270 36

The author describes his findings pertaining to spontaneous diabetes mellitus in BB rats and the method and results in juvenile alloxan diabetes in neonatal and adolescent Wistar rats of his own inbreeding F8-10. The author presents also the results of attempts to treat juvenile alloxan diabetes in rats by intrafamilial renal-subscapular allotransplants of 2-5 neonatal collagenase nondigested pancreases. Six of eleven BB females developed latent or manifest insulin dependent diabetes mellitus during the third to fourth month of life. An intraperitoneal injection of alloxan to 2-5-day-old rats causes, after two months of prediabetes, latent or manifest disease, in particular in males. In one-two-month adolescent fasting F6--10 inbred rats (Wistar strain) intravenous injection of 50 mg/kg alloxan causes diabetes mellitus with hyperglycaemia (20-60 mmol/l), glycosuria, polyuria, arrested growth, development of cataract and early death due to pulmonary or intestinal infection. The author tries to prevent these sequelae and complications by insulin therapy or intrafamilial allotransplantations of 2-5 neonatal, collagenase nondigested pancreases beneath the renal capsule, using two-three--week immunosuppression with Cyclosporin A combined with Azathioprine. The author proves permanent cure, histologically and functionally, by repeated allotransplantation which, however, due to the intense thymolymphatic immunological barrier in adolescent rats is less frequent than cure repeatedly achieved by the author in adult diabetic rats.
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PMID:[Spontaneous and experimental models of human juvenile diabetes mellitus]. 275 53


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