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

As suggested from clinical data and on the basis of human leukocyte antigen (HLA) data, insulin-dependent diabetes mellitus (IDDM) is a disease entity in itself and is different from non-insulin-dependent diabetes and other types of diabetes mellitus in aetiology and pathogenesis. HLA-B8 is associated with IDDM in all Caucasian populations studied, irrespective of the age of onset of the disease. HLA-B15 is associated with IDDM in populations of Northern European and British origin, while B18 seems to replace B15 in Southern European populations. IDDM is uncommon in populations where the HLA-B8 frequency is low, and in the Japanese IDDM occurs in association with Bw22. The HLA-Dw3 and Dw4 association with IDDM is stronger than that of the B alleles. Relative risks for B8 and B15 heterozygous and homozygous individuals are identical, i.e., no gene-dose effect exists. The relative risk of B8/B15 carriers is double that of relative risks of B8 and B15 alone, i.e., there are two IDDM-associated genes. The same applies to Dw3/Dw4 carriers. In families the phenotype IDDM segregates with a certain genotype, the diabetic proband's HLA haplotype. Only a small proportion of family members carrying the 'diabetic haplotype' develop IDDM.
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PMID:HLA and insulin-dependent diabetes mellitus. 11 82

We studied a human leukocyte antigen-identical pancreas graft transplanted into an insulin-dependent (type I) diabetic patient shortly after onset of recurrent diabetes to characterize the putative autoreactive T lymphocytes mediating the lesion. The immunohistopathological analysis revealed the presence of isletitis and a selective loss of beta-cells. The isletitis was mostly constituted by CD8+/T-lymphocyte receptor alpha,beta (TCR alpha,beta +) T lymphocytes surrounding and infiltrating the affected islets. CD4-/CD8-/TCR gamma, delta + T lymphocytes were observed within the islets. Incubation of the tissue in 15% interleukin 2 induced the migration and initial expansion of the infiltrating cells (66% CD3+ lymphocytes) for up to 2 wk; most T lymphocytes in this initial isolate were CD4+ (92% CD4+ and 7% CD8+). Long-term anti-CD3 stimulation of this T-lymphocyte population induced the selective growth of CD8+/TCR alpha,beta + (75%) and CD4-/CD8-/TCR gamma,delta + (all V1 delta +) (17%) T lymphocytes. Therefore, this strategy selectively expanded the T lymphocytes, found to be the predominantly islet-infiltrating cells, rather than the lymphocytes predominating in the initial isolate. Anti-CD3 did not stimulate growth of T lymphocytes in cultures of three isletitis-free pancreas graft biopsies. In a control experiment with a CD4(+)-rich T-lymphocyte population, long-term anti-CD3 stimulation and cloning of cytomegalovirus (CMV)-primed peripheral blood mononuclear cells from a CMV+ subject selectively induced the growth of CD4+ T-lymphocyte clones, all CMV specific.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Jan
PMID:Characterization of T lymphocytes infiltrating human pancreas allograft affected by isletitis and recurrent diabetes. 130 55

The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody-negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies may be relatively common, it progresses only in those with variant HLA-DQ molecules.
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PMID:Autoimmunity and genetics contribute to the risk of insulin-dependent diabetes mellitus in families: islet cell antibodies and HLA DQ heterodimers. 823 77

A significant proportion of relatives of patients with insulin-dependent (type I) diabetes with high titers of cytoplasmic islet cell autoantibodies (ICAs) do not progress to overt diabetes with up to 8 yr of follow-up. This may reflect that follow-up of such relatives has not been long enough to observe diabetes, that despite expression of identical ICAs, some relatives will not progress to diabetes; or that there is heterogeneity in what is identified as ICA. We identified a subset of ICA that was restricted in its species (not reacting with mouse islets) and cell-type reactivity within islets (beta-cell specific). Only one of eight relatives whose sera had the restricted pattern of reactivity progressed to overt diabetes, and on sequential evaluation, all but the one relative who progressed to diabetes have maintained normal first-phase insulin secretion to intravenous glucose. In contrast, by life-table analysis, 70% of relatives expressing nonrestricted ICA became diabetic within 5 yr of follow-up (1 of 8 vs. 16 of 25 diabetic at last follow-up, P less than 0.02). Moreover, preliminary data suggest a significant association of the human leukocyte antigen DQB1*0602 allele of DR2 haplotypes with the restricted ICA pattern (4 of 5 DQB1*0602 restricted vs. 0 nonrestricted ICA, P = 0.006). We propose that expression of a genetically determined restricted ICA pattern confers a markedly lower risk for progression to diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Mar
PMID:Prognostically significant heterogeneity of cytoplasmic islet cell antibodies in relatives of patients with type I diabetes. 155 94

While the human leukocyte antigen (HLA) region provides the major susceptibility for insulin-dependent (type I) diabetes mellitus (IDDM), other (non-HLA) genes must also play a role. Population studies have shown an increased frequency of small insertions (class I alleles) 5' to the insulin gene in individuals with IDDM, suggesting that this region may account for part, if not all, of the non-HLA genetic predisposition. However, no data are available as to whether the relation of the insulin gene polymorphism is to a DR-defined subset of IDDM or with all of IDDM. To test the hypothesis that specific combinations of HLA and insulin gene polymorphism alleles may interact in providing susceptibility for IDDM, HLA-DR and 5' insulin gene insertion size have been determined in 300 individuals with IDDM. The frequency of class 1 insulin gene alleles in the entire sample is 0.79 and the frequency of class 3 alleles (large inserts) is 0.20. The frequencies of class 1 alleles were equal across all DR classes: 0.79 in the DR3/X IDDM subjects, 0.80 in the DR4/X, 0.79 in the DR3/4, and 0.78 in those with DRX/X. Additionally, the frequencies of class 1/1 homozygotes and 1/3 heterozygotes were similar between HLA-DR types. These results suggest that the HLA region and the region 5' to the insulin gene provide independent and nonsynergistic genetic risks for IDDM.
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PMID:HLA-DR and the 5' insulin gene polymorphism in insulin-dependent diabetes. 196 Nov 15

Research in recent years has elucidated more clearly the genetic and immunopathogenic basis as well as the natural history of Type 1 diabetes mellitus. The development of Type 1 diabetes can be conceptually divided into stages, beginning in part with a human leukocyte antigen (HLA)-restricted genetic susceptibility. In some genetically susceptible subjects, a triggering event activates both cellular and humoral autoimmunity. Glucose-stimulated insulin secretion and beta cell mass diminish as anti-islet autoimmunity progresses. This process culminates in overt diabetes when only residual beta cell mass (estimated to be less than 10%) remains. Complete beta cell destruction follows within months to years of diagnosis. Most attempts at interrupting beta cell destruction have taken the form of broad immunosuppressive therapy begun at diagnosis when beta cell destruction is nearly complete. Greater understanding of early immune mediators and refinement of techniques to identify subjects at risk for Type 1 diabetes have set the stage for more specific immunomodulation targeted earlier in the course of the disease. We will review these recent advances in understanding the immunopathogenesis of Type 1 diabetes as they pertain to current and future trials of immunotherapy.
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PMID:Immunopathogenesis and immunotherapy of type 1 diabetes. 218 47

Characteristics of a multiplex sample of families with insulin-dependent diabetes mellitus (IDDM) are studied and contrasted with similar characteristics in other, more conventionally sampled data sets. Some characteristics remain consistent with earlier observations including the high frequency of human leukocyte antigen (HLA) DR3,4 in affected individuals and the greater than expected percentage of HLA haplotype sharing among affected sib pairs. In other respects, however, differences are seen between this sample and others. "Control" haplotypes, i.e., those not transmitted to the first affected offspring, had a higher frequency of DR3 and DR4 than expected, and a rather high frequency of affected parents was observed. Differences between the first affected and later affected offspring reported in other samples were absent from these families. No effect of the sampling scheme and the resulting distribution of parental phenotypes could be shown to explain this difference.
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PMID:Characteristics of a multiplex IDDM sample: unexplained differences with other samples. 249 6

The allelic forms of the human leukocyte antigen (HLA)-DQ beta-chain (DQB1) have been recognized as the best markers of insulin-dependent diabetes mellitus (IDDM) susceptibility. We describe a method that allows the recognition of these DQB1 alleles without the use of either allele-specific oligonucleotide probes or radioactive material. This method determines these alleles by electrophoretically separating restriction enzyme-generated fragments from the polymerase chain-reaction-amplified second exon of the HLA-DQB1 gene, which encodes the first domain of the protein chain. This digestion method, which is simpler and more rapid than the previously adopted hybridization method, is described in detail to enable individuals at any clinical laboratory to quickly ascertain IDDM susceptibility.
Diabetes 1989 Dec
PMID:Rapid detection of IDDM susceptibility with HLA-DQ beta-alleles as markers. 258 80

This study was undertaken to investigate the impact of diabetes, which develops after heart transplantation, on infection and patient survival. Nondiabetic patients (366) underwent heart transplantation at our institution between June 1, 1980 and January 12, 1988. Of these patients, 29 (8%) developed posttransplantation diabetes (PTD), defined as a continued need for hypoglycemic agents. The PTD group did not differ significantly from the nondiabetic recipients in age, sex, or human leukocyte antigen type. The average age in the PTD group was 49 years. Average length of follow-up was 21 months (range 4 to 46 months). Eighteen patients are maintained on insulin. Eight patients are on oral hypoglycemic agents. Three patients died while on insulin. The average prednisone dosage in this group is 0.23 mg/kg/day. There have been 18 minor infections and four potentially serious nonlethal infections in the 27 PTD recipients. One lethal infection occurred 33 months after heart transplantation. The only other fatality was related to metastatic bladder cancer. This lethal infection rate of 3% compares with a rate of 11% in all nondiabetic recipients who have follow-up for 21 months. The 3-year actuarial survival of the PTD group is 75%, which compares favorably with the survival of nondiabetic patients. PTD cannot be predicted by sex, age, or human leukocyte type before transplantation, and it does not significantly increase the incidence of mortality or serious infection.
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PMID:Posttransplantation diabetes mellitus in heart transplant recipients. 265 24

The initial course of Type 1 (insulin-dependent) diabetes mellitus was studied in two groups of Japanese children, i.e. 21 patients with abrupt onset (Group A) and 19 patients detected by urine glucose screening at school with minimal or no symptoms (Group B). There was no statistical difference in mean age at diagnosis between Group A and B (11 +/- 3 years vs 11 +/- 3 years). Group A patients revealed a rapid deterioration of pancreatic B-cell function, but there was evident recovery of the B-cell function from 3 to 9 months following initial treatment. The B-cell capacity in Group B was self maintained until 24 months after diagnosis. Thereafter, even these patients exhibited a progressive decline in the B-cell function. The two groups had a similar incidence of islet cell antibodies at diagnosis (58% vs 69%). However, human leukocyte antigen studies revealed that patients in Group A had a significantly higher prevalence of DR4 and DRW9 than those in Group B (p less than 0.01). These results suggest that in Japanese children there are two forms of diabetes, an abrupt and a slow onset form, which are clinically different and which also seemed to be genetically independent types, or possibly the same disease diagnosed at different stages.
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PMID:Type 1 (insulin-dependent) diabetes in Japanese children is not a uniform disease. 266 18


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