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)

A 61-year-old woman with a 2-year history of insulin-dependent diabetes mellitus (IDDM) developed nephrotic syndrome. Renal biopsy showed minimal-change nephrotic syndrome (MCNS), and no evidence of diabetic glomerulosclerosis. Although steroid therapy was initiated, plasma urea and creatinine rose and hemodialysis was required. After 4 weeks, she responded to steroids and her renal function returned to normal. MCNS, which is not associated with diabetic glomerulosclerosis, has rarely been seen in IDDM patients with nephrotic syndrome. Her human leukocyte antigen typing was A24, BW52, BW61, DR2 and DR9. This typing has been reported to be associated with both IDDM and renal disease.
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PMID:Minimal-change nephrotic syndrome and acute renal failure in a patient with aged onset insulin-dependent diabetes mellitus and autoimmune thyroiditis. 1039 72

Gestational diabetes mellitus (GDM) is a risk factor for the development of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus postpartum. To evaluate whether there is any association of human leukocyte antigen (HLA) class II alleles (DR and DQ) with GDM and the postpartum development of IDDM, we analyzed 184 women with GDM from Germany for HLA class II alleles, islet autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A), and the postpartum development of diabetes. No elevation in the frequency of any HLA class II alleles was observed in GDM patients compared to 254 nondiabetic unrelated subjects. DR3 allele frequency was significantly increased in 43 women with islet autoantibodies [corrected P value (Pc) = 0.02], in particular in those with GADA (Pc = 0.002), or in the 24 women who developed IDDM postpartum (Pc = 0.005). In women with GADA, DR4 and DQB1*0302 were significantly elevated (Pc = 0.009). Twenty-five (59.5%) islet antibody-positive women and 17 (74%) women who developed IDDM postpartum had a DR3- or DR4-containing genotype. The cumulative risk to develop IDDM within 2 yr postpartum in GDM women with either DR3 or DR4 was 22% compared to 7% in women without those alleles (P = 0.02) and rose to 50% in the DR3- or DR4-positive women who had required insulin during pregnancy (P = 0.006). Combining the determination of susceptible HLA alleles (DR3, DR4) with islet autoantibody measurement increased the sensitivity of identifying GDM women developing postpartum IDDM to 92%, but did not improve risk assessment above that achieved using GADA measurement alone, which was the strongest predictor of IDDM. These results indicate that women with GDM who have islet autoantibodies at delivery or develop IDDM postpartum have HLA alleles typical of late-onset type 1 diabetes, and that both HLA typing and islet antibodies can predict the development of postpartum IDDM.
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PMID:Predictive value of human leukocyte antigen class II typing for the development of islet autoantibodies and insulin-dependent diabetes postpartum in women with gestational diabetes. 1040

Antigenic proliferative responses of peripheral blood mononuclear cells (PBMC) to insulin were studied in 44 type 1 new-onset diabetic subjects. Of them, 14 (32%) had a stimulation index (> or =3) above the mean + 3 SD of 39 healthy controls and of 7 of 15 (47%) diabetic patients of long duration (P = 0.001). Responses to insulin were not dictated by specific major histocompatibility complex class II association and were not observed in normal subjects with diabetes-associated human leukocyte antigen-DR/DQ alleles. Whereas no relation of PBMC reactivity with insulin autoantibodies was found, there was a positive correlation with the presence of at least one of the four autoantibodies tested and with IA-2 antibody. An interesting finding was that the proportion of patients with subsequent low insulin requirement, up to 24 months, was significantly higher in patients who showed PBMC reactivity to insulin (8 of 8) than in those who did not (10 of 24, 42%; P = 0.004). The former had a higher mean stimulation index than the latter (3.3+/-2.6 vs. 1.5+/-0.6; P = 0.006). Furthermore, interleukin-4 (IL-4) production was lower in type 1 diabetic patients who proliferated to insulin than in those who did not (23+/-15 vs. 64+/-47 pg/mL; P = 0.04), but interferon-gamma, IL-2, and IL-10 productions were similar. In conclusion, these results suggest that proliferation to insulin may reflect the presence of an higher residual beta-cell mass.
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PMID:The relationship between peripheral T cell reactivity to insulin, clinical remissions and cytokine production in type 1 (insulin-dependent) diabetes mellitus. 1040 14

Long-term prognosis in kidney transplant recipients depends on multiple factors. The purpose of this study was to quantify the influence of hyperuricemia and hyperglycemia (elements of the so-called 'syndrome X', i.e., a combination of metabolic disorders like hyperuricemia, diabetes mellitus, hyperlipidemia, and hypertension) on organ function in 350 kidney transplant recipients who had received 375 kidney transplants up to 1990 and in whom sex, age of recipient and donor, nephrologic disease, duration of dialysis, human leukocyte antigen (HLA) classification, and duration of transplant ischemia had been well matched. We found the influence of hyperuricemia on graft survival to be statistically significant (p < or = 0.05), while a statistically significant correlation between hyperglycemia and graft survival could not be detected in the present study. The transplant survival rates 2, 4, and 5 yr post-kidney-transplantation were 96.7, 80.7, and 78.7 in normogylcemic patients vs. 96.9, 85, and 82.7% in hyperglycemic ( > 100 mg,dL) kidney transplant recipients (p > 0.05). Transplant survival in hyperuricemic patients (male, > 8 mg dL; female, > 6.2 mg/dL) 2, 4, and 5 yr post-transplantation was significantly reduced (92.2, 70.6, and 68.8% vs. 98.1, 85.6, and 83.3%), as compared to normouricemic recipients. A combined presence of both hyperuricemia and hyperglycemia probably influencing the prognosis post-kidney-transplantation failed to reach the level of statistical significance. We found a significant correlation between age of recipients and plasma glucose (p < or = 0.01) and between serum uric acid concentrations and diuretic therapy (p < or = 0.05) and gender (p < or = 0.(5). In conclusion, hyperuricemia after kidney transplantation seems to reduce graft survival, whereas an influence of the carbohydrate metabolism has to be denied.
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PMID:Influence of hyperglycemia and hyperuricemia on long-term transplant survival in kidney transplant recipients. 1051 17

Previous studies have shown a high prevalence of gastric parietal cell antibodies (PCA) in type 1 diabetes, which can be accompanied by (sub)clinical autoimmune gastric disease. This study aimed to determine the grade of associated autoimmunity and to assess the pattern of prevalence of PCA by gender, age, duration of disease, age at onset of diabetes, and human leukocyte antigen (HLA) type in an adult type 1 diabetic population. Furthermore, to examine the clinical significance of being PCA positive, manifestations of gastric autoimmune disease were studied in PCA-positive and PCA-negative patients. The population studied consisted of 497 type 1 diabetics (men/women, 252/245; mean age, 40.8 +/- 12.1 yr; mean duration of disease, 16.4 +/- 10.4 yr; mean age at onset, 26.9 +/- 13.5 yr; mean hemoglobin A1c, 8.1 +/- 1.6%). Associated autoantibodies were present in 39% and PCA were present in 20.9% of the subjects, particularly in older patients. Gender, duration, and age at onset of diabetes did not influence the appearance of PCA. Antithyroid peroxidase antibodies (aTPO) were more frequent in PCA-positive patients than in those without PCA (33.6% vs. 22.4%; P = 0.025), suggesting an association between gastric and thyroid autoimmunity. We could demonstrate an association between PCA and the HLA DR5 haplotype (P = 0.001) as well, but not with HLA DR3 and/or DR4. In the PCA-positive group, iron deficiency anemia was detected in 15.4%, and pernicious anemia was found in 10.5% of subjects. These autoimmune gastric manifestations were significantly more prevalent in PCA-positive diabetics than in PCA-negative subjects, in whom the percentages were 6.9% and 0.5%, respectively (P = 0.01 and P < 0.0001). PCA were prevalent in 84.6% of patients with pernicious anemia. A gastroscopic and anatomopathological examination performed in a subgroup of 30 patients with gastric symptoms revealed atrophic gastritis in 13 of 14 PCA-positive patients and in 9 of 16 PCA-negative subjects (P = 0.04). PCA were present in 59.1% of patients with atrophic gastritis. In conclusion, a high prevalence of parietal cell antibodies and associated autoimmune gastric disease is present in PCA-positive type 1 diabetics, recommending its screening. Early detection of PCA and iron deficiency anemia, pernicious anemia, and atrophic gastritis and the subsequent care could reduce the morbidity of type 1 diabetes.
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PMID:High prevalence of manifestations of gastric autoimmunity in parietal cell antibody-positive type 1 (insulin-dependent) diabetic patients. The Belgian Diabetes Registry. 1056 50

Certain alleles of human leukocyte antigen (HLA)-DR and -DQ genes have been strongly associated with susceptibility and resistance to insulin- dependent diabetes mellitus (IDDM). To further clarify the association of HLA DQ alleles with IDDM and the influence of age at onset and gender on the association with IDDM, we investigated the association of HLA-DQA1, -DQB1 in 54 childhood onset Chinese (21 male) IDDM patients and 65 normal controls by using polymerase chain reaction-sequence specific primer (PCR-SSP). The mean age plus or minus SD at onset of IDDM patients was 8.37+/-3.54 year old. Our results revealed that the frequencies of DQA1 *0301, *0302, DQB1 *0201, and *0302 in IDDM patients were significantly higher than that in the control group (p < 0.025, < 0.005, < 0.001, and < 0.001, respectively). The frequency of DQA1 *0301, *0302, DQB1 *0201, and *0302 were susceptible alleles to IDDM with relative risks of 2.0, 3.5, 5.0 and 4.3, respectively. The protective alleles to IDDM were DQA1 *0101, *0103, DQB1 *0301, *0503, and *0602. We divided IDDM patients into three groups according to age at onset (1-5, 6-10, and 11-15 years old). The frequency of DQA1 *0302 decreased as age increased, and the frequency of DQA1 *0501 increased as age increased. Our results also showed that male IDDM patients had higher frequencies of DQA *0501, DQB1 *0201 than female IDDM patients (p < 0.025 and < 0.025, respectively), while female IDDM patients had higher frequencies of DQB1 *0502 than male IDDM patients (p < 0.05). In our study significant susceptibility haplotypes to IDDM were DQA1 *0301-DQB1 *0302, DQA1 *0501-DQB1 *0201, DQA1 *0301-DQB1 *0201, and DQA *0302-DQB1 *0201.
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PMID:The influence of age at onset and gender on the HLA-DQA1, DQB1 association in Chinese children with insulin dependent diabetes mellitus. 1060 12

The prevalence of human leukocyte antigen (HLA) DQB1 and DQA1 alleles has been determined in 78 Kuwaiti Arab children with insulin-dependent diabetes mellitus (IDDM) and in 57 normal healthy controls with similar ethnic background. The typing of HLA-DQ alleles was carried out using an allele-specific DNA-based polymerase chain reaction (PCR) SSP method. DR typing was also performed in 212 control subjects using PCR-SSP (sequence specific primer) method. A significantly higher frequency of DQB1*0201 allele was found in IDDM cases compared to the controls (p<0.001). There was no significant difference in the prevalence of DQB1 alleles *0302, *0501, and *0602 between IDDM cases and the controls. In contrast, DQB1 alleles *0301, *0402, *0502, *0602, and *0603 were represented at a somewhat higher frequency in controls compared to the IDDM cohort. The frequency of DQA1 allele *0301, which encode for an Arg at codon 52, was significantly higher in the IDDM patients compared to the controls (p<0.001). The frequency of DQA1 allele *0302 was also higher in IDDM cases than controls (p = 0.034) but the difference was less pronounced than DQA1*0301. Amongst the Arg52 alleles, no significant difference was detected in the frequency of *0401 between IDDM cases and the controls and the allele *0501 was detected only in controls. For non-Arg52 alleles *0103, *0104, and *0201, the differences in the two groups were not significant, with the exception of allele *0104 (p = 0.024). DR3 was the most common type in the Kuwaiti general population (28%) and DRB1*0301 was detected in 41% of the individuals with DR3 specificity. Analysis of HLA-DQBI/DQA1 haplotypes from IDDM cases and controls revealed a significantly high frequency of haplotype DQA1*0301/DQB1*0201 between Kuwaiti IDDM cases (49/78, 63%) and the controls (8/57, 14%).
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PMID:Prevalence of human leukocyte antigen DQA1 and DQB1 alleles in Kuwaiti Arab children with type 1 diabetes mellitus. 1066 65

To evaluate the emergence of diabetes-associated autoantibodies in young children and to assess whether such antibodies can be used as surrogate markers of type 1 diabetes in young subjects at increased genetic risk, we studied 180 initially unaffected siblings (92 boys and 88 girls) of children with newly diagnosed type 1 diabetes. All siblings were younger than 6 yr of age at the initial sampling, and they were monitored for the emergence of islet cell antibodies (ICA), insulin autoantibodies (IAA), glutamate decarboxylase antibodies (GADA), and IA-2 antibodies (IA-2A) up to the age of 6 yr and for progression to clinical type 1 diabetes up to the age of 10 yr. All 160 siblings with DNA samples available were typed for susceptible (DQB1*02 and *0302) and protective (DQB1*0301 and *0602-03) HLA DQB1 alleles. Twenty-two siblings (12.2%) tested positive for ICA in their first antibody-positive sample before the age of 6 yr, 13 (7.2%) tested positive for IAA, 15 (8.3%) tested positive for GADA, and 14 (7.8%) tested positive for IA-2A. There were 16 siblings (8.9%) who had 1 detectable autoantibody, 5 (2.8%) had 2, and 12 (6.7%) had 3 or more. In the group of 82 siblings with increased human leukocyte antigen-defined genetic susceptibility [DQB1*02/*0302, *0302/x (x = other than *02 or a protective allele), *02/y (y = other than *0302 or a protective allele)], 18 (22.0%) tested positive for ICA in their first antibody-positive sample, 10 (12.2%) tested positive for IAA, 14 (17.1%) tested positive for GADA, and 12 (14.6%) tested positive for IA-2A. One antibody was detectable in 6 siblings (7.3%), 2 were detectable in 5 (6.1%), and 3 or more were detectable in 12 (14.6%). Fifteen siblings (18.3%) presented with clinical type 1 diabetes before the age of 10 yr. All of the progressors showed increased human leukocyte antigen-defined genetic susceptibility. Thirteen of those 15 siblings, who presented with clinical type 1 diabetes before the age of 10 yr, had at least 2 antibodies detectable before the age of 6 yr (disease sensitivity, 87%; 95% confidence interval, 60-98%). Thirteen of the 17 siblings who tested positive for 2 or more autoantibodies before the age of 6 yr developed type 1 diabetes before the age of 10 yr (positive predictive value, 76%; 95% confidence interval, 50-93%). These observations suggest that disease-associated autoantibodies can well be used as surrogate markers of clinical type 1 diabetes in primary prevention trials targeting young subjects with increased genetic disease susceptibility.
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PMID:Disease-associated autoantibodies as surrogate markers of type 1 diabetes in young children at increased genetic risk. Childhood Diabetes in Finland Study Group. 1072 50

The presence of human leukocyte antigen (HLA) haplotype DQA1*0102, DQB1*0602 is associated with protection from type 1 diabetes. The Diabetes Prevention Trial-type 1 has identified 100 islet cell antibody (ICA)-positive relatives with this protective haplotype, far exceeding the number of such subjects reported in other studies worldwide. Comparisons between ICA+ relatives with and without DQB1*0602 demonstrated no differences in gender or age; however, among racial groups, African-American ICA+ relatives were more likely to carry this haplotype than others. The ICA+ DQB1*0602 individuals were less likely to have additional risk factors for diabetes [insulin autoantibody (IAA) positive or low first phase insulin release (FPIR)] than ICA+ relatives without DQB1*0602. However, 29% of the ICA+ DQB1*0602 relatives did have IAA or low FPIR. Although half of the ICA+ DQB1*0602 relatives had a high risk second haplotype, this was not associated with the additional risk factors for diabetes. Hispanic ICA+ individuals with DQB1*0602 were more likely to be IAA positive or to have low FPIR than other racial groups. In conclusion, the presence of ICA in the relatives described here suggests that whatever the mechanism that protects DQB1*0602 individuals from diabetes, it is likely to occur after the diabetes disease process has begun. In addition, there may be different effects of DQB1*0602 between ethnic groups.
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PMID:Islet cell antibody-positive relatives with human leukocyte antigen DQA1*0102, DQB1*0602: identification by the Diabetes Prevention Trial-type 1. 1072 72

We hypothesized that genetic determinants of expression of persistent antiislet autoantibodies would similarly influence the expression of transient autoantibodies. To test this hypothesis, we prospectively evaluated sera from 478 relatives (SOC: sibling-offspring cohort) of patients with type 1 diabetes as well as 793 newborns from the general population (NEC: newborn nonrelative cohort) selected for expression of specific human leukocyte antigen haplotypes. Eight relatives of 478 (1.7% of SOC) expressed a transient autoantibody, and none had the high risk genotype DR3/4(DQ2/8). In contrast, 28 relatives (5.9%) had persistent antiislet autoantibodies, and 14 (50%) were DR3/4(DQ2/8) heterozygotes. Thirteen children of 793 (1.6% of NEC) expressed a transient autoantibody, and none had the high risk genotype DR3/4(DQ2/8). Seven of the NEC (0.9%) had persistent antiislet autoantibodies, and 4 (57.1%) were DR3/4(DQ2/8) heterozygous. Expression of persistent autoantibodies was strongly related to human leukocyte antigen status and family history of type 1 diabetes. In contrast, the expression of transient antiislet autoantibodies did not differ by family history of diabetes, and none of the DR3/4(DQ2/8) relatives and DR3/4(DQ2/8) newborns expressed transient autoantibodies. Our results indicate that children can express transient antiislet autoantibodies, but such transient autoantibodies are relatively infrequent and are not correlated with known genetic risk factors for type 1 diabetes.
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PMID:Transient antiislet autoantibodies: infrequent occurrence and lack of association with "genetic" risk factors. 1090 88


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