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)

Initial reports of blood T cell subsets in insulin-dependent (type I) diabetes mellitus (IDDM) are conflicting and, consequently, difficult to relate to animal models of the disease. To minimize technical artefacts, which may have contributed to previous results, we used direct immunofluorescence on whole blood and counted 3,000 lymphocytes by flow cytometer. Forty-two IDDM patients divided in three groups of 14 according to the disease duration and 12 age and sex matched controls were studied for T3, T4, T8 and HLA-DR expression. No statistically significant differences were found in their total blood lymphocyte counts or in the percentage of T3, T4 and T8 positive cells, although mild lymphopenia was found in the group of long-standing diabetics. The percentage of activated T cells, identified as T3+/DR+ cells, was significantly increased in the groups of patients studied more than a month after diagnosis and in four of 14 patients studied within a month from diagnosis. Seven new onset IDDM patients were studied for co-expression of T8 and Leu 15 antigens (putative suppressor cell phenotype), but no significant differences was found compared with controls. We conclude that T4/T8 ratio abnormalities previously reported in Ficoll separated cells are not reproduced when unseparated cells are analysed by flow cytometry, although the presence of HLA-DR+ T cells is confirmed.
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PMID:T-lymphocyte subpopulations in insulin-dependent (type I) diabetes mellitus. 293 83

During the fall of 1979, 22/250 Swedish UN soldiers serving in Egypt were hospitalized with fever and gastroenteritis associated with aseptic meningitis. One of the 22 developed insulin dependent diabetes mellitus (IDDM) 10 weeks following the infection. The majority of the 22 patients showed significant titer rise for coxsackievirus B by plaque reduction neutralization test. The serology results indicate that coxsackievirus B4 most likely caused the outbreak. All 22 were also tested for islet cell cytoplasmic antibodies and islet cell surface antibodies and found negative. The individual developing diabetes mellitus had the HLA-DR phenotype 3,4, which is associated with IDDM.
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PMID:An outbreak of coxsackievirus B infection followed by one case of diabetes mellitus. 298 80

Mumps epidemics are followed by sporadic cases of insulin dependent diabetes mellitus (IDDM). We have studied beta-cell function in 11 subjects who had had a mumps infection. They had no clinical pancreatitis but were selected as they had abnormal pancreas iso-amylase values and/or glucosuria during the mumps virus infection. At the follow-up some years later the subjects were healthy. A few HbA1-values were noted in the upper part of the normal range. Total serum insulin values were normal, but the C-peptide values were low at first follow-up 1-3 years after infection in all but two patients. These values increased in 4/7 patients during the follow-up period but were subnormal in five subjects still 3-6 years after the infection. All five patients had HLA-DR 3 and/or 4. In 7 out of 11 patients islet cell surface antibodies could be demonstrated. Our results indicate that subclinical mumps pancreatitis may initiate a reaction towards the beta-cells recognized as subnormal C-peptide levels several years later in certain patients. This might contribute to manifest IDDM many years after infection.
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PMID:Mumps with laboratory signs of subclinical pancreatitis may cause a disturbed beta-cell function. 307 6

Associations of insulin dependent diabetes mellitus exist with the HLA-DR antigens DR3 and DR4 in both British Caucasoid and Dravidian subjects. However, it is only in British Caucasoids that an increased relative risk is found in those subjects who co-inherit both of these antigens. The nature of these HLA associations has been explored using Southern blot techniques and radioactive HLA-D region probes. In both populations the same DR4 related polymorphism was found in IDDM subjects whereas different HLA-DR3 preferential allelic associations were observed between British Caucasoid and Dravidian subjects. The best differentiation between diabetics and controls was found by a combination of HLA-DQ region alpha and beta polymorphisms which were totally different for the two populations. These data indicate that at least one gene involved in the susceptibility to IDDM is located within the HLA-DQ region and this may be related to HLA-DR4. The location of a DR3 related gene remains elusive and may be the DR beta gene encoding DR3 itself. In both populations it is a combination of two HLA-D region haplotypes which is strongly associated with IDDM leading to the possibility of trans complementation leading to the formation of mixed isotypic dimers.
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PMID:The genetic susceptibility to IDDM in British and south Indian subjects. 314 91

After the death of a 12-year old girl with newly discovered insulin-dependent diabetes mellitus, we used monoclonal antibodies in an effort to identify the cells invading the pancreas. The majority of infiltrating lymphocytes were of the T cytotoxic/suppressor phenotype, but other T-cell subpopulations were present. Some of the T cells were "activated" (positive for HLA-DR antigen, and the interleukin-2 receptor). Immunocytes bearing IgG were scattered in the gland, and complement-fixing IgG antibodies were deposited in some islets. Increased expression of Class I (HLA-A, B, and C) molecules was observed in the affected islet cells, and in damaged islets showing scant lymphocytic infiltration, some beta cells (still producing insulin), but not glucagon or somatostatin cells, were HLA-DR positive. The capillary endothelium was markedly dilated and strongly HLA-DR positive. These findings may contribute to an understanding of the sequence of events leading to the destruction of beta cells in classic Type I diabetes mellitus.
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PMID:In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. 315 65

In a pilot study, on a hospital-based series consisting of 285 type 1 and 282 type 2 patients with Diabetes Mellitus (DM) we compared the month-of-birth with the standard birth curve. In accordance with a previous investigation on 23,620 diabetics in the Netherlands, we found an excess of DM births in the first quarter of the year (p less than 0.005) and a deficiency of them during the last one. This excess corresponds with conceptions during the spring restoration of the ovulatory pattern, this deficiency with conceptions during its winter stabilization. Identical peaks and troughs have been found in month-of-birth studies of individuals with chromosomal anomalies and with anencephaly. Similarly, ovopathy--which we consider a common cause for multiple anomalies--can explain the high incidence of DM in Down's syndrome as well as in other chromosomal aberrations, and its association with unusual dermatoglyphics. Furthermore, the ovopathy concept appears in line with the consistently found maternal age and parity effect, the discordancy in one-egg twins and the distortion of HLA-DR phenotype distribution in IDDM multiplex families. Although our conclusions must be guarded because of sample bias and doubts concerning precise classification, we found that the configurations were stronger in the type 2 DM sample. Ovopathy might prove to be the crucial environmental factor in the causation of IDDM--searched for by many scholars--and a common cause for both types. The HLA-DR haplotypes might rather be the "trigger", influencing the course and type of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Month-of-birth distribution of diabetics and ovopathy: a new aetiological view. 324 28

The reasons for the presence of activated T-lymphocytes (ATL) in some long-standing insulin-dependent diabetic (IDDM) patients are unknown. These cells have been implicated in the genesis of proteinuria in some forms of immune-mediated renal disease. We measured ATL in 18 IDDM patients with diabetic nephropathy, 10 with nonnephrotic proteinuria (total urinary protein excretion rate greater than 0.5 and less than 3.5 g/24 h) and 8 with nephrotic proteinuria (total urinary protein excretion rate greater than 3.5 g/24 h), and in 17 age-, sex-, and duration-of-diabetes-matched diabetic control subjects without clinical proteinuria (total urinary protein less than 0.5 g/24 h). T-lymphocytes purified from peripheral blood were stained by direct immunofluorescence with the fluorescein-labeled monoclonal antibody anti-HLA-DR. Absolute number and percent of DR-positive T-lymphocytes were significantly higher in patients with nonnephrotic proteinuria (median and range 162 x 10(6)/ml, 40-320 x 10(6)/ml; 13.9%, 8.1-19.4%) compared with nonproteinuric control subjects (81 x 10(6)/ml, 2-240 x 10(6)/ml, P less than .05; 6.2%, 0-13.1%, P less than .01). In 8 patients with nephrotic proteinuria, absolute and percent DR-positive T-lymphocytes tended to be lower (36 x 10(6)/ml, 14-56 x 10(6)/ml; 3.4%, 1.1-5.4%) than in nonproteinuric control subjects. An increased number of activated T-lymphocytes may be part of an immune-mediated process associated with the development of proteinuria in diabetic nephropathy. In advanced renal disease with nephrotic proteinuria, this immune process may become exhausted.
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PMID:Proteinuria and activated T-lymphocytes in diabetic nephropathy. 325 34

To assess the immunologic differences related to histocompatibility leukocyte antigen (HLA) haplotypes in patients with type 1 diabetes, trivalent killed influenza virus vaccine was given in the fall, when no influenza occurred, to 59 patients with diabetes (mean age 16 years) and 64 siblings without diabetes (mean age 36 years). All subjects had normal hemagglutination inhibition antibody responses at days 14 and 42 after vaccination, with no significant differences noted between patients with diabetes and those without diabetes. However, subjects with HLA haplotypes DR 3, DR 4, or both had lower antibody responses to influenza A/Chile and B/USSR at 14 days after vaccination (p less than 0.02) than DR x/x controls (who lacked 3 or 4). Lymphocyte transformation (LT) responses before and after vaccination were similar for patients with diabetes and those without diabetes. Of significance was that subjects with HLA haplotypes DR 3, DR 4, or both had 41.1% LT responders at 42 days after vaccination, compared with subjects with HLA-DR x/x (lacking 3 or 4) who had 22.6% responders (p less than 0.03), when influenza A/Chile was used as an antigen. Although not significant, influenza antigens A/Philippines and B/USSR each showed similar trends with increased postvaccine LT responses. The HLA associations were independent of sex, age, and the presence of diabetes. These studies suggest that HLA haplotypes DR 3 and DR 4, which were clearly linked to type 1 diabetes mellitus, were also associated with altered immune responsiveness to influenza viral proteins.
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PMID:Immune responses to killed influenza vaccine in patients with type 1 diabetes: altered responses associated with HLA-DR 3 and DR 4. 326 55

Study of two diseases with autoimmune characteristics (IDDM and SLE) has demonstrated that alleles carried in the MHC can confer disease susceptibility. The MHC alleles most strongly associated with the development of IDDM are encoded within the class II region (HLA-DR or -DQ). Recent studies indicating that the class III gene products TNF alpha and beta may play a critical role in the initiation of the autoimmune attack on the pancreatic beta-cells have suggested the possibility that the class III region may also contribute to genetic susceptibility in IDDM. In SLE, although there is some evidence suggesting that certain alleles of class II genes may confer disease risk, a more striking association has been detected in the class III region. Deficiency of the class III encoded C4A molecule (either homozygously or heterozygously) shows a high correlation with disease risk. This finding is attractive because C4A plays a central role in the metabolism of immune complexes, the aberrant deposition of which leads to the most prominent alterations in SLE.
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PMID:The major histocompatibility complex and autoimmunity. 332 10

To investigate the possible coinheritance of autoimmune diseases that are associated with the same HLA antigen, we studied 70 families in which at least two siblings had either type I diabetes mellitus (IDDM), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), or a combination of these diseases. HLA-A, B, and C typing was performed on all affected sibs in one generation or more. First, we estimated by sib-pair analysis the disease allele frequency (pD) and the mode of inheritance for each disease. According to the method of ascertainment entered into the analysis, the pD for ATD ranged from .120 to .180, for an additive (dominant) mode of inheritance. For RA, the pD ranged from .254 to .341, also for additive inheritance, although recessive inheritance could not be excluded. For IDDM, the pD ranged from .336 to .337 for recessive inheritance; additive inheritance was rejected. Second, we examined the distribution of shared parental haplotypes in pairs of siblings that were discordant for their autoimmune diseases. The results suggested that the same haplotype may predispose to both IDDM and ATD, or IDDM and RA, but not to both RA and ATD. Analysis of pedigrees supported this hypothesis. In 16 families typed for HLA-DR also, the haplotype predisposing to both IDDM and ATD was assigned from pedigree information to DR3 (44%), DR4 (39%), or DR5, DR6, or DR7 (5.5% each). In some families, these haplotypes segregated over several generations with ATD only (either clinical or subclinical), suggesting that in such families, ATD was a marker for a susceptibility to IDDM. In several families, an IDDM haplotype segregated with RA but not with ATD. This suggests that ATD- and RA-associated susceptibilities to IDDM may be biologically different and thus independently increase the risk of IDDM.
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PMID:Genetic interrelationship between insulin-dependent diabetes mellitus, the autoimmune thyroid diseases, and rheumatoid arthritis. 345 97


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