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- Christie, M., et al.
(author)
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Antibodies to a Mr-64000 islet cell protein in Swedish children with newly diagnosed Type 1 (insulin-dependent) diabetes
- 1988
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In: Diabetologia. - 0012-186X. ; 31:8, s. 597-602
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Journal article (peer-reviewed)abstract
- Sera from 40 Swedish children diagnosed as having Type 1 (insulin-dependent) diabetes mellitus during a one year period along with 40 age and geographically matched control subjects were tested for antibodies to a Mr-64000 islet protein by immunoprecipitation of 35S-methionine-labelled rat islet amphiphilic proteins. Of the 40 diabetic patients, 29 (73%) were found to be positive whereas all 40 control subjects were negative. Samples were also tested for titres of islet cell cytoplasmic antibodies by indirect immunofluorescence on frozen sections of human pancreas. In the diabetic group, 30 of the 40 patients (75%) were positive for islet cell cytoplasmic antibodies compared with 2 of the 40 control subjects (5%). A comparison of levels of antibodies to the Mr-64000 protein with islet cell cytoplasmic antibodies revealed a weak (rs=0.46), but significant (p<0.01) correlation between the two tests. There was no effect of age or sex on levels of antibodies to the Mr-64000 protein. These results in population-based diabetic children and control subjects demonstrate a high frequency of antibodies to the Mr-64000 protein at the time of clinical onset.
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2. |
- Landin-Olsson, M, et al.
(author)
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Epidemiological and genetic aspects on islet autoimmunity in childhood insulin-dependent diabetes.
- 1988
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In: Genetic susceptibility to environmental factors : a challenge for public intervention : [First International Ernhold Lundström Symposium, Malmö, Sweden, May 14-16, 1987] - [First International Ernhold Lundström Symposium, Malmö, Sweden, May 14-16, 1987]. - 9122012621 ; , s. 87-93
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Book chapter (peer-reviewed)
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3. |
- Landin-Olsson, M., et al.
(author)
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Islet cell and other organ-specific autoantibodies in all children developing Type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children
- 1989
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In: Diabetologia. - 0012-186X. ; 32:6, s. 387-395
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Journal article (peer-reviewed)abstract
- The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p<0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+- ATPase (3%) were all increased in the patients compared with the control children, being 2% (p<0.001), 2% (p<0.01), and 0.3% (p<0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.
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5. |
- Madsen, O D, et al.
(author)
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A two-colour immunofluorescence test with a monoclonal human proinsulin antibody improves the assay for islet cell antibodies
- 1986
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In: Diabetologia. - : Springer-Verlag New York. - 0012-186X .- 1432-0428. ; 29:2, s. 8-115
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Journal article (peer-reviewed)abstract
- The conventional indirect immunofluorescence assay for islet cell antibodies was compared with a two-colour immunofluorescent assay to detect both islet cell antibodies with fluorescein isothiocyanate-labeled rabbit anti-human IgG and pancreatic B cells with a monoclonal human proinsulin antibody and Texas red-labeled sheep anti-mouse IgG. Determinations of end-point titres showed a correlation between the new two-colour immunofluorescent assay and the conventional indirect immunofluorescent assay in 1) selected sera positive for islet cell antibodies and insulin autoantibodies rs = 0.93 (p less than 0.01) or for islet cell antibodies alone rs = 0.99 (p less than 0.005) and 2) sera from children or young adults with newly diagnosed Type 1 (insulin-dependent) diabetes rs = 0.95 (p less than 0.0001). No interference between the monoclonal human proinsulin antibodies and islet cell antibodies with or without insulin autoantibodies or between the two second fluorescent antibodies was detected. It is concluded that the two-colour immunofluorescence assay is advantageous since it is possible to mix the reagents to avoid a more time-consuming and technically complicated assay, the presence of B cells can be confirmed in each section to permit detection of B cell cytoplasmic antibodies and microscopic evaluation is easier and more accurate, particularly in islet cell antibody negative samples.
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6. |
- Hartling, Svend G, et al.
(author)
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Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity
- 1989
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 38:10, s. 1271-1274
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Journal article (peer-reviewed)abstract
- Based on the recent demonstration of elevated serum proinsulin levels in cystic fibrosis patients with impaired glucose tolerance, it was hypothesized that proinsulin could be an indicator of altered β-cell function. We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for >6 yr. The results from this group were compared with the results from 41 healthy age- and sex-matched control subjects with no family history of diabetes. Median (range) fasting proinsulin in siblings was 8.9 pM (1.7–58 pM) vs. 3.8 pM (<1.2–28 pM) in control subjects (P < .00001). There was no difference between the groups in fasting blood glucose concentrations. Both groups had fasting insulin concentrations within the normal range with a tendency toward lower values in the siblings: 108 pM (60–237 pM) vs. 118 pM (71–175 pM) (P = .07). The 99 siblings were subdivided into groups according to HLA sharing with their diabetic proband. The concentration of proinsulin, insulin, and blood glucose among the groups of 33 HLA-identical, 40 HLA-haploidentical, and 26 nonidentical siblings did not differ significantly. The fasting proinsulin level did not correlate with fasting levels of insulin, blood glucose, age, or body weight. We conclude that fasting proinsulin is elevated in healthy siblings of IDDM patients, whereas fasting insulin is normal or slightly decreased independent of HLA identity with their diabetic sibling. Elevated proinsulin levels could represent a family trait, perhaps mirroring a β-cell more vulnerable to destruction, or it could reflect previous β-cell damage that does not lead to IDDM.
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