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

Thirty-four insulin-dependent diabetics with a coexistent organ-specific autoimmune disease (Graves' disease, primary myxedema, adrenal insufficiency, generalized vitiligo, primary biliary cirrhosis) were compared to 100 insulin-dependent patients in whom no obvious etiology was detectable. The autoimmune group was characterized by a predominance of females, a family history of autoimmune disease, a later age at onset, better glycemic control, low insulin requirement, persistence of ICA, and greater frequency of HLA B8 but not of B18. However, there was a large overlap between the two groups for all these criteria. In addition, a family history of IDD in first degree relatives and the frequency of serum positive for neutralizing anti-Coxsackie B antibodies were identical in the two groups. These results do not justify the separation of this group of patients as having purely autoimmune diabetes, to the exclusion of other etiological factors, whether genetic or viral.
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PMID:Clinical characteristics and etiological markers in insulin-dependent diabetes associated with an organ-specific autoimmune disease. 631 21

Much clinical and experimental data is in support of a significant role played by viruses in the etiology of diabetes mellitus. This hypothesis is borne out by the association of diabetes mellitus with Coxsackie B, mumps, rubella and herpes simplex virus infections, the presence of high persistent titers of neutralizing antibodies in diabetic patients, the in vitro permissiveness of human beta cells to viruses, and the recovery of viruses from the pancreas of diabetic patients. Viral multiplication is facilitated in HLA B8, B15, B18, Dw3 and Dw4 carriers. Experimental inoculation of EMC and Coxsackie B viruses to mice shows that beta cell involvement is dependent upon viral strains, viral membrane receptors, interferon production, immunological response and less essential factors such as age and sex. The virus is responsible for a specific immunological response and produces autoimmunological phenomena. These result in a decrease in the number and activity of insulin-producing cells through cytotoxic mechanisms. Pathological findings corroborate these physiopathological hypotheses.
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PMID:[Viruses and juvenile diabetes mellitus]. 632 9

The frequency of HLA antigens incidence with due consideration for diabetes type and age of the patient by the disease onset was studied and the index of the relative risk of diabetes development was calculated. In patients with type I diabetes mellitus, a significant increase of B18 antigen incidence and decrease of B7 antigen incidence were observed, as compared to the controls. No association with HLA antigens were detected in type II diabetes. No differences in HLA antigen incidence in type I diabetes mellitus patients who fell ill before 30 and those who fell ill after 30 years of age were recorded. The index of relative risk of the disease development in patients with type I diabetes is higher in the presence of B18 and lower in the presence of B7 antigens.
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PMID:[The HLA system in diabetes mellitus]. 633 52

Present knowledge regarding the HLA system and the association between HLA antigens and insulin-dependent type 1 diabetes mellitus (IDDM) is reviewed. The heterogeneity of diabetes, immunogenetically speaking, is emphasized. Results are reported for HLA typing in 18 cases of known IDDM recently diagnosed and observed at the Karen Bruni Diabetes Center in approximately one year (1981-82). The frequency of HLA antigens B7, B8 (in linkage disequilibrium with DR3), B15 (in linkage disequilibrium with DR4) and B18 was examined in comparison with a Piemontese control group. The X2 method was used for calculating the relative risk and statistic importance of the intensity of association. IDDM susceptibility in association with HLA-B18 was confirmed and resulted significantly higher in our cases in respect to controls. Correlations without, however, reliable importance, have also been found between HLA-B8 and B15. IDDM protection by HLA-B7 was not confirmed. Diabetes began during the winter, from October to February, in 10 out of 18 cases, and some were positively related to a previous respiratory viral infection. Previous virus infection was found in three B7-positive cases. The more frequent arousal of diabetic symptoms during the winter in subjects positive for HLA-B8 and B18 was confirmed in 7 out of 8 cases. This work demonstrates the current practicability of HLA typing of recently diagnosed insulin-dependent diabetic in a Diabetes Center. This element helps to a more correct classification--on a subclinical basis--of initial cases of type 1 and 2 diabetes and can be used for possible problems during the course of insulin therapy.
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PMID:[The HLA system and insulin-dependent diabetes mellitus. A review and personal studies]. 638 59

The typing of 22 HLA-A and B antigens in members of 13 families with one child having juvenile diabetes mellitus showed a statistically significant higher frequency of HLA-B8 antigen in sick children (51.54%) as well as high parental heredity rate of this antigen, as compared to 301 normal subjects and 51 normal children of families free from diabetes mellitus. The agreement of 85.71% in one or two haplotypes in diabetic and healthy siblings in 7 families involved antigens other than B8. The results of these family studies confirm the existing relationship between HLA-B8 and juvenile diabetes mellitus as demonstrated by repeated screenings of the patients populations. The relationship of HLA antigens to insulin-dependent juvenile diabetes mellitus has been studied by many authors. The issues of their studies on patient populations revealed HLA-DR3, Dw3, DR4, Dw4, B8, B18, B15, B40, Cw3 and secondarily A1 and A2 to occur with significantly higher frequency. On the other hand, antigens DR2, Dw2, B7 (secondarily A3 and A11) are statistically less frequent in this disease, and their presence therefore means a certain protection against the risk of diabetes (4, 6, 7, 11, 15, 21). Individual authors' family studies differ in conclusions as to the occurrence of some of the above HLA antigens, and the degree of HLA identity of two siblings, one with diabetes, the other one normal (6, 8, 12, 17). For this reason we decided to start investigations on the occurrence of HLA A and B antigens in family members with one child having juvenile diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA and insulin-dependent juvenile diabetes mellitus. 641 92

The literature of the past ten years shows that the introduction of highly purified heterologous and, lastly, homologous insulins has notably lowered the production of IgG and IgE specific insulin antibodies, but has not succeeded in completely eliminating clinical manifestations of the immune or hyper-immune response to insulin therapy. In particular, insulin allergy with or without lipodystrophy is still seen. Among the factors of insulin immunogenicity, there is a possible genetic control of the immune response in type I diabetes: determining HLA halloantigens (A, B, C, D) might identify specific immune response genes (Ir genes). Initial researches, performed until now almost exclusively upon diabetics treated with conventional heterologous insulin, seem to indicate a positive relationship between haplotype HLA - B15 - DR4 and an elevated immune response, whereas haplotypes HLA - B8 - DR3 and HLA - B18 - DR3 might protect against the formation of anti-insulin antibodies. Antigens D/DR3 and D/DR4 are known to be primitively associated to susceptibility for type I diabetes, whereas antigens B8, B15, B18 are secondarily associated to the rise in frequency of DR3 and DR4 for the "linkage disequilibrium" existing between alleles of B and D loci. The results of HLA typing are presented in 2 groups of insulin-dependent diabetics (ID) followed from an immunological viewpoint during therapy with monocomponent heterologous insulin for over 5 years. The first group is composed of 50 patients with low IgG anti-insulin antibody titers (less than 1 mU/ml, Christiansen: low responders); the second group is made up of 23 patients with high IgG anti-insulin antibody titers (greater than 2.5 mU/ml, Christiansen: high responders) and includes 5 subjects with insulin allergy (associated or not with insulin lipoatrophy) and high levels of insulin specific IgE antibodies. A study of the frequencies of various HLA-B antigens in both groups of patients, in regard to a control group of piemontese population, in relation to the intensity of association (relative risk) and to the statistical importance of frequencies, shows only a possible protective effect of the HLA-B18 phenotype (linkage disequilibrium with HLA - DR3) towards the production of anti-insulin antibodies and hyperimmune clinical manifestations, such as allergy. Reliable conclusions are not possible between low and high responders for the other phenotypes (HLA - B7, B8, B15) commonly implicated. HLA-B12 was noted in 3 of 5 patients with allergy, in 2 cases associated with B8.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[HLA typing and insulin antibody production in insulin-dependent diabetics]. 644 4

Patients with Graves' disease were phenotyped for properdin factor B (Bf) and glyoxalase, which are coded for by genes mapping close to the HLA region on the sixth chromosome. Frequency data were analysed in relation to HLA-A, -B and -DR typing data. Diagnosis of Graves' disease was based on the usual criteria including elevated T3 and T4 levels and free T4 index and a homogeneous thyroid scan. Ninety-four patients with Graves' disease were phenotyped for properdin factor B (Bf) and 37 for red cells glyoxalase (GLO). HLA-A, -B and -DR antigens were typed in 94 patients using a lymphocyte microcytotoxicity assay. The frequency distribution of Bf and GLO alleles showed no significant differences from control subjects. This finding contrasts with the reports of an increased frequency of BfF1 in insulin-dependent diabetes mellitus. The difference in the two diseases which are both associated with an increased frequency of the antigen combination D8-DR3, is accounted for by linkage disequilibrium between B18 and BfF1.
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PMID:Properdin factor B (Bf) and glyoxalase in Graves' disease. 657 32

This report deals with the genetic factors involved in insulin-dependent diabetes mellitus (IDD) in The Netherlands. Twenty-two Dutch multiplex families with IDD were typed for HLA-A, -B, -C, and -DR antigens, for BF, C2, C4, and GLO polymorphisms, as well as for GM allotypes of immunoglobulins. In addition, 53 unrelated IDD children and 31 unrelated patients with adult onset IDD were typed for HLA-A, -B, -C, and -DR antigens. A significant heterogeneity for the frequency of HLA-DR4 related to age of onset was observed. A significant deviation of the Hardy-Weinberg equilibrium was observed for the HLA-DR locus with an excess in patients of heterozygotes HLA-DR3, -DR4.HLA-B8, and HLA-B15 were not only secondary associated, but constituted with HLA-DR3 and -DR4, respectively, a haplotype in association with IDD. Nonrandom segregation of HLA-haplotypes was observed in multiplex families exemplified by an excess of HLA-identical affected sibpairs . Cross- overs between HLA-DR and GLO identified the HLA-DR segment as mainly involved in the association with IDD. Three diabetic haplotypes were confirmed to occur frequently among affected sibs: (a) A1, B8, BFS, C2.1, C4AQO , C4B1 ,DR3, GLO2 ; (b) Aw30, Cw5 ,B18,BFF1,C2.1, C4A3 , C4BQO ,DR3, GLO2 ; (c) A2,Cw3, B15,BFS, C2.1, C4A3 , C4B3 , DR4,GLO1. The segregation of GM allotypes to affected sibpairs was not significantly different from random segregation. The main conclusions from this study are that significant heterogeneity for age of onset exists and that the data are not compatible with simple genetic models including dominant, recessive, and intermediate models of inheritance. The data do require more complex models, involving two different HLA-linked (sets of) susceptibility genes.
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PMID:HLA and GM in insulin-dependent diabetes in the Netherlands: report on a combined multiplex family and population study. 658 8

Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.
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PMID:Genetic heterogeneity of insulin-dependent (type I) diabetes mellitus: evidence from a study of extended haplotypes. 659 40

One hundred and thirty-three insulin-dependent diabetic (IDD) patients were genotyped for HLA-A, B, C, DR and 123 of them for Bf. The study shows a relationship between these genes and the age of onset of diabetes and emphasizes the possible heterogeneity of the disease. When patients under the age of 0 years at the onset of the disease were compared with those aged 11 to 29 years, a significant excess of HLA-B18 (41% versus 15%, p less than 0.001) and BfF1 (40% versus 21%, P less than 0.05) was observed. The haplotype B18, BfF1 was also more frequent in the first group of patients (haplotype frequency 18% versus 6%, p less than 0.02). The frequency of the whole haplotype Cw5, B18, BfF1, DR3 and of its segment BfF1, DR3, and the strength of the gametic associations between these alleles were much higher in IDD patients than in non-diabetic controls, irrespective of the age of onset of their diabetes. The association between early age of onset of IDD and the B18, BfF1 haplotype independently of DR3 (no association between age and DR3) suggests that a factor influencing the onset of the disease in young children could be under the control of (1) gene (s) in linkage disequilibrium with B18 and/or BfF1.
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PMID:Age--related heterogeneity of insulin-dependent diabetes mellitus. 660 51


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