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

We studied the distribution of HLA-D--related (DRw) antigens in 40 patients with juvenile diabetes mellitus (JDM) and 79 matched controls. We found that DRw2 was significantly decreased in the JDM group, suggesting a protective effect of the antigen and that the decrease observed in B7 was secondary. HLA-DRw3 and HLA-DRw4 were increased in the diabetic group, and, as with B8/B15, these two antigen predisposed to the disease additively. The susceptibility for JDM was found to be more strongly related to HLA-DRw3 that to B8. On the other hand, B15 rather than DRw4 showed the stronger association with JDM. Moreover, we found that this second diabetogenic gene is associated primarily with B15 and only secondarily with Cw3, which is in linkage disequilibrium with B15. This study further emphasizes the immunogenetic heterogeneity of JDM.
Diabetes 1979 Jun
PMID:HLA-D--related (DRw) antigens in juvenile diabetes mellitus. 44 15

Data are collected here that may support the hypothesis that there is an infectious component in the genesis of insulin-dependent diabetes mellitus. The clinical and experimental data on which that hypothesis is based referring to viruses such as: mumps virus, rubella virus, encephalomyocarditis virus, and Coxsackie B viruses, are presented. The authors mention the pathogenic mechanism, which extends over the existence of diabetogenic genes linked to the major complex of the histocompatibility HLA system, as well as the existence of an autoimmune reaction induced by the infecting virus. This review shows up the large gaps that exist in the accurate knowledge we have about the possible infectious etiology of diabetes. However, it also offers different pathogenic possibilities for further experimental investigations on bases that are reasonably scientifically consistent.
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PMID:[Viral etiology of insulin-dependent diabetes (author's transl)]. 45 6

The distribution of phenotypes controlled by two loci on chromosome 6 has been studied in a series of 239 patients with type 1 (insulin-dependent) and 297 patients with type 2 (non-insulin-dependent) diabetes mellitus. At the properdin factor B (Bf) locus there is a significant increase in the frequency of the BfSu and BfF1 alleles for type 1 patients, and the combined inc;rease in frequency of BfS1 and BfF1 in those patients is highly significant. The relative risk for F1 is 6.2 and for F1 and S1 combined is 5.3. These results confirm the association with F1 reported recently by Raum and co-workers in Boston. The two rare alleles BfS1 and BfF1 are in significant negative disequilibrium with HLA B8. For the glyoxalase (GLO) locus there is a slight but nonsignificant increase in the frequency of the GLO2 allele, but a significant disturbance in the distribution of the GLO phenotypes for type 2 patients. These results for the GLO alleles may be due to stratification in our series of type 2 patients. Further studies are in progress to test this hypothesis.
Diabetes 1979 Oct
PMID:Genetic susceptibility to diabetes mellitus: the distribution of properdin factor B (Bf) and glyoxalase (GLO) phenotypes. 47 86

To study the association of histocompatibility (HLA) genes in black persons with juvenile-onset diabetes, we determined HLA-A, HLA-B, HLA-C and HLA-DR specificities in 40 black Americans with this disease and in 67 unaffected black Americans. Marked increases in the frequencies of HLA-DRw3 and HLA-DRw4 were found in the patients as compared with the unaffected persons: DRw3 was found in 72.5 per cent of patients versus 29.9 per cent of unaffected persons and DRw4 in 72.5 per cent versus 25.4 per cent (corrected P values each less than 0.0007). DRw2 was not found in any of the patients but was present in 26.9 per cent of unaffected persons (P corrected less than 0.035). There is thus a negative correlation between this specificity and juvenile-onset diabetes. By contrast, no meaningful differences were found in the frequencies of A, B, or C locus antigens. Studies in white persons with juvenile-onset diabetes have suggested that the reported HLA-B associations are due to HLA-D region specificities, and our results also support the premise that D region specificities are the primary associations with juvenile-onset diabetes.
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PMID:HLA-DR specificities among black Americans with juvenile-onset diabetes. 48 12

The study was designed to show whether there was any relation between muscle capillary basement membrane thickness, HLA-antigens, anti-insulin antibodies and proliferative retinopathy. Electron microscopic measurements of muscle capillary basement membrane thickness were performed on muscle biopsies from 15 insulin-dependent diabetics and severe proliferative retinopathy, 24 insulin-dependent diabetics with minimal retinopathy and 18 age- and sex matched non-diabetics. All the patients had had diabetes for 20 years or more. None had biochemical or clinical evidence of diabetic nephropathy. Basement membrane thickness was measured according to the methods of Siperstein and Williamson. Muscle capillary basement membrane thickening occurred in 32 of 39 diabetics, using the Siperstein method, but patients with proliferative retinopathy did not exhibit thicker basement membranes than patients with no or minimal changes in the retina. There were apparent differences in HLA-antigens between diabetics with and without proliferative retinopathy, but they did not reach statistical significance. There was no correlation between muscle capillary basement membrane thickness and the quantity of insulin antibodies. The results indicate that factors other than basement membrane thickening and genetic factors in the HLA-region, are responsible for the development of proliferative retinopathy.
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PMID:Basement membrane thickness, insulin antibodies and HLA-antigens in long standing insulin dependent diabetics with and without severe retinopathy. 48 71

The studies of HLA in diabetes mellitus have strongly supported the subdivision into (at least) two genetically distinct groups: The juvenile onset (or perhaps better the insulin dependent) type DM, which shows a marked association to the HLA system, and the maturity onset type with a weak or no association to HLA. The HLA system has provided tools to test specific genetic models for the insulin dependent DM. A model involving one disease susceptibility locus closely linked to the HLA-loci and with a recessive susceptibility allele in linkage disequilibrium with some of the HLA factors has been proposed by others. This model cannot be totally rejected on the basis of the available data, but it is made less likely, especially because it leads to very low estimates of the penetrance which is discrepant from independent estimates, based both on studies on monozygotic twins and other families. In addition suggestive but not yet conclusive evidence of an excessive risk for HLA-Dw3/Dw4 heterozygotes is in conflict with this model.
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PMID:HLA studies in diabetics. 49 95

We have briefly discussed immunogenetic studies of families with hyperglycemia which suggest the existence of at least four types of the disease: a) juvenile, insulin-dependent, ketosis prone diabetes determined by an autosomal recessive gene with 50% penetrance and in linkage with the HLA; b) juvenile, insulin-dependent, ketosis prone diabetes probably determined by an autosomal dominant gene; c) unidentified types of juvenile, insulin-dependent diabetes whose pathogenesis may be related to the HLA associations reported; and d) maturity onset type of hyperglycemia in the young, probably determined by an autosomal dominant gene. There are probably other forms of juvenile hyperglycemia. Some may depend on genes unrelated to the HLA, others may be mostly or totally environmental, rather than genetic.
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PMID:On the genetic heterogeneity of juvenile hyperglycemia. 49

The relationship between the HLA system and insulin-dependent diabetes mellitus (IDDM) is reviewed. Data compiled by the HLA and Disease Registry reveal that HLA-B8 and/or Dw3 are associated with IDDM in all populations studied so far, but further population studies in non-Caucasian populations should be performed. In Caucasians, HLA-Dw2 renders protection against IDDM while HLA-Dw3 and Dw4 are associated with susceptibility to IDDM. The exact mode of inheritance of susceptibility to IDDM remains to be established. Involvement of at least two genes is likely. Heterogeneity of IDDM is highly possible and should be a matter of major interest in diabetes research.
Diabetes Care
PMID:Studies of the HLA system and insulin-dependent diabetes mellitus. 52 Jan 25

Regardless of the well-documented population associations between juvenile-onset diabetes (JOD) and certain HLA types, whatever haplotypes are segregating in JOD families may be followed to provide information on mode of inheritance of the disorder. It is essential to group together for analysis families with the same number of affected sibs. We assume a single locus determining susceptibility, closely linked to the HLA region, and ignore recombination, expected to be rare. Our first approach also assumes that the frequency of the susceptible genotype is so small that affected individuals may be considered to arise from only one mating type; the particular mating type depends on the mode of inheritance of susceptibility. Our sample is the result of pooling our own data with published studies of HLA haplotype segregation in families with two or more JOD offspring. Given the assumptions, we find that the data are more plausibly explained by a one-dose than by a two-dose or "recessive" hypothesis. We then develop the analysis further by adding a crude but explicit estimate of the frequency of the susceptible genotype, based on disease prevalence and penetrance of the genotype. The one-dose hypothesis is strongly supported by this analysis as well. We also consider some problems of ascertainment arising from heterogeneity of the disorder and selection against diabetics. Studies involving unaffected relatives of diabetics are suggested which might test further the conclusions drawn here.
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PMID:Inheritance of susceptibility to juvenile onset diabetes. 52 86

Population studies in Israel have shown that Jews born in Europe or America have the highest prevalence of juvenile diabetes mellitus and Jews born in Asia or Africa, the lowest. The rate in the Israel born, regardless of the father's place of birth, is intermediate between those of the other two groups. The rates for the group from Europe/American and for the Israel-born group increased during the years 1963-68, while that for the Asia/Africa group did not change. It is speculated that the differences in the rates of juvenile diabetes mellitus are related to different frequencies of certain HLA antigens in the different groups or to different associations with susceptibility genes to juvenile diabetes.
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PMID:Juvenile diabetes mellitus. 52 82


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