Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five hundred and ninety-nine patients with insulin-dependent (Type 1) diabetes mellitus were typed for Bf (factor B) polymorphism, and 318 of them for HLA-A, B and C antigens. Bf and HLA antigen frequencies were compared with those in 536 normal controls. A significant positive association between Type 1 diabetes and the rare factor B variant BfF1 was found (p less than 10(-3)), but this was present only in patients aged under 16 years at onset of the disease (p less than 0.005). There was a strongly positive linkage disequilibrium between BfF1 and HLA-B18 in the diabetic patients. This, too was especially pronounced in the juvenile onset cases, in whom it was significantly stronger than in controls (p less than 10(-3)). The known positive associations between Type 1 diabetes and HLA-B8, -B15 and -Cw3 were confirmed.
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PMID:Age-related association of insulin-dependent diabetes mellitus with BfF1 and the HLA-B18, BfF1 haplotype. 702 28

Fifty-four North Indian patients with Type I (Insulin-Dependent) diabetes mellitus who were aged 30 yr or under at onset were HLA-typed. The frequencies of HLA-BW21, BW35, and A28 were significantly increased and that of HLA-B7 was significantly reduced. On correction for the number of antigens tested, only the difference observed with HLA-BW21 for positive association and B7 for negative association remained statistically significant. HLA-B8, B15 and B18 did not demonstrate any significant association with IDDM in this series of patients. The results of the study further emphasize the well recognized race specificity in HLA antigen distribution in normal population as well as disease states. This association of HLA-BW21 with IDDM is the first report from North India.
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PMID:HLA antigens in type I (insulin-dependent) diabetes mellitus in North India. 702 26

In a previous study we determined the glucose disappearance rate (kt) in 129 newborn large-for-dates infants (LFD) born to mothers without known diabetes. Twenty-six infants (i.e. 20.6%) had elevated kt values similar to those in offspring of diabetic mothers. A follow-up study of 123 of these mothers was performed 7 years after delivery and included determination of early insulin and C-peptide response to intravenous glucose, plasma concentrations of 3-hydroxybutyrate, cholesterol, triglycerides, lipoproteins and HLA-typing. Two subjects had developed diabetes and altogether 14% had a kt below 1.0. Measures of the early insulin and C-peptide response to glucose were equally well correlated to maternal kt values (r = 0.40, P less than 0.001). Measures of the early insulin and C-peptide responses were significantly correlated (r = 0.64, P less than 0.001). The frequency distribution of HLA antigens were not different from normal and there was no association between HLA-B8 or B15 and impaired insulin response or glucose tolerance. Multiple regression and discriminate analysis of clinical and biochemical variables could not accurately identify women with high or low kt values. Multiple regression analysis using infant kt value as the dependent variable disclosed only a weak, but significant, inverse association to maternal insulin response to glucose at follow-up.
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PMID:Follow-up of women with large-for-dates infants. Early insulin and C-peptide response to intravenous glucose, blood lipids and HLA-types. 702 16

One hundred and sixty-six unrelated children and adolescents having growth-onset, insulin-dependent diabetes mellitus (IDD) were studied for pancreatic-cytoplasmic islet cell antibodies (ICA) at various times from the diagnosis of the disease. A strong association between HLA antigens A9 and Bw16 and an absence of ICA early in the course of disease was seen. On the other hand B8/Dw3 or B15/Dw4 antigens were not significantly associated with the occurrence of ICA although both these antigens are greatly increased among pediatric IDD patients in northern Finland. The finding of the association of the HLA antigens A9 and Bw16 with ICA-negativity contributes to the evidence for the heterogeneity in the genetic susceptibility to IDD.
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PMID:An islet cell antibody negative form of insulin-dependent diabetes mellitus (IDD) associated with HLA antigens A9 and Bw16. 704 30

HLA types in 121 diabetic children in Newcastle are examined in relation to their growth records. The children's height at the onset of diabetes was normal, but fell away during the course of the disease; there was low mean height velocity and failure of bone development to keep pace with chronological age. The total series shows the expected excess of HLA antigens B8, B15 and Cw3 and deficit of B7. Children with B8 are of smaller stature adjusted for bone age than those without the antigen, while children with B7 appear to do better. The results suggest that within the diabetic spectrum of genotypes the HLA antigens are relevant to growth and development.
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PMID:HLA antigens and growth in diabetic children. 712 84

The relative risk of B8/B15 heterozygotes for juvenile-onset diabetes is higher than the risk for people having B8 or B15 alone. This has been cited as evidence for genetic heterogeneity in juvenile diabetes. However, the observed relative risks are compatible with a single susceptibility allele. If disease susceptibility is recessive, for example, then an individual with two disease associated antigens is more likely to be susceptible than an individual with only one associated antigen. The relative risk for an HLA heterozygote should be intermediate between that of the respective homozygotes, so that an interaction effect of two alleles can only be supported if the heterozygote risk is significantly greater than both homozygote risks. The estimated relative risks for B8 and B15 homozygotes, based on data from four different populations, is approximately equal to the risk for B8/B15 heterozygotes. Moreover, disease manifestations which are differentially associated with B8 and B15, such as antibody production to exogenous insulin, may be due to linkage disequilibrium between HLA and other loci which are not directly related to susceptibility of juvenile diabetes. Therefore, while the susceptibility to juvenile diabetes may have several genetic forms, there is no support for distinct B8-associated and B15-associated forms of susceptibility.
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PMID:HLA antigens and susceptibility to juvenile diabetes: do additive relative risks imply genetic heterogeneity? 723 14

Diabetic nephropathy with renal failure is a major cause of death among juvenile diabetics. It is as yet unknown why some diabetics suffer from this serious renal complication while others do not, in spite of long duration of diabetes. For therapeutic reasons it is of the utmost importance to find out which patients are at risk long before the manifestation of renal insufficiency. Juvenile diabetics are know to have an increased frequency of some HLA antigens. The relationships between the HLA-A, HLA-B and HLA-C antigens and diabetic end-stage nephropathy were therefore evaluated in the present study. The study comprised 121 insulin-dependent diabetics with renal failure (mean age at onset of diabetes 13.4 leads to 7.6 (SD) years, mean pre-uraemic duration of diabetes 21.7 leads to 4.7 years), and 36 insulin-dependent diabetics (mean age at onset of diabetes 16.5 leads to 8.4 years) without renal failure despite long mean duration of diabetes (32.5 leads to 5.1 years). We found the expected significant increase in B8 and B15 and a decrease in B7 frequencies in the diabetics compared with the non-diabetic population, but no difference was found between uraemic and non-uraemic diabetics. Neither the early onset of diabetes nor the rapid appearance of renal failure was associated with any HLA frequency. The data therefore do not provide evidence of the involvement of B8 or B15 allele-associated mechanisms in the disease process leading to diabetic nephropathy with renal failure. There was a significant difference (p corrected less than 0.01) between the frequency of Bw22 in uraemic diabetics (14%) and that in non-diabetics (5%) while the frequency was near normal in non-uraemic diabetics. Further data are needed to confirm the possible association of Bw22 with diabetic nephropathy.
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PMID:HLA-antigen distribution in juvenile diabetics with end-stage nephropathy. 723 15

The frequency distributions of HLA antigens in 25 juvenile-onset diabetics (JOD) and 56 maturity-onset diabetics (MOD) belonging to a southern African black tribe (Xhosa) were compared with those of 153 non-diabetic Xhosa blacks. Unlike the findings in white JODs, there was no increase of B8 or B15 nor a reduced frequency of B7 but an apparently, significantly increased frequency of Bw35 and A2 in both Xhosa JODs and Xhosa MODs respectively. This is the first ethnic group in which an HLA antigen marker has been found for MOD. Furthermore, these findings suggest that diabetes, both JOD and MOD, in white people is a different genetic disease from the diabetes among the Xhosa tribe.
Diabetes 1980 Jan
PMID:The histocompatibility (HLA) antigen distribution in diabetes in southern African Blacks (Xhosa). 738 Jan 8

The paper presents data on the cellular and humoral immunity in different periods of insulin-dependent diabetes mellitus (with the disease standing of 0.5 +/- 0.4 years, group A; 3 +/- 1.8 years, group B; and 15 +/- 4 years, group C). Group A patients presented with the immunity system activation: increased counts of T cells, B lymphocytes, T helpers and T inductors, increased share of active T cells (that is, DR positive ones), elevated content of IgM, IgG, IgA (214 +/- 51 mg%, 1200 +/- 124 mg%, 250 +/- 34 mg%, respectively) as against the reference group (156 +/- 74, 914 +/- 387, 189 +/- 49 mg%, respectively) (p < 0.01). In group B patients, who suffered a longer disease, the immunity parameters were within the normal range, and in group C patients, in whom the disease standing was the longest, these shifts were contrary-wise as against those in group A, that is, T and B cell counts were lowered, as were the counts of T-helpers-inductors, Ig levels, and the phagocytosis index was 65 +/- 5 vs. 85 +/- 10% in the controls (p < 0.05), the phagocytosis level being 4 +/- 2 vs. 10 +/- 2 in the controls (p < 0.05). The authors analyze the association of the HLA system characteristics with the immunity shifts. Patients with the HLA A9, B8, B15, B18, DR3, DR4 presented with significant shifts in the immunity status as against those with the HLA A1, A10, B5, B12, B16, B27, DR5, DR7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunologic characterization of patients with insulin-dependent diabetes mellitus with varying duration of disease]. 805 69

We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-alpha and TNF-beta by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. Significant differences in TNF-alpha secretory capacity between TNF NcoI restriction fragment length polymorphisms, TNFa and TNFc microsatellite alleles and DR alleles were identified. No correlation with TNF-beta secretory capacity was found for any of the markers studied. TNF genotyping allowed us to define four extended HLA haplotypes which correlate with TNF-alpha secretory capacity. Two of these are DR4 positive: DQw8, DR4, TNFB*1, TNFa6, B44, A2 and DQw8, DR4, TNFB*2, TNFa2, B15, A2. Individuals carrying the TNFB*2, TNFa2 haplotype had a higher TNF-alpha secretory capacity than those carrying the TNFB*1, TNFa6 haplotype. In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas the TNFa6 allele was more frequent in control individuals. In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-alpha response. These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM.
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PMID:Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. 809 42


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