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)

Effective fuel metabolism is dependent on balances among exogenous and endogenous fuel availability, the glucagon/insulin ratio, and tissue insulin sensitivity. Diabetes mellitus results when imbalances occur. The resultant metabolic derangement is accompanied by abnormalities in carbohydrate, protein, and fat metabolism. The two most common forms of diabetes are insulin dependent (IDDM) and noninsulin dependent (NIDDM). IDDM is an autoimmune disease, characterized by insulinopenia and ketosis. NIDDM is related to impaired insulin secretion, defective tissue sensitivity, and abnormalities in glucose transporter proteins. This article describes normal fuel metabolism and traces the abnormal metabolic processes that lead to both IDDM and NIDDM.
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PMID:Normal fuel metabolism and alterations in diabetes mellitus. 184 Sep 66

It is well established that insulin-dependent diabetes (IDDM) is an autoimmune disease with a strong genetic link to the HLA locus. It is less well understood, however, how the destruction of the insulin-producing beta cells is effected and why neighboring non-beta islet cells are spared. Also incompletely explained are the observations that, unlike other autoimmune diseases such as multiple sclerosis, IDDM does not preferentially affect females, the incidence of the disease is highest among young adults, and there are temporal correlations between the onset of the disease and emotional trauma. We have addressed some of these questions by using transgenic mice that constitutively express the MHC class I antigen Dd in the beta cells of the pancreas. Although both male and female Ins.Dd mice expressed equivalent amounts of the Dd protein only the males developed diabetes. The diabetes in the males could be reversed by castration, and the normoglycemic females became diabetic following either ovariectomy and the implantation of a slow-release pellet containing testosterone or the inclusion of dexamethasone in the drinking water. In contrast, transgenic mice that expressed the herpes simplex virus type 1 glycoprotein D in the pancreatic beta cells were normoglycemic and showed no obvious histopathological consequences. The observation that the beta-cell dysfunction by the increased expression of the MHC class I protein Dd cannot be induced by the herpes viral protein suggests that the cellular damage is related to a specific structure or function of the MHC proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Male-specific beta-cell dysfunction and diabetes resulting from increased expression of a syngeneic MHC class I protein in the pancreata of transgenic mice. 196 48

IgA nephropathy (IgAN) has been associated with HLA-DR4. We have recently described two non-allelic Taq I DQ beta gene-associated fragments sized 2.0 kb (T2) and 6.0 kb (T6), which strongly associate with DR4. T2 represents a polymorphism of the DQ beta gene and has been redesignated DQw8 (10th International HLA Workshop). The origin of the T6 fragment has not been determined, but probably represents a polymorphism of either the DQ beta or DX beta gene. When present together T2 and T6 define a subgroup of DR4 subjects at high risk of developing autoimmune disease. We have, therefore, studied DQ beta gene polymorphisms in IgAN. The DR antigen distribution was similar in IgAN and normal controls. The T2+/T6+ phenotype was present in 49% patients with IgAN compared to 15% of controls [P less than 0.0001, chi 2 = 32.8, Cramer's V = 0.41; relative risk = 5.5 (range, 2.8-11.0)]. Seventy-two percent of DR4+ IgAN patients and 29% of DR4+ controls were T2+/T6+ (P = 0.007, chi 2 = 17.0). These findings confirm the hypothesis that disease susceptibility genes are important in IgAN, and suggest that the putative gene(s) are located within or near to the DQ subregion. Moreover, similar DQ beta gene associations have been found in IDDM and pemphigus vulgaris, pointing to a common immunogenetic mechanism predisposing to several autoimmune diseases.
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PMID:HLA DQ region gene polymorphism associated with primary IgA nephropathy. 196 92

New immunogenetic markers are demonstrated for type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. These markers are detected by restriction fragment length polymorphism (RFLP) analysis of HLA-D region genes and genes for the tumor necrosis factor alpha (TNF alpha). By analysing haplotypes transmitted to diabetic probands in families and comparing them with haplotypes that are only transmitted to healthy siblings it is shown that DQw8-DQB1 gene variation is important for susceptibility on DR4 haplotypes. Analysis of this DQw3 split in patients with Hashimoto's thyroiditis reveals that the other DQB1 gene variation, namely DQw7, displays the strongest association with Hashimoto's thyroiditis. This DQB1 variation has several implications for susceptibility and/or pathogenesis of both autoimmune endocrine diseases. Novel polymorphisms for TNF alpha are detected and it is shown that heterozygosity for TNF polymorphisms is significantly associated with type I diabetes and Graves' disease. Furthermore, DR4 haplotypes transmitted to diabetic probands possess significantly more the 10.5 Kb fragment in contrast to DR4 haplotypes transmitted only to healthy family members. This genetic polymorphism raises functional issues in susceptibility to autoimmune disease and can lead to a new explanation of the enigmatic HLA-association with a variety of diseases.
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PMID:Immunogenetic markers for autoimmune diseases of the endocrine system. 197 65

We studied the association of a T-cell receptor (TcR) beta restriction fragment length polymorphism (RFLP) and a new TcR-alpha RFLP with insulin-dependent (Type I) diabetes mellitus. This study is part of our effort to find new non-HLA disease genes involved in this chronic organ-specific autoimmune disease. Distribution of a 9.2 kb and a 10.0 kb diallelic TcR beta 2 RFLP was not different in diabetics and controls. A new TcR-alpha RFLP, which gave a 2.7 kb Hind III restriction fragment (A2 allele) was found with a frequency of 0.78 in a population of 78 IDDM patients, compared to 0.68 in 68 control subjects (X2 = 3.62, p = 0.057). In 11 multiplex families studied, a high prevalence of the A2 allele was also observed, but cosegregation with the disease was not seen. Our data suggest that a TcR beta 2 RFLP is not associated with the disease, whereas a particular T-cell receptor alpha germline RFLP (A2 allele) is increased in Type I diabetics although formal proof of linkage is lacking. HLA typing reconfirmed that the HLA-DR4 specificity and the DQ allele HLA-DQw8 are primary risk markers in insulin-dependent (Type I) diabetes mellitus.
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PMID:TcR-alpha and TcR-beta dialellic RFLPs in insulin-dependent (type I) Caucasian diabetic patients. 198 28

Alopecia areata universalis developed gradually over nine months in a 25-year-old woman. When her scalp hairs were totally lost and other body hair began to fall out, the symptoms of insulin dependent diabetes mellitus, an organ-specific autoimmune disease, developed rapidly and progressed to diabetic coma. Alopecia did not regress after the metabolic state improved following insulin therapy. Biopsy of the scalp skin revealed significant reduction of the total number of hair bulbs and prominent lymphocyte infiltration into the remaining hair follicles. Insulin dependent diabetes mellitus and alopecia areata universalis are both thought to be related to the autoimmune mechanism and sometimes coexist. However, simultaneous development of these two disorders is extremely rare.
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PMID:Simultaneous development of insulin dependent diabetes mellitus and alopecia areata universalis. 201 15

It has now become clear that certain HLA antigens are associated with disease susceptibility more than any other genetic markers. Insulin-dependent diabetes mellitus (IDDM or type I) is an HLA-associated condition. Moreover, there is evidence to show that IDDM is a genetically programmed autoimmune disease. Studies of the HLA-DR region have shown a strong association with IDDM, with over 90 per cent of IDDM patients possessing DR3 and/or DR4. Although the HLA-DR region is a major component in the inherited disease susceptibility, it is not the only gene region involved. Recent studies demonstrated that HLA-DQ may be more closely linked to the disease locus than HLA-DR. Sequence analysis of the HLA-DQ3 gene products suggest that a single amino acid (aspartic acid) at position 57 is uniquely important for determining susceptibility or resistance to IDDM. Although there is a strong association of certain HLA loci with IDDM, it may not explain nor account for all the genetic susceptibility to the disease. It seems that 60 per cent of the genetic basis of IDDM is related to the HLA gene (chromosome 6) and another 40 per cent is non-HLA-associated (i.e., chromosomes 2, 7, 11, and 14). Even though great progress has been made in the understanding of the genetics of IDDM, the mode of inheritance of the disease remains controversial. The present review discusses various aspects of the autoimmune process believed to be involved in pancreatic beta cell destruction in individuals genetically susceptible to IDDM. The possible modes of inheritance and new data regarding estimated risks of transmitting the disease are presented.
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PMID:Insulin-dependent diabetes mellitus and immunogenetics: maternal and fetal considerations. 205 68

Type 1 (insulin-dependent) diabetes mellitus results from an autoimmune disease which is directed to insulin-secreting islet cells. In man, it is closely associated to definite major histocompatibility complex alleles. The islets are infiltrated by inflammatory cells (insulitis). Anti-islet cell autoantibodies are present in most patients and represent a valuable marker for the autoimmune reaction. The major role of autoreactive T lymphocytes has been demonstrated in animal models of spontaneous insulin-dependent diabetes (the BB rat and the NOD mouse). Such pathophysiological concepts already have clinical applications. The presence of anti-islet cell antibodies identifies patients with type 1 diabetes of slow onset who initially present with non-insulin dependent diabetes. In the same respect it is now feasible to predict the possible occurrence of diabetes in 'at risk' subjects (such as siblings of a diabetic patient) on the basis of HLA typing and the presence of markers of anti-beta cell immunity. Lastly, both in animal models and in human diabetes, it has been demonstrated that immune intervention can alter the course of anti-islet autoimmunity. From these results one may hope in the future to get preventive treatment of type 1 diabetes before the onset of metabolic disturbances.
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PMID:[Type 1 diabetes mellitus, autoimmune disease: physiopathologic aspects and practical applications]. 206 84

Insulin-dependent diabetes mellitus (IDDM) is associated with several DR3- or DR4-containing ancestral haplotypes (AHs). Using pulsed field gel electrophoresis (PFGE), long range maps of 35 haplotypes have been derived and classified. Two diabetogenic DR3-containing AHs (8.1 and 18.2) possess deletions in the central non-HLA region; these have not been found on non-diabetogenic AHs tested to date. In addition, 8.1 and 18.2 also carry other deletions not found on other AHs. Three DR4 containing AH lack a Not I site, which may imply excision of an unidentified gene. These and other data suggest that deletions may be relevant to the pathogenesis of autoimmune disease, possibly through causing quantitative differences in autoimmune responses involved in IDDM. The MHC contains several regions of potential interest in relation to susceptibility to IDDM; these may explain the association with only certain DR3- and DR4-carrying AH and DR3,4 heterozygosity in terms of cis and trans interactions. On the other hand, the class II region may be particularly important in protection.
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PMID:Characterization of MHC ancestral haplotypes associated with insulin-dependent diabetes mellitus: evidence for involvement of non-HLA genes. 209 82

Another autoimmune disease was found to accompany insulin dependent diabetes mellitus (IDDM) in 14% of the young diabetics (n = 14) studied. Thyroid autoimmune disease was the most common of the accompanying autoimmune diseases, and was detected in 11% (n = 15) of the patients. Two thirds of the IDDM patients with autoimmune thyroiditis were hypothyroid, one was hyperthyroid, and 20% lacked detectable thyroid antibodies when thyroid disease was diagnosed. Coeliac disease was found in 2% of the patients, and one had Addison's disease. Autoantibodies were found in one third of the patients. Thyroid microsomal antibodies were detected in 22% of the patients, IgA anti-gliadin in 11%, gastric parietal cell antibodies in 3% and rheumatoid factor in 7%. Autoimmune disease and the relevant autoantibodies coexisted in 11% of the patients. Autoimmune disorders and autoantibodies were not associated to any particular HLA type. The distribution of the HLA-types in the patients was unusual in that the frequency of HLA-DR3 was not increased. The value of autoantibody tests in the diagnosis of functional disorders of the thyroid and of coeliac disease are discussed.
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PMID:Autoantibodies and autoimmune diseases in young diabetics. 213 5


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