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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of our study was to evaluate what kind of relationships exist between HLA antigens and insulin-dependent diabetes mellitus (IDDM), in 20 families and in 40 single patients coming from and living in North Eastern Italy. The subjects studied show a strong association with HLA-DR3 and/or -DR4; at least one of these antigens is present in 88% of the diabetic subjects; this confirms that these antigens play a role in the pathogenesis of IDDM. We also noticed a negative association between IDDM and DR5 rather than DR2 and DR7. This result supports the hypothesis of a specific protective effect of DR5, at least as regards the population studied. Possibly, the gene(s) hypothetically involved in the protection against IDDM is (are) in linkage disequilibrium with DR2 and/or DR7 in some Caucasian populations and with DR5 in others. Another important result is the frequent HLA identity (75% of cases) among diabetic siblings of the same families. This result indicates that HLA identity is the main condition responsible for the susceptibility to the disease in the healthy siblings with HLA antigens identical to the diabetic siblings.
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PMID:HLA gene and phenotype data of 60 insulin-dependent diabetic patients from north-eastern Italy. A negative association with DR5 rather than DR2? 207 85

Fifteen women with positive islet cell antibodies were identified in a group of 115 consecutive patients found to have impaired glucose tolerance in pregnancy. These subjects were postulated to be at increased risk of later developing type 1 diabetes mellitus. They were examined post--partum for HLA types known to be associated with this disease and for any increase in Interleukin 2 receptor expression or alteration of T cell subsets of possible relevance to its pathogenesis. Fifteen women negative for islet antibodies and with normal glucose tolerance during previous pregnancy and 15 women with a normal fasting plasma glucose who had never been pregnant were studied as controls. Using flow cytometric techniques a significant increase in both the number and proportion of activated (Interleukin 2 receptor, CD25) lymphocytes in the peripheral blood of women who had islet cell antibodies and previous impaired glucose tolerance in pregnancy was found (0.14 +/- SE 0.03 x 10(9)/l; 7.1 +/- 1.1%) when compared with normal parous controls (0.09 +/- 0.01 x 10(9)/l; 4.2 +/- 0.6%), p less than 0.01 x 10(9)/l; showed significant increases when compared with nulliparous controls (0.04 +/- 0.01 x 10(9)/l; 2.1 +/- 0.2%), p less than 0.01. No differences were detected between the three groups with respect to total T-lymphocytes (CD3), helper T-lymphocytes (CD4), suppressor cytotoxic T-lymphocytes (CD8), or the inducer of suppressor (Leu 3+/Leu 8+) subset of T-lymphocytes. Three women persistently islet cell antibody positive, two of whom were HLA DR4, showed impaired glucose tolerance at the time of lymphocyte subset analysis, while two further patients, one DR3 and the other DR4, had developed type 1 (insulin-dependent) diabetes. No correlation between increased Interleukin 2 receptor expression and glucose intolerance was demonstrated. We conclude that islet cell antibody positive women with impaired glucose tolerance during pregnancy are at increased risk of later developing type 1 diabetes but that heightened immune activation present in these women is in part a post-pregnancy phenomenon.
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PMID:Increased interleukin 2 receptor expression in post-gestational women: relationship to impaired glucose tolerance and islet cell antibodies in pregnancy. 210 86

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

Juvenile insulin-dependent diabetes mellitus develops in susceptible children exposed to unknown environmental factors. If the genes responsible for susceptibility could be identified, it should be possible to understand the method of injury to beta cells as well as identify the infectious or other agents involved. For a decade it has been known that one or more of the susceptibility genes must be within the major histocompatibility complex (MHC). Unfortunately, there are at least 20 different genes in the complex and it has not been possible to determine which are actually responsible. Therefore, we undertook to apply a new concept and new technology to the problem. Over several years we have shown that the diabetogenic gene(s) are contained within conserved ancestral haplotypes which can then be used as markers of the DNA which must contain the gene(s), whether present in a patient or an asymptomatic carrier such as a parent. This approach avoids the confusion which has resulted from using DR3 or DR4 which are only sometimes associated with the relevant genes. The new technology involves pulsed field gel electrophoresis which allows examination of large fragments of DNA containing all of the MHC, and makes it possible to identify deletions and duplications which were otherwise undetectable. In the first instance we compared two ancestral haplotypes [1,8,3 (8.1) and 18,F1,3 (18.2)] known to contain the relevant genes, and contrasted the DNA with that of another ancestral haplotype [3,7,2(7.1)] which is known to lack these genes. We have shown that there are three major deletions common to the two carrier haplotypes but absent in the protective haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Supratypes and ancestral haplotypes in IDDM: potential importance of central non-HLA MHC genes. 218 61

Urinary albumin excretion (UAE) was determined by radioimmunoassay in two 24 h urine collections from 125 diabetic children and adolescents and from 71 normal children matched for age and sex. Thirteen patients (10.4%) aged greater than 12 years had microalbuminuria, i.e. log transformed UAE levels above the upper normal range (24.5 mg/24 h). UAE values were positively correlated with age, GH secretion, but not with duration of disease, glycosylated hemoglobin, renal size or N-acetyl-beta-glucosaminidase excretion. Diabetic normoalbuminuric children aged 10 years and older had significantly higher UAE than controls and than younger diabetic patients matched for duration of disease. HLA DR3/DR4 heterozygosity frequency was significantly higher (p less than 0.01) in the microalbuminuric group than in the normoalbuminuric. All microalbuminuric subjects (n = 8) with short duration of disease (3.92 +/- 3.43 yr) developed diabetes at puberty. In conclusion, our cross-sectional study suggests: if a number of factors are combined, i.e. HLA DR3/DR4 heterozygosity, onset of disease at puberty and higher GH values, the probability of developing abnormal levels of UAE will increase.
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PMID:Microalbuminuria in diabetic children and adolescents. Relationship with puberty and growth hormone. 219 Apr 42

Notable progress was achieved by the investigations on the immunology of diabetes. Studies of immunogenetics have demonstrated that Type 1 (insulin-dependent) diabetes shows a primary association with the HLA class II genes (e.g., with HLA-DR3 and DR4 in Caucasoid populations), a determining features of this type of the disease. Besides, it presents a wide variety of autoantibodies, such as islet-cell cytoplasmic antibodies (ICA), islet-cell surface antibodies (ICSA), complement-fixing islet-cell antibodies (CF-ICA), antibodies to a Mr-64000 islet-cell protein, and many studies are trying to evaluate their pathogenic and predictive role. Various changes of cell-mediated immunity have been also described. The proportion of activated T cells in circulation is increased in patients with Type 1 diabetes. It was assumed that the T cells are the main cause of pancreatic beta-cell damage. Type 1 diabetes is actually considered as a chronic autoimmune disease, with several stages of evolution leading to the destruction of the pancreatic beta-cells, with a consecutive gradual decrease of insulin secretion. From the therapeutic point of view, many problems are raised by insulin immunogenicity, mainly depending on the so-called "contaminants". To avoid phenomena of allergic reactions, immunological insulin-resistance, lipodistrophy, a.o., highly purified and human type insulins have been prepared. The insulin autoantibodies (IAA) detected before the clinical onset of Type 1 diabetes are considered a new marker of autoimmunity. New hopeful prospects are opened by diabetes immunotherapy, in which Cyclosporin A detains a particular role, although it should be used only in special conditions, under strict clinical observation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunological aspects of diabetes. 219 11

A total of 15 families were investigated: probands with insulin-dependent diabetes mellitus and their relatives of the 1st degree of progeny (43 persons) in order to study the distribution of HLA antigens and their interrelationship with the gravity of a course of diabetes mellitus and the type of GTT. Antigens DR3 and/or DR4 were revealed in 93% of probands, especially in heterozygous patients (57.1%). A low level of C-peptide (0.21 +/- 0.03 ng/ml) was noted in most of the probands excluding 3 patients with nephropathy. Distinct relationship of antigens DR3 and DR4 with a clinical course of disease and its severity was undetectable. Antigens DR3 or/and DR4 were detected in 96% of the relatives with the prevalence of antigen DR4 (in 54.2%). During GTT normal tolerance was observed in 82.1% (23 persons), disorders were noted in 4, insulin-dependent diabetes mellitus--in one. Most of the relatives (82.6%) with normal glucose tolerance had antigens DR3 and/or DR4. Irrespective of the type of DR antigens the probands' relatives were characterized by moderate hyperinsulinism (by the results of IRI and C-peptide of blood serum).
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PMID:[An analysis of the interrelationship of the HLA genotype and carbohydrate metabolism in the families of probands with insulin-dependent diabetes mellitus]. 220 51

The analysis of HLA-DQ beta nucleotide sequence polymorphism in insulin-dependent diabetes mellitus (IDDM) patients and control subjects suggests a role for the DQ beta-chain in genetic susceptibility. Sequence determination and oligonucleotide hybridization was carried out on enzymatically amplified DNA from various HLA-DR-typed individuals, including the rare class of DR2+ patients. In the analysis of DQ beta variation in DR4, DRw6, and DR2 haplotypes, a correlation was observed between the presence of the negatively charged residue Asp at position 57 and low susceptibility and the presence of an Ala (DR4), Val (DRw6), or Ser (DR2) and higher susceptibility. However, important exceptions to this pattern have been identified in the analysis of heterozygous DR1/4 IDDM patients. In these individuals, susceptibility appears to correlate with specific DR beta l alleles (Dw4) on the DR4 haplotype, rather than with the DQ beta allele (DQB3.2) that contains Ala at position 57. The DQ beta alleles found in some Chinese IDDM patients also proved discordant with the position-57 correlations. Thus, although there is a general correlation between the residue at position 57 of the DQ beta-chain and IDDM susceptibility, these data do not support the notion that Asp 57 confers complete resistance or protection to IDDM. In general, these results suggest that IDDM susceptibility is conferred by specific combinations of DQ beta and DR beta sequences.
Diabetes 1990 Jan
PMID:HLA-DQ beta sequence polymorphism and genetic susceptibility to IDDM. 221 66

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

Type 1 diabetes is associated with extended haplotypes defined by combinations of specific alleles of genes in the MHC. We have used pulsed field gel electrophoresis mapping to examine the gross structure of the Class II region of the MHC and its relationship to susceptibility to Type 1 diabetes. We have studied heterozygous members of a family in which susceptibility to Type 1 diabetes is associated with an A1/B8/DR3 haplotype and resistance with A2/B7/DR2, an unrelated diabetic DR3,4 patient and a healthy DR4,w10 subject and a DR2/Dw2 cell line. Digestion was performed with the enzymes Sst II, Mlu I, and Pvu I and hybridization with 21-hydroxylase, DRA, DQB, DOB and DPA probes. Within the DQ/DR region the DR4- and DR7-bearing haplotypes studied contain insertions of 140-150kb relative to the DR3 haplotypes whilst the DR2 haplotype in the family was smaller than the DR3 haplotypes by 130kb, whilst that in the cell line was smaller by up to 220kb. This cell line, previously thought to be homozygous by consanguinity, was also shown to be heterozygous in the DP region. Although no differences between diabetic and healthy subjects were observed within the family, these differences in long-range structure may be of importance to the etiology of Type 1 diabetes, as well as to the evolution of the MHC.
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PMID:Large haplotype-specific differences in inter-genic distances in human MHC shown by pulsed field electrophoresis mapping of healthy and type 1 diabetic subjects. 224 84


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