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)

Common variable immunodeficiency is a disorder characterised by hypogammaglobulinemia with B-lymphocytes in peripheral blood and repeated infections. We report a child with a diagnosis of diabetes mellitus and celiac disease during lactation, and in whom common variable immunodeficiency was diagnosed at the age of 5. During evolution of the disease he presented multiple respiratory infections in spite of substitution therapy with gamma globulins. He presented pulmonary fibrosis with a pulmonary volume reduced, and a spirometric restrictive patron. Immunologically, he presents reduction in CD4 lymphoid population. He expresses the alleles DQ2 A1 0501 and B1 which are strongly associated with susceptibility to insulin-dependent diabetes mellitus and celiac disease, but don't express antigens HLA class II DR3 and DR4 that are more frequent in these entities. The main disease and all the complications had affected his curve pondostatural.
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PMID:Common variable immunodeficiency, insulin-dependent diabetes mellitus and celiac disease. 1126

It has been postulated that variation in the distribution of human leukocyte antigen (HLA)-encoded susceptibility alleles for insulin-dependent diabetes mellitus (IDDM) is the genetic basis for variation in the incidence of the disease between populations. The aim of this study was to characterize HLA-encoded susceptibility to IDDM in Hungary and to identify whether HLA-DRB1/DQ-encoded susceptibility could account for the five times lower incidence of disease in Hungary compared with Finland. The haplotypes DRB1*03-DQA1*05-DQB1*02 (DRB1*03-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DRB1*04-DQ8) were significantly associated with disease in both populations. Three genotypes incorporating either or both of these haplotypes accounted for over 70% of the diabetic population in both races. The combined background frequency and the degree of risk as measured by odds ratios of these HLA-DRB1-DQ genotypes were not significantly different in the two countries. Comparison of the DRB1*0401-DQ8 haplotype between the two races suggested a role for HLA-B alleles in susceptibility. These data indicate that the susceptibility associated with high risk DRB1-DQ genotypes alone is insufficient to account for the fivefold variation in incidence of IDDM between Hungary and Finland. Other genetic and/or environmental influences must be involved.
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PMID:HLA alleles and IDDM in children in Hungary: a comparison with Finland. 1129 72

The class II major histocompatibility complex (MHC) glycoproteins HLA-DQ8 and HLA-DQ2 in humans and I-A(g7) in nonobese diabetic (NOD) mice are the major risk factors for increased susceptibility to type 1 diabetes. Using X-ray crystallography, we have determined the three-dimensional structure of DQ8 complexed with an immunodominant peptide from insulin. The similarity of the DQ8, DQ2 and I-A(g7) peptide-binding pockets suggests that diabetes is caused by the same antigen-presentation event(s) in humans and NOD mice. Correlating type 1 diabetes epidemiology and MHC sequences with the DQ8 structure suggests that other structural features of the P9 pocket in addition to position 57 contribute to susceptibility to type 1 diabetes.
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PMID:Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes. 1137 36

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (P(alb)) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg. kg(-1). day(-1). Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of P(alb) in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced P(alb) significantly in concentration ranges from 10(-6) to 10(-14) mol/l compared with results in control glomeruli. The effect on P(alb) may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the P(alb) defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.
Diabetes 2001 Nov
PMID:Modulation of incipient glomerular lesions in experimental diabetic nephropathy by hypotensive and subhypotensive dosages of an ACE inhibitor. 1167 43

An association has recently been described between increased birth weight and increased risk of childhood-onset type 1 diabetes. Whether this relationship is explained by genes associated with both increased birth weight and increased risk of type 1 diabetes is unknown. In the present study, we tested the association between birth weight and HLA-DQ genotypes known to confer risk for type 1 diabetes among 969 nondiabetic children randomly selected from the Norwegian population. We found that HLA genotypes previously shown to confer risk for type 1 diabetes were associated with reduced birth weight (the mean difference in birth weight between the DQB1*0602/DQB1*0602 and DQ8/DQ2 genotypes was 354 g [95% CI 105-604]), which was opposite of that expected if HLA genes explained the birth weight-type 1 diabetes association.
Diabetes 2001 Dec
PMID:Diabetes-associated HLA-DQ genes and birth weight. 1172 75

There are large variations in the incidence of Type I (insulin-dependent) diabetes mellitus within Europe, ranging from 3.2 cases per 100,000 person-years in the Republic of Macedonia to more than 40 new cases per 100,000 person-years in Finland. This variation could be caused by differences in the distribution of genetic susceptibility markers, by differences in the distribution of environmental disease determinants or by a combination of both. To assess how much genes contribute to this variation, we correlated the level of incidence of Type I diabetes with the prevalence in the general population of genetic susceptibility and protective markers encoded by the human leukocyte antigen (HLA)-DQ loci. Positive association was found for the combined group of genotypes associated with Type I diabetes risk (p < 0.001). The whole positive effect was, however, accounted for by the HLA-DQ2/ DQ8 (DQA1*0501-DQB1*0201/DQA1*0301-DQB1*0302) and HLA-DQ4/DQ8 (DQA1*0401-DQB1*0402/DQA*0301-DQB1*0302) genotypes (p < 0.001 and p < 0.004, respectively). No correlation was found between incidence of Type I diabetes and population prevalence of genotypes not encoding for aspartate on position 57 on the HLA-DQbeta chain. It was not possible to detect any negative correlation between Type I diabetes incidence and the prevalence of HLA-genotypes conferring protection against Type I diabetes in a population (HLA-DQA1*0102-DQB1*0602/X). The results suggest that a substantial part of the transnational variation in the incidence of childhood-onset Type I diabetes in Europe is explained by variations between populations in the distribution of particular DQ genotypes which confer a high risk of Type I diabetes in the general population.
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PMID:Correlations between the incidence of childhood-onset type I diabetes in Europe and HLA genotypes. 1172 18

The contribution of MHC class II haplotypes to susceptibility to type I diabetes has been clearly established, and interest has now focused on the effects of additional genes in the MHC region. We have investigated the central MHC alleles on 8.1 ancestral haplotype (HLA-A1, B8, DR3, DQ2), as it is well conserved in Caucasian populations. The HLA-DR3-DQ2 genotype is a recognized risk factor for type I diabetes. Single nucleotide polymorphisms and microsatellites in the MHC were used to map segments of the 8.1 ancestral haplotype carried by type I diabetic and control subjects expressing either HLA-B8 or DR3, but not both these markers. In this way we controlled for the diabetogenic effect of carriage of DR3. Alleles of the 8.1 ancestral haplotype between TNFA-308/D6STNFa and HLA-B were carried with significantly greater frequency in B8(-), DR3(+) type I diabetic patients compared with B8(-), DR3(+) controls. This interval was marked by a BAT1 gene polymorphism and a MIB microsatellite allele.
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PMID:Localization of central MHC genes influencing type I diabetes. 1175 5

According to the most recent classification of diabetes mellitus the latent autoimmune diabetes in adults belongs to the group of type 1 autoimmune diabetes mellitus, as a slowly progressive form. It is not clear whether LADA is a distinct clinical entity or it is a part of the clinical spectrum of type 1 diabetes mellitus. The authors compare the antropologic (body mass index, waist to hip ratio), immunologic (occurrence of islet cell cytoplasmic autoantibodies and autoantibodies against glutamic acid decarboxylase and tyrosin phosphatase), genetic (HLA DR and DQ alleles known to be associated to type 1 diabetes mellitus) characteristics and occurrence of the features of the metabolic syndrome in the groups of type 1 and type 2 diabetes and LADA. 81 type 1 and 190 type 2 diabetics and 38 LADA patients were involved into the study. Freshly diagnosed type 1 diabetics served for controls of the autoantibody study: 48 patients manifested < or = 16 years of age and 89 type 1 diabetics manifested above 16 years of age. The three main diabetic groups differed in age: the average age in the type 1, type 2 and LADA groups were 37, 63 and 58 years respectively. There was no difference among the three groups in gender. The duration of the disease differed significantly between the type 2 and LADA groups (4.0 and 8.0 years respectively). In spite of the shorter duration of the disease in the LADA group, compared to the type 2 diabetics the frequency of insulin dependency was significantly higher in the LADA (81.6%) than in the type 2 group (46.7%). The BMI and WHR were comparable between the type 1 and LADA patients (average values were 23 and 0.83 in type 1 patients and 23.25 and 0.89 in LADA). The type 2 group differed significantly from type 1 and LADA (average values were 29.1 and 0.5). The concentration of glycated hemoglobin was comparable in the three groups. But there was a significant difference in HbA1c concentration between the freshly diagnosed subgroups of type 1 and LADA patients: 10.85% and 8% respectively. The fasting C-peptid levels were significantly higher in the sera of type 2 diabetics (0.75 pmol/l) compared to type 1 (0.2 pmol/l) and LADA patients (0.29 pmol/l). There was a significant difference in C-peptid concentrations between the type 1 and LADA groups, too. The insulin deficiency in LADA seemed to be not as severe as in type 1 diabetes. The serum total cholesterol and triglyceride levels were significantly higher and the HDL cholesterol concentration significantly lower in type 2 diabetics comparing to type 1 and LADA patients and there was no significant difference in this respect between the type 1 and LADA groups. The frequency of occurrence of hypertension differed no significantly between type 2 and LADA, but that of in type 1 diabetes was significantly lower than both type 2 and LADA. The occurrence of multiple autoantibodies (ICA + GADA + anti-IA2) was much more frequent in type 1 diabetes compared to LADA. In the sera of LADA patients the occurrence of ICA and GADA alone or ICA + GADA was characteristic (31.5% - 21.1% - 15.8% respectively). There was no difference between type 1 diabetes and LADA in the occurrence of the alleles of the MHC kown to be associated with type 1 diabetes. The occurrence of the haplotypes HLA DQ2/DR3 and/or DQ8/DR4 was observed in two thirds of type 1 diabetic and LADA patients. Chronic diabetic complications were observed in all of the groups and there was only a secondary connection of the complications with the type of the diabetes. Based on the results the authors suggest that LADA is a part of the clinical spectrum of type 1 diabetes of autoimmune origin.
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PMID:[Latent autoimmune diabetes in adults(LADA): part of the clinical spectrum of type-1 diabetes mellitus of autoimmune origin]. 1177 Jan 76

Genetic susceptibility to type 1 diabetes is determined by a combination of HLA-DQ and DRB1 alleles. In the present study, HLA associations with type 1 diabetes were investigated in the Jamaican population. DRB1 and DQ genotyping was performed on 45 type 1 diabetic patients and 132 control subjects born and resident in Jamaica. The small number of patients available for study reflected the low prevalence of type 1 diabetes in Jamaica. The results were compared with those from other African heritage populations and white Caucasians. The highest relative risk was associated with the DRB1*03-DQ2/DRB1*04-DQ8 genotype. Both DRB1*0401-DQ8 and DRB1*0408-DQ8 were positively associated with disease. DRB1*0408-DQ8 is uncommon amongst white Caucasians, where DRB1*0401-DQ8 is the major predisposing haplotype. The DRB1*1503-DQ6 haplotype was associated with protection from diabetes in the Jamaican population. This haplotype is rare amongst white Caucasians, where DRB1*1501-DQ6 is the protective haplotype. Data from African heritage populations suggest that DRB1*1503-DQ6 might be less protective than DRB1*1501-DQ6. DRB1*03-DQA1*0401-DQB1*0402 was associated with protection from diabetes in the Jamaican population, whereas in white Caucasians DRB1*08-DQA1*0401-DQB1*0402 is predisposing. These data demonstrate that comparison of genetic associations with type 1 diabetes in races with population-specific DRB1-DQ haplotypes provides new information as to the exact determinants of disease susceptibility. Further support is provided for roles of the DQ genes and the DRB1 gene (or a gene in linkage disequilibrium with it) in determining susceptibility to type 1 diabetes.
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PMID:HLA-DQ and DRB1 polymorphism and susceptibility to type 1 diabetes in Jamaica. 1184 88

Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.
Diabetes 2002 May
PMID:Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes. 1197 29


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