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

Type 1 diabetes results from the destruction of insulin-producing pancreatic beta cells. Genetic and environmental factors are implicated in the beta cell destruction. As environmental factors affecting the induction of type 1 diabetes, diabetogenic viruses, chemicals, toxins, and diet are likely candidates as either primary injurious agents of beta cells or triggering agents for the induction of autoimmunity. Regarding viruses as a triggering factor of type 1 diabetes, there are at least two different pathogenic mechanisms in virus-induced diabetes: cytolytic infection of beta cells, leading to their destruction, and triggering of autoimmunity, leading to the autoimmune-mediated destruction of beta cells. Since there is no correlation between the induction of antibodies to Coxsackie B viruses and the presence of islet cell autoantibodies in patients with type 1 diabetes, the induction of diabetes by Coxsackie B viruses may be due to cytolytic infection of beta cells rather than an autoimmune response. In contrast, rubella virus and cytomegalovirus (CMV) do appear to be somehow associated with autoimmune type 1 diabetes since there is a strong correlation between the presence of islet cell autoantibodies and persistent infections. Regarding genetic factors, there are distinct markers related to the susceptibility to Coxsackie B4 virus-associated type 1 diabetes and CMV-associated type 1 diabetes. Four specific DNA restriction endonuclease fragments (BamHI-DQ-beta 6.6, TaqI-DR-beta 4.3, TaqI-DR-beta 2.5 and TaqI-DR-beta 1.5 kb) are related to the susceptibility to Coxsackie B4 virus-associated type 1 diabetes while six specific DNA restriction endonuclease fragments (BamHI-DQ-alpha 12.5, -beta 3.7 and -beta 3.2 kb, TaqI-DQ-alpha 7.2, -beta 7.2 and -beta 5.4 kb) are related to the susceptibility to CMV-associated type 1 diabetes.
Diabetes Res Clin Pract 1989
PMID:Viruses as a triggering factor of type 1 diabetes and genetic markers related to the susceptibility to the virus-associated diabetes. 268 Mar 67

DNA from Caucasian normal healthy control subjects, non-gravid patients with insulin-dependent diabetes mellitus (IDDM) and gravida with gestational diabetes mellitus (GDM) were analyzed with DNA probes for HLA markers associated with HLA-DR and HLA-DQ to compare the hybridization patterns of their DNA after digestion with restriction endonucleases. We report HLA-DQ beta restriction endonuclease fragments to be presented with increased frequency in Caucasian gravida with GDM as well as in subjects with IDDM. These findings provide further evidence for genetic heterogeneity in GDM and are compatible with the presence of slowly evolving IDDM in some women with "carbohydrate intolerance of variable severity with onset or first recognition during pregnancy".
Diabetes Res 1987 Nov
PMID:Gestational diabetes mellitus is associated with HLA-DQ beta-chain DNA endonuclease fragments. 283 74

Restriction fragment length polymorphism of the human insulin receptor gene was analyzed with a 4.2 Kb cDNA probe in Japanese normal subjects and Type 2 (non-insulin-dependent) diabetic patients. Restriction endonuclease Rsa I digestion showed polymorphism of the human insulin receptor gene, with a band at 6.7 Kb, 6.2 Kb or 3.6 Kb. The frequency of the 6.7 Kb band was less than that in Caucasians. Furthermore, 15% of all the Japanese subjects examined lacked a 3.6 Kb band, which is commonly found in Caucasians. We have also detected restriction fragment length polymorphism in the human insulin receptor gene by Pvu II or Stu I digestion. Although no significant association of restriction fragment length polymorphism with Type 2 diabetes was found in the present study, our results suggest that the restriction fragment length polymorphism in the human insulin receptor gene varies among ethnic groups, and that the restriction fragment length polymorphism linked to the human insulin receptor gene might be a useful marker for the linkage study of the genes located close to the human insulin receptor gene on chromosome 19.
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PMID:Restriction fragment length polymorphism (RFLP) of the human insulin receptor gene in Japanese: its possible usefulness as a genetic marker. 287 50

The hypervariable region 5' to the human insulin gene has been characterised in two South African Indian families, each having two generations of individuals affected with non-insulin-dependent diabetes mellitus (NIDDM). Southern blot analysis, with the restriction endonuclease Pvu II and plasmid phins 310 as a probe, was used. In family 1, class 1 alleles (0.87, 0.79, 0.72 and 0.68 kilobase (kb)) were found at this locus but no linkage with NIDDM was shown. In family 2 a class 3 (2.51 kb) and two class 1 alleles (0.89, 0.76) were found. The 0.89 kb allele appears to be segregating with NIDDM in this family.
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PMID:Non-insulin-dependent diabetes mellitus and the 5' hypervariable region of the insulin gene in two South African Indian families. 288 Apr 1

A DNA sequence polymorphism, revealed by digestion of genomic DNA with the endonuclease Xba1 and hybridisation with a complementary DNA clone for a human glucose transporter, yields two alleles (sizes 6.2 kbp, the X1 allele; or 5.9 kbp, the X2 allele). The genotype frequencies were investigated in three non-insulin-dependent diabetic populations. The frequencies (%) of X1.X1, X1.X2, and X2.X2 were 13, 51, and 36 among 89 North European diabetic subjects, and 8, 38, 54 among their 104 controls (chi 2 test p less than 0.02; G-test p less than 0.02). For 53 South European diabetic patients the frequencies were 19, 50, 31, and for their 41 controls they were 2, 58, 40 (chi 2 test p less than 0.02; G-test p less than 0.01). The corresponding figures were 6, 55, 39 for 45 Japanese patients and 0, 28, 72 for a further 49 controls (chi 2 test p less than 0.01; G-test p less than 0.001). The occurrence of the association of the X1 allele with diabetes in three separate populations suggests that the polymorphic site may be close to a diabetogenic locus on chromosome 1.
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PMID:Association of genetic variant of the glucose transporter with non-insulin-dependent diabetes mellitus. 289 75

In order to ascertain whether the immunoglobulin heavy chain genes are important in the aetiology of Type 1 diabetes, we have used restriction fragment length polymorphism (RFLP) analysis of genomic DNA to study 148 Caucasoid subjects with Type 1 diabetes and 146 normal Caucasoid subjects. A DNA probe homologous to the switch regions for the IgM (S mu) and IgA1 (S alpha 1) genes when used in conjunction with the restriction endonuclease Sst I detects RFLPs at both these loci. There were no significant differences in phenotype or gene frequencies for the alleles of S mu or S alpha 1 in the patients when compared with control subjects; nor were there significant associations of S mu or S alpha 1 with HLA-DR type or gender.
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PMID:Immunoglobulin heavy chain switch region polymorphisms are not associated with type 1 diabetes. 290 16

Genotypes identified by two restriction fragment length polymorphisms (RFLPs) of the insulin receptor gene (IRG) with the restriction endonuclease Sst-1 were determined in a Japanese group comprising 51 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 50 control subjects. Southern hybridization using a probe for the beta subunit of the human IRG identifies 4 alleles, termed S1(+) (5.3 kb), S1(-) (5.8 kb), S2(+) (7.0 and 2.4 kb) and S2(-) (9.4 kb). The frequencies of genotypes possessing the S1(-) allele in Japanese controls and Japanese NIDDM patients were 0.11 and 0.16, respectively. Unlike the previously reported association of the S1(-) allele with NIDDM found in Caucasians there was no significant difference in the frequency of the S1(-) allele between non-diabetic and NIDDM Japanese patients. There was a significant difference in the frequency of the S2(+) allele between Caucasian control subjects (0.14) and Japanese controls (0.0) and NIDDM patients (0.02).
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PMID:DNA polymorphisms of the insulin receptor gene in Japanese subjects with non-insulin-dependent diabetes mellitus. 290 2

Polymorphic restriction endonuclease sites within the HLA-DR alpha gene have been defined, localized, and used as genetic markers in the analysis of susceptibility to insulin-dependent diabetes mellitus (IDDM). Hybridization of Bgl II-digested human genomic DNA with a cDNA clone for the HLA-DR alpha chain (pDR alpha-1) has revealed three allelic restriction fragment lengths: 3.8 kilobase pairs (kb), 4.2 kb, and 4.5 kb. Hybridization of EcoRV-digested human genomic DNA with the same probe has revealed two allelic polymorphic restriction fragment lengths: 9.2 kb and 13.0 kb. By analysis of double digests of genomic DNA from individuals homozygous for each of the allelic variants, the polymorphic restriction sites were found to be clustered near the 3' end of the HLA-DR alpha gene. The observed correlations of DR alpha Bgl II restriction site variants with serologically determined DR specificities suggest linkage disequilibrium between the DR alpha and DR beta loci. The 3.8-kb fragment is correlated with the DR1 type (Pc = 4.4 X 10(-4)); and the 4.2-kb fragment, with a subset (B8,DR3) of the DR3 type (Pc = 5.1 X 10(-4)) and with the DR6 type. The segregation pattern of HLA-DR alpha polymorphic Bgl II restriction fragments was analyzed in six IDDM families. The observed association of IDDM with the Bgl II 4.2-kb DR alpha restriction variant is higher than with existing serological markers and supports the utility of this approach in elucidating IDDM inheritance.
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PMID:Polymorphic restriction endonuclease sites linked to the HLA-DR alpha gene: localization and use as genetic markers of insulin-dependent diabetes. 299 92

Two variants of the serologically defined HLA-DR2 specificity have been reported: DR2 long and DR2 short. Distinct HLA-DR2-associated Dw subtypes have been described at the cellular level. In the Israeli population, DR2 individuals may be grouped into three clusters: DR2/Dw2, DR2/Dw12, and DR2/Dw"AZH". A new approach for the study of the polymorphism of HLA class II genes is to investigate restriction endonuclease fragments obtained from genomic DNA with specific class II cDNA probes. Previous analysis of DQ beta restriction endonuclease fragments subdivided the DR2 haplotypes into two subsets: a DQR1-positive subset and a DQR2.6-positive subset. These two subsets behave in the population as alleles that split HLA DQw1. In the present study, we have analyzed class II DQ alpha, DQ beta, and DR beta restriction fragment length polymorphism (RFLP) in HLA-DR2/Dw-typed healthy, unrelated Israeli individuals, as well as in 11 French HLA-DR2 insulin-dependent diabetes mellitus (IDDM) patients and 11 French DR-matched controls. Three DQ beta allelic clusters (DQR2.6, DQR1, and DQR12) were observed among the DR2 haplotypes and clearly correlated with Dw2, Dw"AZH", and Dw12, respectively. The vast majority of the DR2 IDDM patients (9 out of 11) fit into the DQR1 cluster which correlates with Dw"AZH", while only two patients (2 out of 11) belong to the DQR2.6 cluster (Dw2-like). In contrast, among 11 DR-matched healthy controls, 9 belonged to the DQR2.6 cluster and only 2 belonged to the DQR1 cluster. These studies establish the correlation between the DR2-associated Dw subtypes with specific RFLPs, and indicate that the frequency of the DQR1 subset which correlates with Dw"AZH" is increased in DR2 IDDM patients.
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PMID:HLA-DR2-associated Dw subtypes correlate with RFLP clusters: most DR2 IDDM patients belong to one of these clusters. 300 44

The linked polymorphic loci 5' to the insulin gene and 3' to the c-Harvey-ras-1 (c-Ha-ras) gene, both localised to the short arm of chromosome 11, have been studied in 14 type I diabetic pedigrees. The use of a cloned gene probe corresponding to the polymorphic locus adjacent to the insulin gene, in combination with the restriction endonuclease PvuII, has permitted an improvement in the resolution of sizes of insert at this locus. An MspI restriction fragment length polymorphism at the c-Ha-ras proto-oncogene locus (4 cM upstream from the insulin gene) was used to identify parental insulin gene related alleles unambiguously, and subsequently a pedigree analysis was performed to determine whether subclasses of inserts at this locus track with insulin dependent diabetes. Segregation analysis demonstrated no linkage between the polymorphic loci 5' to the insulin gene, nor 3' to the c-Ha-ras, and type I diabetes. However, a similar analysis confirmed an association between the HLA locus chromosome 6 and insulin dependent diabetes.
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PMID:DNA polymorphic haplotypes on the short arm of chromosome 11 and the inheritance of type I diabetes mellitus. 301 47


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