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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 31 (1990), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Restriction fragment length polymorphism using an HLA-DQ β-chain genomic probe showed that 63 children with insulin-dependent (type 1) diabetes mellitus (IDDM) were all (100%) positive for the BamH1 fragments 12 kb and/or 4 kb compared to 98% (62/63) for HLA-DR3 and/or 4 and 75% (47/63) for HLA-B8 and/or 15. The 36 (56%) DR3-positive children were all 4-kb-positive; however, a total of 44 (70%) children were 4-kb-positive (P 〈 0.02). The 55 (87%) DR4-positive children were all 12-kb-positive, but a total of 56 (89%) were 12-kb-positive (NS), The heterozygosity at the HLA region increased from 11/63 (18%) for HLA-B8/15 to 29/63 (46%) for HLA-DR3/4 (P 〈 0,0004) and to 37/63 (59%) for the HLA-DQ 4 kb/12 kb fragments (P 〈 0.02). The test of an equal probability ofa positive result under the adjacent pair of tests indicates that the increased risk of developing IDDM in association with HLA-DQ is to a great extent due to heterozygosity at this locus. There were no differences between the 4 kb/12 kb and the DR3/4-positive IDDM children with respect to fasting or meal-stimulated C peptide, insulin requirement, or levels of insulin antibodies formed during the first 12 months of insulin therapy. Our results support the hypothesis that HLA-DQ is closely associated with an increased risk of childhood IDDM, and when typed for at this locus parameters of the clinical course were homogeneous, suggesting that factors other than HLA-DQ may determine previously observed differences between IDDM children in clinical or functional parameters.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A study of 109 Swedish patients and 85 healthy Swedish controls with Crohn's disease (CD) by HLA class II RFLP genotyping was carried out. There was no significant association for any single DR or DQ specificity or phenotypic combination of DR and/or DO specificities among our study group of Caucasian extraction.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-5233
    Keywords: Fasting C-peptide ; Autoimmunity ; Islet cell antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To clarify the utility of islet cell antibodies (ICA) to correctly classify and predict insulin treatment in newly diagnosed diabetic subjects, ICA, body mass index (BMI), glycated hemoglobin (HbA1c), and fasting plasma C-peptide values were evaluated at and 3 years after diagnosis in 233 new, consecutively diagnosed, adult diabetic patients classified as obese or nonobese (National Diabetes Data Group, NDDG criteria). Among the 233 patients, 31 were nonobese ICA-positive (mean age at diagnosis 43±3 years), 55 nonobese ICA-negative (mean age at diagnosis 58±2 years), 7 obese ICA-positive (mean age at diagnosis 57±5 years), and 139 obese ICA-negative (mean age at diagnosis 58±1 years). Fasting C-peptide decreased (P〈0.05) in nonobese ICA-positive patients who after 3 years showed lower BMI (22.6±0.6 versus 24.5±0.4;P〈0.05), lower fasting C-peptide (0.14±0.06 nmol/l versus 0.71±0.07 nmol/l;P〈0.001), and higher frequency of insulin treatment [28/31 (90%) versus 6/45 (13%);P〈0.001] than nonobese ICA-negative patients. In obese ICA-positive patients, fasting C-peptide also decreased (Δ C-peptide 0.17±0.04 nmol/l;P〈0.05) after diagnosis, and 3 years after diagnosis, obese ICA-positive patients showed lower BMI (25.7±1.2 versus 29.8±0.4;P〈0.01) and fasting C-peptide (0.08±0.04 nmol/l versus 1.06±0.05 nmol/l;P〈0.001) and higher HbA1c values (9.92%±0.68% versus 7.39%±0.21%;P〈0.01) and a higher frequency of insulin treatment [7/7 (100%) versus 5/121 (4%);P〈0.001] than obese ICA-negative patients. Therefore, ICA detected at diagnosis of diabetes in both obese and nonobese adult patients indicate β-cell dysfunction, high HbA1c levels, and progression to insulin dependency.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; Type 2 (non-insulin dependent) diabetes ; incidence ; age ; body mass index ; HbA1c
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The differential diagnosis between Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes is complicated since no specific markers are available for either disease. In this study, 244 consecutive patients were diagnosed with diabetes mellitus during two years in Malmö (230000 inhabitants), corresponding to an incidence rate of 53·100000−1·year−1. Age, body mass index, HbA1c, C-peptide, and levels of islet cell antibodies were determined at the clinical onset, and related to the classification at diagnosis and at follow-up (n=233) after a median time of 31 (range 1–49) months. After diagnosis, 42 of 244 (17%) were started on insulin while 202 of 244 (83%) were not. Islet cell antibodies were present in 25 of 42 (60%), and in 18 of 183 (10%), respectively. In the non-insulin treated group, patients with islet cell antibodies had lower body mass index (p〈0.001), higher HbA1c (p〈0.004), and lower C-peptide (p〈0.001) than patients without. At follow-up, 11 of 18 (61%) islet cell positive patients were changed to insulin treatment, as were six other patients. Insulin was discontinued in five initially insulin-treated but islet cell antibody negative patients. The sensitivity, specificity and predictive value for insulin treatment at follow-up were for islet cell antibody positivity; 72%, 96% and 84%, respectively, and for low C-peptide value; 60%, 96%, and 80%, respectively. Islet cell antibodies and low C-peptide at diagnosis of diabetes mellitus are concluded to be useful markers to predict insulin dependence.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; insulin autoantibodies ; islet cell antibodies ; glutamic acid decarboxylase antibodies ; intravenous glucose tolerance test ; prediabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary First-degree relatives of Type 1 (insulin-dependent) diabetic patients are at increased risk for developing clinical diabetes. The presence of islet cell or insulin autoantibodies further identifies relatives at greater risk, but not all immunologic-marker-positive relatives progress to disease. Beta-cell dysfunction, however, seems to be more prevalent than clinical Type 1 diabetes, since stable subclinical pancreatic Beta-cell dysfunction may occur. Antibodies against a Mr 64,000 (64K) islet Beta-cell protein, identified as glutamic acid decarboxylase, have been reported both at and several years prior to the clinical onset of Type 1 diabetes. We measured 64K antibodies in first-degree relatives with varying degrees of Beta-cell dysfunction and risk for subsequent Type 1 diabetes to determine whether 64K antibodies improve the predictive power of islet cell antibodies and/or insulin autoantibodies. In the Seattle Family Study first-degree relatives of Type 1 diabetic patients are followed prospectively using detailed Beta-cell function tests, insulin sensitivity, quantitative evaluation of islet cell antibodies and fluid phase assay insulin autoantibodies. 64K antibodies were measured using dog islets. Relatives were selected, based on Beta-cell function to represent individuals at high (n=6) and low (n=30) risk for subsequent Type 1 diabetes. The 30 low-risk individuals followed-up for 78 months, had stable Beta-cell function, and six (20%) were negative for all autoantibodies, ten (33%) were positive for insulin autoantibodies, 16 (53%) were islet cell antibody positive while six (20%) were positive for 64K antibodies. In contrast, of the six subjects with progressively declining Beta-cell function who are therefore at high risk, two of whom have already developed Type 1 diabetes, two (33%) were positive for insulin autoantibodies, four (67%) were islet cell antibody positive, while all six (100%) were positive for 64K antibodies. We conclude that antibodies to the Mr 64,000 islet protein correlate with progressive Beta-cell dysfunction more closely than either islet cell antibodies or insulin autoantibodies, but can sometimes be present in individuals whose Beta-cell function remains stable over several years.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Key words Transmission rates ; non-inherited maternal haplotypes ; non-inherited paternal haplotypes ; HLA-DR ; HLA-DQ.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The transmission of HLA-DR and DQ was compared between 46 families with at least one child affected by insulin dependent diabetes mellitis (IDDM) and 43 healthy control families. In the patient families, there was an increased transmission of DR4 (p 〈 0.025) and DQB1*0302 (p 〈 0.01) from both parents to the index patient. There was an increased transmission of DQB1*0302 (p 〈 0.03) from the mothers only. The non-inherited maternal haplotypes showed a significantly decreased frequency (p 〈 0.01) of positively associated haplotypes (DR4-DQA1* 0301-DQB1*0302, DR3-DQA1*0501-DQB1*0201) compared to all parental haplotypes in the control families. In the control families neither transmission rates nor frequencies of non-inherited haplotypes differed from those expected in the control families. In conclusion, the observed reduction of IDDM-positively associated haplotypes in patient non-inherited maternal haplotypes, but not in non-inherited paternal haplotypes, suggests that tolerance during fetal life to maternal non-inherited HLA molecules may be important to diabetes development. [Diabetologia (1994) 37: 1105–1112]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Glutamic acid decarboxylase ; receiver-operating characteristic plot ; diagnostic accuracy ; islet cell antibodies ; autoimmunity ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n=10) and control (n=50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p〈0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0–14 year-old patients (n=105), and matched, healthy control subjects (n=157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77% and the specificity 92% compared with 8% and 98%, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methioninelabelled recombinant GAD.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Key words Glutamic acid decarboxylase, receiver-operating characteristic plot, diagnostic accuracy, islet cell antibodies, autoimmunity, diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n =10) and control (n =50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p 〈0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0–14 year-old patients (n =105), and matched, healthy control subjects (n =157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77 % and the specificity 92 % compared with 8 % and 98 %, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7 % (6 of 81) and GAD65 antibodies and ICA in 89 % (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methionine-labelled recombinant GAD. [Diabetologia (1994) 37: 344–350]
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 35 (1992), S. A9 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Transmission rates ; non-inherited maternal haplotypes ; non-inherited paternal haplotypes ; HLA-DR ; HLA-DQ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The transmission of HLA-DR and DQ was compared between 46 families with at least one child affected by insulin dependent diabetes mellitis (IDDM) and 43 healthy control families. In the patient families, there was an increased transmission of DR4 (p〈0.025) and DQB1*0302 (p〈0.01) from both parents to the index patient. There was an increased transmission of DQB1*0302 (p〈0.03) from the mothers only. The non-inherited maternal haplotypes showed a significantly decreased frequency (p〈0.01) of positively associated haplotypes (DR4-DQA1* 0301-DQB1*0302, DR3-DQA1*0501-DQB1*0201) compared to all parental haplotypes in the control families. In the control families neither transmission rates nor frequencies of non-inherited haplotypes differed from those expected in the control families. In conclusion, the observed reduction of IDDM-positively associated haplotypes in patient non-inherited maternal haplotypes, but not in non-inherited paternal haplotypes, suggests that tolerance during fetal life to maternal non-inherited HLA molecules may be important to diabetes development.
    Type of Medium: Electronic Resource
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