Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred ninety-nine gravida with gestational diabetes mellitus (GDM) defined as "carbohydrate intolerance of varying severity with onset or first recognition during pregnancy" have been stratified into subgroups on the basis of fasting plasma glucose and evaluated for further phenotypic and genotypic heterogeneity. A significantly greater proportion of the women in all our groups were older and heavier than in a "control" population of 148 consecutive gravida with documented normal oral glucose tolerance. After correction for age and weight by covariate analysis, absolute insulinopenia in response to oral glucose could be demonstrated in all GDM groups, although exceptions were present in each. The incidence of diabetes in the mothers of our patients with GDM was 8-fold greater than in controls; the incidence in fathers did not deviate from control patterns. HLA-DR3 and DR4 antigens were more frequently present in GDM and the increase was statistically significant in blacks. At the time of diagnosis, cytoplasmic islet cell antibodies (ICA) were significantly more common in GDM associated with elevated fasting plasma glucose than in controls; the frequency of ICA was 18.4% (7/38) in women with fasting plasma glucose greater than or equal to 130 mg/dl. Our findings indicate that GDM entails genotypic as well as phenotypic diversity and may include patients with slowly-evolving Type I diabetes mellitus, as well as patients with Type II diabetes mellitus, and women with asymptomatic diabetes which antedated the pregnancy (i.e. pregestational diabetes mellitus). Appreciation of this heterogeneity should be incorporated into any evaluation of intervention strategies for women with GDM or into prognoses concerning their postpartum metabolic status.
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PMID:Gestational diabetes mellitus: a syndrome with phenotypic and genotypic heterogeneity. 352 23

The relative risks (RR) of the immunogenetic markers of insulin-dependent diabetes mellitus (IDDM) have been calculated in a population of 235 IDDM patients compared with a control population. The highest relative risk was that of subjects heterozygous DR3/DR4 (RR = 47, P less than 0.001) which was still more increased in those who carry this combination associated with the RFLP cluster DQR4 (RR = 72). Further, a sample of 51 secondary affected siblings of IDD index cases has been compared with 265 non affected siblings (one child of each family, excluding index cases). The highest risks have been found in addition to DR3/DR4, for DR3 alone and particularly for the combination C4BQ0, DR3 (RR = 9, p less than 0.001) suggesting a role for this peculiar association in the familial penetrance. In the group of siblings HLA-identical with the index case, only two factors showed some capacity of discriminating between affected and non affected siblings: HLA-DR3 and age (less than or equal to 10 years old at onset of IDDM in the index case) (p less than 0.01). In the group of haploidentical siblings, the combination DR3/DR4 and the associations C4BQ0, DR3 and BfF1, DR3 significantly increased the susceptibility for higher familial occurrence of the disease. If confirmed by additional family series, this scale of risk factors could be helpful in predicting risk of IDDM to siblings of diabetic children.
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PMID:[Risk factors in insulin-dependent diabetes]. 353 93

Duration of disease is the major susceptibility factor for microangiopathy. Microangiopathy does not occur without the metabolic abnormality of diabetes and there is much circumstantial evidence to implicate poor diabetic control in its pathogenesis. The rate of development and severity of complications, however, are variable even in patients with apparently similar control and about 25% of diabetics will never develop clinical evidence of microangiopathy. Studies of identical twins suggest a genetic component in the pathogenesis of retinopathy in NIDDM, and less so in IDDM, but increased capillary basement membrane thickness does not occur in the non-diabetic identical co-twins of insulin dependent diabetics. There may also be genetic heterogeneity not only of diabetes, but also of its complications, although for a given type of diabetes the prevalence of microangiopathy is often very similar in different racial groups. Associations between several different HLA molecules (particularly DR4) and microangiopathy in IDDM have been reported but not consistently confirmed. Recently the finding of an increased frequency of the B3 allotype of the fourth component of complement C4B3 in subjects with retinopathy has suggested that there is an HLA linked association. Both complement and the immunoglobulins are concerned with humoral immunity and the report of an association between a phenotype of the IgG heavy chain markers on chromosome 14 and retinopathy is of particular interest. These associations appear to be additive but independent. These reports need confirmation but provide the best evidence we have for an immunogenetic component (HLA and non-HLA linked) of the aetiology of microangiopathy, at least in IDDM. The studies of identical twins, HLA and Gm associations provide good evidence that genetic factors are involved in susceptibility to microangiopathy, at least in some diabetics, although the most relevant genes may not have been identified. Searches for better genetic markers must continue in order to identify those patients at increased risk of developing microangiopathy.
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PMID:The genetics of diabetic complications. 353 96

We previously proposed that the HLA-related genetic susceptibility to insulin dependent diabetes mellitus (IDDM) is best explained by at least two different susceptibility alleles, one preferentially associated with DR3, the other with DR4. This IDDM HLA heterogeneity model predicts that HLA haplotype sharing among affected sibpairs will be increased when the index case is a compound heterozygote (i.e., DR3/DR4). This prediction was tested and confirmed using the GAW IV IDDM data set. A significantly increased sharing of HLA haplotypes was seen when the index sib was DR3/DR4 compared to those of other genotypes (68% versus 37% sharing 2 haplotypes, p less than .01).
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PMID:HLA haplotype sharing and proband genotype in IDDM. 356 64

In order to assess interaction between HLA and Gm for susceptibility to IDDM, the families of 155 IDDM probands were typed for HLA class I, II, III antigens and 16 Gm allotypes (including G2m23). Haplotypes were obtained for both systems. Individuals bearing the equivocal haplotype Gm (formula; see text) were excluded. The frequencies of the 6 Gm haplotypes detected were comparable in IDDM patients, sibling controls and unrelated controls. The number of Gm haplotypes was compatible with random segregation whether or not the HLA genotype was taken into account. However, analysis of the HLA-DR allelic combinations showed an increase of the uncommon haplotype Gm (formula; see text) in IDDM patients bearing DR3 in the absence of DR4 (Gm (formula; see text) phenotype frequency 43% vs 24% in other allelic combinations, p less than 0.04). When 21 diabetic and 154 non diabetic siblings of the probands were compared, the combined presence of DR3/ non 4 and Gm (formula; see text) was observed in 7 (33%) affected and 11 (7%) unaffected siblings (p less than 0.001), conferring a relative risk of 6.4 to siblings who bear both markers. All DR3/non 4 positive affected siblings (7/7) also carried Gm (formula; see text) compared with 27% (11/41) of unaffected siblings (p less than 0.001). This result suggests, that in spite of the absence of segregation distortion, interaction between Gm and HLA gene products may play a role in the familial penetrance of IDDM.
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PMID:A Gm haplotype study in relation with HLA-DR in 155 insulin-dependent diabetic patients and their affected and non affected siblings. 366 50

Structural analysis of HLA class II molecular variation occurring within haplotypes implicated in specific HLA-associated diseases now provides more specific and sensitive mechanisms for investigation of genetic susceptibility to disease. Using the HLA-DR4 association with two distinct diseases, IDDM and JRA, as a model, we can conclude the following: There are at least seven distinct haplotypes which share the HLA DR4 specificity; these haplotypes include six alleles at the DR-beta genetic locus. These allelic differences are subtle, encompassing a very few clustered amino acid changes, but are sufficient to generate different patterns of T cell alloreactivity; there are at least three different alleles of DQ-beta genes associated with DR4+ haplotypes, with major structural differences recognized by biochemical analysis and by specific antibodies; different DR4-associated diseases are associated with different specific allelic variants of DR and DQ genes. DR4+ IDDM is most closely associated with the DQ 3.2 allele at DQ-beta; DR4+ JRA, on the other hand, appears to be highly associated with rare alleles at DR-beta, but not DQ. Notably, there are many alleles, and therefore DR4+ haplotypes, which are not implicated in 'HLA-DR4-associated' diseases.
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PMID:Immunogenetics of disease susceptibility: new perspectives in HLA. 377 53

The frequency distribution of alleles controlled by the factor B (Bf) and glyoxalase genes that are found close to the HLA system on chromosome 6 was studied in 170 insulin-dependent diabetic patients. The data were compared with those for HLA-A, -B and -DR antigens and were related to age of onset of diabetes. All the diabetics were ketosis prone and on permanent insulin therapy. A significant excess of BfF1 was seen in the diabetic patients (p less than 10(-4]. Glyoxalase frequency distribution showed no significant deviation from controls, whereas HLA-DR3 (p less than 10(-4] HLA-DR4 (p less than 10(-4] were increased. Breakdown of data by age of diagnosis of disease showed no increase in the frequency of BfF1 and GLO1-2 but an increase of HLA DR3 and DR4 in patients with early onset diabetes. The findings of the study are consistent with data reported by others investigators and support the notion that one or more genes mapping close to the HLA A. B and DR and to the Bf loci confer susceptibility to insulin dependent diabetes.
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PMID:Factor B (Bf) and glyoxalase genes in insulin-dependent diabetes mellitus. 385 41

Singaporean Chinese IDDM was significantly associated with AW33, BW58, DR3 and DR4. AW33, BW58 and DR3 being in strong linkage disequilibrium among the Chinese, were associated most strongly with IDDM whose onset was less than or equal to 10 years. The strength of this association showed a significant inverse relationship with age of onset. The frequency of DR4 was significantly elevated on in the 11-20 year IDDM group. The importance of DR3 in Chinese IDDM was also reflected in the observations of joint occurrences of DR antigens. In the less than or equal to 10 years subgroup, the significant association were either DR3/DRW9, DR3/DR4 or DR3/BLANK. In the 11-20 years subgroup, DR4 appeared to be more important and DR4/DR3 and DR4/BLANK were strongly associated with IDDM in this subgroup.
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PMID:HLA and insulin dependent diabetes mellitus in Singaporean Chinese. 386 60

HLA-A, B, C and DR antigen frequencies were determined in South African Negro (Black) (50) and Cape Coloured (57) patients with insulin dependent diabetes mellitus (IDDM) and in appropriate controls. The Black patients failed to show associations commonly reported for American Black patients with IDDM but did show a weakly significant increase in the DRw9 frequency. However, this antigen was rare even in the patient group and HLA associated genes do not appear to play a major role in the pathogenesis of IDDM in these people. The Cape Coloureds have a high proportion of Caucasoid genes. Coloured IDDM patients had the expected low DR2 and high DR4 frequencies. Unexpectedly the Cape Coloureds failed to show significant associations of IDDM with B8 or DR3.
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PMID:HLA-A, B, C and DR antigen associations in insulin dependent diabetes mellitus (IDDM) in South African Negro (black) and Cape coloured people. 386 79

We have studied the relative frequency of Dw specificities (defined with homozygous typing cells or primed LD (lymphocyte defined) typing reagents) associated with DR4 and DR2 in the normal and insulin-dependent diabetic population. Our findings demonstrate that there is a highly significantly increased frequency of Dw4 in DR4 positive diabetics as compared with normals and a significantly decreased frequency of Dw2 and Dw12 in the few DR2 positive insulin-dependent diabetics that we have found. In addition, we have used PLT reagents to define a new LD specificity, LD-MN2, that is associated with DR2 and is found significantly more frequently in DR2+ IDD patients than in DR2+ normals. These results suggest that determinants of import in the association between HLA-D and IDD may be more closely related to Dw than to DR.
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PMID:Insulin-dependent diabetes--associated HLA-D region encoded determinants. 387 32


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