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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In view of the reported variation in the association between HLA antigens and Juvenile Diabetes Mellitus (J.D.M.) among different Caucasian populations, we have undertaken a study of these antigens among 44 Caucasian Newfoundlanders and 135 matched controls. We have also studied the allotypic markers for Immunoglobulin G (Gm) and variants of C3 among 36 of these patients. We found that both HLA--B8 and B15 were increased among the patient group, resulting in a relative risk of 3.9 and 4.4 respectively. While these values are the highest to be described for J.D.M. among Caucasians, and fell outside the 95% confidence intervals for the combined relative risk calculated from published series, it is still possible that they can be accounted for by sampling. The combination of the two antigens increased the relative risk for J.D.M. in an additive fashion. Additionally, we also found that the combination of HLA B8 and B18, but not B15 and B18, also appear to act in an additive manner. The incidence of Gm allotypes and variants of C3 were not different in the J.D.M. group from those observed among controls.
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PMID:The association of HLA with juvenile diabetes mellitus in Newfoundland. 8 20

Islet-cell antibodies were detected in 11 of the 67 patients with juvenile diabetes mellitus. These antibodies reacted with all endocrine-islet cells, although higher serum dilutions and different staining intensity of the various islet cells were noted. Antibody formation to islet antigens was found to be closely associated with HLA B8 (P = 0.03). However, there was no relationship between islet-cell antibody production and insulin antibody formation. The demonstration of pancreatic islet-cell antibodies, particularly in HLA B8-positive juvenile diabetics, constitutes further circumstantial evidence of a genetically determined auto-immune pathogenesis in some patients with juvenile diabetes mellitus.
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PMID:[Islet-cell antibodies in juvenile diabetes mellitus (author's transl)]. 33 98

Insulin-dependent diabetes mellitus, in contrast to non-insulin-dependent diabetes mellitus, is associated with HLA factors B8, BW15, and B18. Recent studies have shown the association to be even stronger with HLA, DW3, and DW4 and have produced evidence for the existence of two "diabetogenic" genes predisposing to insulin-dependent diabetes in different ways. Evidence to suggest the existence of a gene--associated with DW2--that protects against the disease is accumulating. Islet cell antibodies are a feature of insulin-dependent diabetes mellitus and can be seen, in most cases, at the time of diagnosis.
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PMID:HLA, islet cell antibodies, and types of diabetes mellitus. 34 16

A simple procedure designed specifically to detect linkage for rare recessive diseases is described. The method uses information on identity by descent scores for a pair of sibs at a marker locus conditioned on the number of affected sibs in the pair. A procedure for estimating the recombination fraction is described, and a table facilitating the likelihood ratio test of linkage is provided. The method, when applied to a collection of multiplex families segregating for juvenile diabetes mellitus, suggests the possibility that this disease is linked to the HLA complex. The method is found to compare favorably to the maximum likelihood approach, for which the computer program LIPED gives a maximum lod score of 2.48 at a male and female recombination fraction of theta = 0.20.
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PMID:A simple method to detect linkage for rare recessive diseases: an application to juvenile diabetes. 36 41

Analysis of 100 patients receiving HLA identical sibling transplants was performed. Excellent graft survival demonstrated in the group attests to the importance of matching serological determined antigens. There seems to be a modest beneficial effect on antilymphoblast globulin in low dosage, but not in high doses. Insulin dependent diabetes mellitus results in a significant negative influence on patient survival and graft function in the male recipient but not in the female. A particularly striking point that emerges is the potential hazard in incorrectly treating for rejection. Rejection occurs very rarely in these patients; in a patient with deteriorating renal function, etiologies other than rejection should be vigorously sought (including transcutaneous biopsy) prior to initiation of rejection therapy.
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PMID:100 HLA-identical sibling transplants. Prognostic factors other than histocompatibility. 37 56

HLA antigens were determined in 169 Australian patients with insulin dependent diabetes mellitus (IDDM). HLA-B8 (47.9% v. 23.8%) and B15 (18.9% v. 8.2%) were significantly more frequent in the IDDM patients than in 1460 controls. The relative risks for developing IDDM in people carrying these antigens were 2.94 and 2.59 respectively. Carriers of the B8/B15 genotype had a relative risk of 5.48. These HLA associations in Australian IDDM patients are similar to those reported in other predominantly Caucasian populations.
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PMID:HLA patterns in Australian patients with insulin dependent diabetes mellitus (IDDM). 39 35

Insulin dependent (IDD) and non-insulin dependent diabetes (NIDD) are separate disorders. Twin studies show that IDD cannot be entirely due to genetic causes as concordance is no more than about 50%, but there is some inherited predisposition to it as shown by HLA patterns. NIDD, on the other hand, is predominantly due to genetic causes since identical twins are nearly always concordant. Many cases of NIDD show chlorpropamide alcohol flushing (CPAF), a dominantly inherited feature which may precede the appearance of diabetes and thus act as a genetic marker for this type of diabetes. Diabetics who show chlorpropamide acohol flushing are less likely to develop retinopathy than those who do not. Genetic factors must therefore affect the incidence and severity of diabetic retinopathy. Chlorpropamide alcohol flushing is due to sensitivity to enkephalin. Enkephalin and other opioids affect carbohydrate metabolism and insulin release. It is possible therefore that they act as neurotransmitters and cause NIDD by a sympathetically mediated effect on the liver and pancreas--in other words, that as far as NIDD is concerned Claude Bernard's views on the cause of diabetes may have been right.
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PMID:Diabetes: the genetic connections. 39

An analysis of HLA-linked genetical factors conferring susceptibility to IDDM is reported. On the basis of population and family studies a recessive mode of inheritance of disease susceptibility provided by an assumption of HLA-B8-linked DS gene was observed. The characteristic component of the immunogenetical background was the high frequency of HLA-B8 (0.208) and the HLA-A1, B8 haplotype (0.134) (linkage disequilibrium D = 0.1031), reminiscent of that found also in other disorders with autoimmune features, such as Graves disease, SLE, etc. Considering the HLA-B8 and IDDM association, the DS gene frequency (pD = 0.25) was estimated and the gametic association between HLA-B8 andu DS gene was calculated. The low value of penetrancy (4.8%) revealed the important role of non-HLA-linked genetical and environmental factors. The HLA-linked genetic factors in question might be responsible for an inclination to several kinds of autoimmune disorders.
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PMID:Calculation of disease susceptibility gene frequency in insulin-dependent diabetes mellitus. 39 39

The transmission behavior of insulin-dependent juvenile diabetes mellitus (JDM) has been studied with respect to its frequency in the relatives of JDM probands and its possible linkage to the HLA complex. Mathematical analysis shows that under a single locus hypothesis a very restricted range of incidence rates is possible in the full siblings of probands once the concordance rate in monozygotic (MZ) twins is specified. Specifically, for a given population prevalence of the disease, high concordance rates in MZ twins require high incidence rates in siblings, and low rates require low incidence rates, if a single locus model is th be valid. Moreover, if these rates do conform to a single locus model, then they give additional information about possible linkage between the purported JDM susceptibility gene and the HLA complex. By using observations on the identity by descent scores at the HLA locus of sibling pairs, both of whom are affected with JDM, it is shown that tight linkage of a disease susceptibility locus is possible only when the MZ twin and sibling incidence rates are low, whereas high rates support loose linkage. If the single locus model is rejected, then an alternative hypothesis, involving epistasis between a JDM susceptibility locus and genes in (or close to) the HLA complex can be suggested as a mechanism whereby JDM would appear to be linked to HLA within families while maintaining an association with HLA at the population level.
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PMID:Is juvenile diabetes determined by a single gene closely linked to HLA? 44 10

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.
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PMID:HLA-D--related (DRw) antigens in juvenile diabetes mellitus. 44 15


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