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

Thirty Ethiopian malnutrition-related diabetes mellitus (MRDM) patients were HLA typed and their HLA antigen frequencies were compared to those of 31 previously typed insulin-dependent diabetes mellitus (IDDM) patients and to 84 controls from the same ethnic background. In comparison to controls, a striking association between MRDM and HLA-DR3 (X2 = 15.15, p = 0.0001) was observed, whereas the frequency of HLA-DR4 was non-significantly increased (RR = 1.72). The frequency of DR2, DQw1, and DQw6 was decreased among MRDM. In comparison to IDDM that is associated with both DR3 and DR4 in this population, MRDM showed no significant differences in HLA class II antigens frequencies. Therefore, the genetic basis of susceptibility to MRDM and IDMM in Ethiopia is at least partially identical.
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PMID:HLA-DR and -DQ antigens in malnutrition-related diabetes mellitus in Ethiopians: a clue to its etiology? 262 60

The incidence rate of insulin-dependent (Type I) diabetes mellitus is bimodal: one peak occurs close to puberty, and the other in the fifth decade. To evaluate possible differences in these forms of the disease, we examined the clinical, biochemical, autoimmune, and genetic features of 82 children and adolescents (1.3 to 18.2 years old) and 44 adults (20.0 to 55.8 years old) when they presented with Type I diabetes. The mean (+/- SEM) duration of symptoms before diagnosis was longer in the adults (7.5 +/- 1.0 vs. 3.9 +/- 0.4 weeks; P less than 0.001), and their serum C-peptide concentrations at diagnosis were higher (0.29 +/- 0.03 vs. 0.17 +/- 0.01 nmol per liter; P less than 0.001), suggesting that they had more residual beta-cell function. There were no significant differences between the two groups in sex ratio, blood glucose levels, hemoglobin A1 values, degree of metabolic decompensation, or frequency of Type I diabetes in first-degree relatives. Thirty-four of 80 children tested (42.5 percent) were positive for insulin autoantibodies, as compared with only 1 of 26 adults (3.8 percent; P less than 0.001). However, the frequencies of islet-cell autoantibodies were similar in the adults and children (conventional autoantibodies, both 81 percent; complement-fixing autoantibodies, 46.2 percent and 60 percent). More children than adults were heterozygous for both HLA-Dw3/4 antigens (26.6 percent vs. 9.8 percent; P less than 0.05) and HLA-DR3/4 antigens (36.6 percent vs. 12.5 percent; P less than 0.05). We conclude that Type I diabetes that begins in adulthood is characterized by a longer symptomatic period before diagnosis, better preservation of residual beta-cell function, and lower frequencies of insulin autoantibodies and HLA-D3/D4 heterozygosity than Type I diabetes that begins in childhood or adolescence.
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PMID:A comparison of childhood and adult type I diabetes mellitus. 264 46

In spite of the potential assay problems, a relatively clear general picture concerning islet cell antibodies has emerged. They are undoubtedly the most potent indicator of risk for insulin-dependent diabetes, at least among high-risk persons (that is, first-degree relatives of insulin-dependent diabetics). Islet cell antibodies have been the focus of intense research scrutiny over the last decade, yet their etiologic role remains unclear. In patients with insulin-dependent diabetes, there is no striking relation at onset between islet cell antibodies and determinants such as age and HLA type. Certain characteristics, however, may be related to islet cell autoimmunity in a more complex way. There appears to be some racial difference in onset-related islet cell antibody prevalence and other autoimmunity. The observation that autoimmune abnormalities are more frequent among women and among diabetics leads to the question of whether there is an interaction of sex and autoimmune diabetes. There may be a group of early-onset patients, distinguished by persistent islet cell antibodies or coexistent autoimmune phenomena, who are predominantly female. At present, there is only limited evidence for this in the literature: Bottazzo et al. found that juvenile diabetics with persistent islet cell antibodies were more often female. Female diabetics have been shown to have an increased prevalence of thyroid autoantibodies compared with male diabetics. Several observations of differences based on sex have emerged from recent studies of insulin-dependent diabetes: 1) the HLA-DR4 antigen is more frequent among female diabetic patients; 2) male HLA-identical siblings of diabetics have a lowered insulin response to glucose administered intravenously; 3) in areas of low insulin-dependent diabetes incidence, the patterns of onset by age differ markedly between the sexes. These sex-specific differences may help to clarify the relation between islet cell autoimmunity and sex. Among nondiabetic persons, those having the highest genetic "risk" for disease appear to have an increased prevalence of islet cell antibodies. There is also some indication that HLA-DR3 may be associated with islet cell autoimmunity. Other related diseases, notably gestational diabetes, non-insulin-dependent diabetes, and certain autoimmune endocrinopathies, are associated with an increased prevalence of islet cell antibodies. An increase in islet cell antibody prevalence occurs in certain viral infections, particularly mumps and congenital rubella. Islet cell antibodies have been noted in the sera of subjects many years before the onset of insulin-dependent diabetes, as well as in normoglycemic relatives.
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PMID:Epidemiology of islet cell antibodies. 268 May 55

Cytokines and their related enzyme pathways may play a part in the development of insulin-dependent diabetes mellitus (IDDM). We have therefore studied the activity of the enzyme 2'-5' oligoadenylate synthetase (which is induced by both interferon and the tumour necrosis factors) in circulating mononuclear cells from 40 subjects with IDDM and 32 healthy control subjects. There was no difference in mean basal enzyme activity between the two groups. A polymorphism of the 2'-5' oligoadenylate synthetase gene, not previously described, was found using the restriction enzyme Bam HI. There was no association of 2'-5' oligoadenylate synthetase genotypes with IDDM, but there was a significant correlation between basal 2'-5' oligoadenylate synthetase activity and 2'-5' oligoadenylate synthetase genotypes. Significantly higher mean basal levels of 2'-5' oligoadenylate synthetase activity were associated with HLA-DQA 4.6 phenotype (determined using the restriction enzyme Taq 1 and a DQA probe) and HLA-DR3 (determined serologically), whereas significantly lower mean levels of enzyme activity were associated with HLA-DQA 5.5 and HLA-DR7, in both IDDM and control subjects. An analysis of variance confirmed that these associations were independent 2'-5' oligoadenylate synthetase genotype. Likewise, a significantly higher mean level of enzyme activity was associated with the heterozygous 1/3 insulin-related genotype in the IDDM subjects only. This study therefore suggests that the possession of certain HLA haplotypes might be associated with differing levels of basal 2'-5' oligoadenylate synthetase activity.
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PMID:2'-5' oligoadenylate synthetase and its relationship to HLA and genetic markers of insulin-dependent diabetes mellitus. 268 62

The multiplex insulin-dependent diabetes mellitus (IDDM) families have been examined for linkage with the human leukocyte antigen (HLA), Gm, Km, and insulin loci. For the last three, no evidence of linkage (as measured by haplotype sharing in affected siblings) was found. For HLA, strong evidence of linkage was demonstrated, as expected from previous studies of both haplotype sharing and HLA association. The haplotype sharing in affected siblings from this and previous studies would explain a relative risk of about 3.7 in the sibling of an affected individual (95% confidence limits 2.8 to 5.4), considerably less than the values of 10-15 given by epidemiological studies. This discrepancy may be explained by other predisposing genes unlinked to HLA, or be due to common environmental factors. Analysis conditional on the affection status of all individuals, and on the parental HLA haplotypes clearly rejects both a dominant and recessive mode of inheritance in favor of a two-allele model with a reduced risk for heterozygotes, and provides some support for a three-allele model. Some evidence of age effects was found; in particular there was some suggestion of greater haplotype sharing in siblings both affected at a young age, and there was some suggestion that individuals with the predisposing HLA-DR3/DR4, DR3/DRx, and DR4/DRx genotypes were affected at a younger age. These results may be diagnostic artifacts, however, and need investigation in future studies.
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PMID:Linkage analysis and genetic models for IDDM. 273 21

The study of HLA histocompatibility antigens and insulin-dependent diabetes mellitus (IDDM) in non-White populations may provide a unique opportunity to more accurately define the diabetes susceptibility gene(s) located within the HLA region. To determine whether HLA haplotypes differ between ethnic groups, we compared 105 HLA haplotypes from 55 Mexican-American IDDM patients with 272 haplotypes from 136 IDDM patients of non-Hispanic White descent. The accurate determination of genotypes and haplotypes requires the study of family units. Therefore, all diabetic patients in this study were from studies of families having one or more siblings with IDDM. In the Mexican-American group, HLA-DR3 and -DR4 were the most common HLA-DR alleles and were present in comparable frequencies in the non-Hispanic White group (HLA-DR3, 27% of Mexican-American and 29% of non-Hispanic White haplotypes; DR4, 46% of Mexican-American and 43% of non-Hispanic White haplotypes). However, the HLA-B/DR-containing haplotypes and haplotype frequencies differed between the two groups. Several common haplotypes (B8/DR3, B15/DR4) in the non-Hispanic White group occurred less frequently in the Mexican-American group. In contrast, uncommon haplotypes in the non-Hispanic White group comprised nearly 50% of the DR4-containing haplotypes (B35/DR4, B40/DR4, B44/DR4) in the Mexican-American group. Although both DR3- and DR4-haplotype frequencies differed significantly between the two groups, the relative frequency of DR3- but not DR4-containing haplotypes was similar in both ethnic groups. This adds to the evidence suggesting that different susceptibilities are provided by the haplotypes carrying the DR3 and DR4 alleles.
Diabetes Care
PMID:Different HLA haplotypes in Mexican Americans with IDDM. 275 54

Insulin autoantibodies (IAAs) are associated with type I diabetes mellitus (DM) and have been suggested as predictive markers of the disease. Using an ELISA assay, we have studied the prevalence of binding to human insulin in sera from an Arab type I DM population and compared it with the prevalence in the family members (FMs) of the probands, in type II DM patients from the same population, and in Arab control subjects. Significant levels of binding occurred in 11/16 (69%) of type I DM patients and in 21/34 (62%) of their FMs, but in only 5/31 (16%) of type II DM patients and in 1/25 (4%) of control subjects. Within families, there was homogeneity with regard to the level of insulin binding and the mean family levels correlated with those of the proband (r = 0.68, df = 7, p = 0.05). HLA-DR3 or -DR4 antigens occurred in 55/63 (87%) of type I DM patients and in 95/118 (81%) of their FMs. This was significantly higher (p less than 0.001) than in either type II DM patients (39/75, 52%) or in control subjects (34/93, 37%). ICAs were present in significantly more (25/43, 58%) of type I DM patients than their FMs (3/82, 3%) (p less than 0.001). They did not occur in either type II DM patients or in the control group. In conclusion, insulin binding occurred in sera from both type I diabetic patients and their kindred, and hence did not appear to be specifically associated with the development of clinical diabetes.
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PMID:Insulin binding substances, autoimmunity and type I diabetes in Kuwaiti patients and their kindred. 278 62

We studied interleukin 1 (IL-1) and interleukin 2 (IL-2) production in unstimulated and stimulated cultures from 27 young diabetic patients and 21 age-matched healthy subjects. In unstimulated cultures monocytes from newly diagnosed patients produced significantly higher levels of IL-1 than controls. In lipopolysaccharide (LPS)-stimulated cultures, IL-1 production in patients with fresh and long-standing diabetes was no different from that of controls. IL-2 production was low or absent in unstimulated cultures from insulin-dependent diabetes mellitus (IDDM) patients and controls. In phytohaemagglutinin (PHA)-stimulated cultures both patient groups produced significantly less IL-2 than controls. No correlation was observed between IL-1, IL-2 production and HbA1 levels or the presence of HLA-DR3 or DR4. Our data on "spontaneous" IL-1 production support the hypothesis that monocytes from some newly diagnosed IDDM patients may circulate in a "preactivated" state. The low levels of IL-2 might be explained by an abnormal consumption or by the presence of increased soluble IL-2 receptor levels or by a serum factor which interferes with IL-2 production. Alternatively, it may be a genetically determined trait.
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PMID:Alterations of in vitro interleukin 1 and 2 in diabetic children. 279 22

It is well established that there is genetic heterogeneity between a human lymphocyte antigen (HLA)-DR3-associated allele and an HLA-DR4-associated allele in insulin-dependent diabetes mellitus (IDDM). Equally well established are the association of DR3 with Graves' disease and other autoimmune disorders in nondiabetics and the increased prevalence of autoimmune thyroid disease in IDDM. Perhaps in large part because of these facts, it has been postulated that there are two major forms of classical IDDM--one form characterized by coexistent autoimmune disease, such as autoimmune thyroid disease which is associated with DR3, and another form not associated with additional autoimmune disorders, which is associated with DR4. Several studies have repudiated the idea of specific clinical findings in IDDM being associated exclusively with DR4. However, the DR3-thyroid association in IDDM has not been investigated carefully. Therefore, in order to study this putative association, we divided a group of diabetic children into overlapping subgroups based on thyroid enlargement, antithyroid microsomal antibodies, acquired hypothyroidism, and no evidence of thyroid disease. The distributions of HLA-DR3 and -DR4 among these subgroups did not differ from each other; nor did the distribution of the HLA alleles differ from those of randomly selected IDDM individuals. These results suggest that thyroid autoimmunity in IDDM is part of the IDDM "syndrome" and is associated with DR3 and DR4 to the same extent that IDDM without thyroid disease is associated with these two antigens. Thus, although genetic studies are consistent with the heterogeneity between DR3 and DR4 in IDDM, there is no HLA-thyroid disease association to support this heterogeneity.
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PMID:Autoimmune thyroid phenomena are not evidence for human lymphocyte antigen-genetic heterogeneity in insulin-dependent diabetes. 280 76

The HLA-DR3 haplotype is associated with increased risk of myasthenia gravis (MG) and a number of other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), coeliac disease, and premature ovarian failure (POF). With a cDNA probe for a DQ beta gene, a 15 kb Hinc II restriction fragment has been demonstrated in genomic DNA from 7 of 16 HLA-DR3 patients with MG, 1 of 19 healthy DR3 controls, and none of 24 DR3 patients with IDDM, coeliac disease, or POF. The HLA-DQ polymorphism may be closely linked to a genetic locus regulating immune responsiveness to acetylcholine receptor and susceptibility to MG.
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PMID:HLA-DQ beta-chain polymorphism linked to myasthenia gravis. 287 36


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