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)

As we have discussed previously (Horn et al. 1988a; Erlich et al. 1989b; Horn et al. 1988b), there are no unique class II sequences associated with IDDM, which suggests that "normal" class II alleles confer susceptibility. Given the estimates of concordance--under 50% of monozygotic twins and approximately 15% (Tattersol, Pyle 1972 and Thomson 1988) for HLA-identical sibs--, it is not surprising that some unaffected individuals contain putative susceptibility alleles. Perhaps some environmental "triggering" agent, such as viral infection (Yoon, this volume), is required for the disease to develop in susceptible individuals. Other non-MHC linked genes which contribute to susceptibility may account for the difference in concordance rates for monozygotic twins and for HLA-identical sibs. In the nonobese diabetic mouse and the BB rat models for IDDM, non-MHC susceptibility loci have been identified and mapped (Hattori et al. 1986; Colle et al. 1981), but in humans the analysis of non-MHC candidate loci (i.e., the T cell receptor) has thus far failed to reveal any other susceptibility loci. In general, the HLA-linked genetic susceptibility to IDDM, as well as to other autoimmune diseases, appears to be associated with specific combinations of class II epitopes (e.g., alleles, haplotypes, or genotypes) rather than with specific individual residues or epitopes. Understanding the role of these predisposing sequences will require structural analysis of the class II molecules as well as in vitro and in vivo functional studies of interactions with putative autoantigens and T cell receptors. In the meantime, DNA typing offers the potential for identifying individuals at high risk for IDDM.
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PMID:HLA class II polymorphism and genetic susceptibility to insulin-dependent diabetes mellitus. 212 92

To examine whether the presence of thyrogastric autoantibodies is associated with an increased susceptibility towards developing type 1 diabetes we have tested for thyroid (microsomal and thyroglobulin) and gastric-parietal cell antibodies in 86 pairs of identical twins, 47 discordant and 39 concordant for type 1 diabetes. Autoantibodies were detected in both twins of a pair in 35 and in neither twin in 45 pairs. In only 6 pairs (3 discordant) was there a discrepancy in the antibody results between co-twins. The frequency of antibodies was similar in twin pairs discordant, (21/44, 48%), and concordant, (14/36, 39%), for diabetes. Thyrogastric antibodies were not more frequent in pairs that were female, diagnosed above the age of 20, or had HLA DR3 as opposed to DR4. We conclude that thyrogastric autoantibodies are common in both type 1 diabetic patients and their non-diabetic identical twins. Their presence appears to be genetically determined but does not increase the susceptibility of developing diabetes. The presence of autoantibodies does not appear to indicate a separate aetiological type of diabetes.
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PMID:Are thyrogastric autoantibodies associated with an increased susceptibility to developing type 1 (insulin-dependent) diabetes? A study in identical twins. 212 77

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

Insulin dependent diabetes mellitus is an autoimmune disease with HLA-related genetic susceptibility. There is a latent phase before overt disease. During this phase islet cell antibodies (ICA) as a marker of humoral autoimmunity are detected and i.v. glucose tolerance test (IVGTT) is decreased. The aim of our work was to correlate IVGTT, HLA typing and ICA testing in all siblings of IDDM patients in order to identify high risk subjects (HRS). IVGTT showed significantly lower insulin levels in siblings vs controls (P less than 0.0001). This phenomenon could be caused by HLA unrelated genetic predisposition to low insulin secretion. Insulin level values of ICA+ siblings were lower than those of ICA- siblings, even if the difference was not significant.
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PMID:[Immunogenetic and functional study of first-degree relatives of patients with type I diabetes mellitus for identifying prediabetic subjects]. 213 76

The increased binding in vitro of CD3 CD4 T-lymphocytes from type 1 (insulin-dependent) diabetic patients to beta-cell membrane antigens compared to lymphocytes from control subjects was previously shown to be a marker of cell-mediated immunity, called diabetic rosettes. In the present study diabetic rosettes were detected in some subjects at risk for type 1 diabetes (first degree relatives of type 1 diabetic patients or nondiabetic subjects with previous transient hyperglycaemia). The mean number of lymphocytes adherent to beta-cells (beta-CL) was significantly higher in subjects at risk for type 1 diabetes than in age- and sex-matched control blood bank donors (P less than 10(-6]. This number of beta-CL was higher in type 1 diabetic patients than in subjects at risk (P less than 10(-6], and one-way analysis of variance by rank (Kruskal-Wallis) revealed that the three populations (controls, diabetics, and risk subjects) were different in terms of beta-CL values (P less than 0.001). The percentage of subjects at risk that had a positive test (arbitrarily defined as a beta-CL value higher than the 95th percentile of 228 controls) was 20%. No difference was observed between the two subgroups of subjects at risk in terms of either mean +/- SEM of beta-CL or percentages of individuals with a positive test. These diabetic rosettes were slightly associated with acute insulin response to iv glucose lower than the 5th percentile of controls (immunoreactive insulin at 1 +/- 3 min, 250 pmol/L; by chi 2, P = 0.04) and with HLA DR 3/4 heterozygosity (by chi 2, P = 0.04). They were not associated with islet cell antibodies (regardless of the threshold for positivity, expressed in Juvenile Diabetes Foundation units), insulin autoantibodies, activated (HLA DR+) T-lymphocytes, or sex. A statistical association was detected between HLA DR 3/4 heterozygosity and a low acute insulin response to iv glucose (by chi 2, P less than 0.003). The preliminary (2-yr) longitudinal follow-up revealed that out of five islet cell antibody-positive subjects who progressed to type 1 diabetes, three displayed beta-CL values higher than the 90th percentile of controls. Diabetic rosettes could, thus, be detected in some individuals at risk for type 1 diabetes as a marker of cell-mediated immunity.
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PMID:Beta-cell cytoadherent lymphocytes in some subjects at risk for type 1 (insulin-dependent) diabetes: progression to diabetes within 2 years. 214 83

The highest risk for the development of type I diabetes resides with first-degree relatives of the diabetic proband, this risk being in the order of 2.9%, 6.6% and 4.9% for parents, siblings and children of the proband, respectively. The major genetic markers associated with the development of insulin-dependent diabetes mellitus (IDDM) is the possession of the HLA alleles DR3/DR4 and more recently the absence of aspartate in the 57th position on the beta-chain of the HLA DQ gene (HLA DQ beta Asp 57 negative). The most important auto-immune marker for predicting preclinical IDDM is the presence of high titres (greater than 40 Juvenile Diabetes Foundation units) of islet cell antibodies (ICA), while the finding of insulin auto-antibodies (IAA) is a good predictive marker in children less than 5 years of age. The presence in a susceptible individual of ICA plus IAA is a better predictor of impending IDDM than the presence of either of these two markers alone. Antibodies which precipitate an islet membrane protein (MW 64K) are highly sensitive and specific markers of preclinical IDDM. The presence of 64K antibodies may well be the most important predictive marker of impending IDDM in the future. The progressive decline of the first phase of insulin secretion in response to an intravenous glucose challenge is associated with the onset of IDDM within 18 months. Of the immunotherapeutic agents at present used in clinically manifest IDDM, azathioprine has been shown to be ineffective in increasing the remission phase, while the value of nicotinamide is controversial.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Can we predict and/or prevent type I diabetes? 221 82

Based on repeated fluoroangiographic examinations in a group of 28 children with type I diabetes mellitus the authors observed progressing diabetic retinal changes. At the end of the three-year observation period they found progress in 32% of the children. They investigated influence of risk factors such as age, duration of the basic disease, its metabolic compensation, sex and HLA typing on the development of diabetic retinopathy.
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PMID:[Risk factors for diabetic retinopathy in children and adolescents with type I diabetes mellitus]. 222 53

In the present paper, an extension of segregation analysis is proposed using information on the joint segregation of two unlinked markers conditional on the disease status in nuclear families, in order to consider two-locus models with one locus linked to the first marker and the other linked to the second marker. We propose tests for examining evidence for the effect of genes located at these two loci and whether this effect is multiplicative or not. This method is then applied to a sample of IDDM families typed for the HLA and Gm markers to test, in addition to a factor of the HLA region, the potential involvement of the Gm system in the susceptibility to IDDM. The analysis does not provide evidence for such an involvement.
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PMID:Two-disease-locus model: segregation analysis using information on two markers in nuclear families. Application to IDDM. 224 83

Antibodies reacting with proinsulin but not with insulin determinants have been observed recently in Type I diabetes. We describe here that ELISA-determined proinsulin autoantibodies (IgG-PAA) also occur in first-degree relatives of IDDM patients (38/513, 7.4% vs 1.9% in controls, P less than 0.025). In contrast to insulin autoantibodies (IgG-IAA) and islet cell antibodies (ICA) no association with HLA type was found. Furthermore, IgG-PAA occur independently of IgG-IAA and ICA. We conclude that the humoral autoimmune response to proinsulin determinants is under separate genetic control.
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PMID:Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLA-DR type. 225 25

We investigated the HLA status of patients with diabetes associated with limited joint mobility and microvascular complications. An increased frequency of HLA-B8, DR3 and DR4 in patients with insulin dependent diabetes mellitus (IDDM) compared to controls and patients with noninsulin dependent diabetes mellitus (NIDDM) was confirmed. HLA antigen DQw1 was detected less frequently in patients with IDDM and was negatively associated with limited joint mobility and retinopathy. Limited joint mobility was significantly correlated with disease duration in IDDM, and was associated with neuropathy in both IDDM and NIDDM and with retinopathy in IDDM. No correlation was found between DR3, DR4 and limited joint mobility or diabetic complications. We also investigated the usefulness of nailfold capillary microscopy in a large group of patients with IDDM and NIDDM. Although capillary enlargement and avascular areas were noted in a few patients, nailfold capillary microscopy was not felt to be a useful tool in the evaluation of diabetes.
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PMID:HLA antigens and nailfold capillary microscopy studies in patients with insulin dependent and noninsulin dependent diabetes mellitus and limited joint mobility. 225 97


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