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  • 1
    Electronic Resource
    Electronic Resource
    Evidence that the reduced number of natural killer cells in Type 1 (insulin-dependent) diabetes may be genetically determined (1987)
    Springer
    Diabetologia 30 (1987), S. 907-911 
    Details
    ISSN: 1432-0428
    Keywords: Natural killer cells ; identical twins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Viruses may cause Type 1 (insulin-dependent) diabetes. We wondered whether the number and function of natural killer cells, which are important in anti-viral defense, are disturbed in diabetic patients. We studied 16 recently diagnosed Type 1 diabetic patients, 18 Type 1 diabetic patients diagnosed more than 15 years previously, 18 Type 2 (non-insulin-dependent) diabetic patients and 23 control subjects. We determined the number of natural killer cells (expressed as log10%) using anti-Leu 11 monoclonal antibody and the function (in log10 lytic units) concurrently using a 51Cr release assay with K 562 as target cells. We found that the number of natural killer cells was reduced in Type 1 diabetes (1.01±0.04) as compared with Type 2 diabetic patients (1.16±0.04, p=0.004) and normal control subjects (1.16±0.04, p=0.006). To establish whether the reduced natural killer cell number is genetically determined we studied 19 identical twin pairs discordant for Type 1 diabetes; we found that even the non-diabetic co-twins had a reduced natural killer cell number (0.93±0.05, p= 0.0006) as compared with normal control subjects. Natural killer cell function was similar in all groups while natural killer activity per cell was significantly increased in the recently diagnosed diabetic patients (1.63±0.07) as compared with long-standing diabetic patients (1.26±0.26, p= 0.03) and controls subjects (1.36±0.07, p= 0.006). In conclusion the reduced number of natural killer cells in Type 1 diabetes appears to be genetically determined while their activity at diagnosis is increased.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00295872
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Islet-cell antibodies as predictors of the later development of Type 1 (insulin-dependent) diabetes (1989)
    Springer
    Diabetologia 32 (1989), S. 382-386 
    Details
    ISSN: 1432-0428
    Keywords: Idenitical twins ; islet-cell antibodies ; Type 1 ; (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine the value of islet-cell antibodies, both complement-fixing and non-complement-fixing, in predicting the later development of Type 1 (insulin-dependent) diabetes, we studied different groups of identical twins. Twelve twins have developed diabetes and 11 of these had non-complement-Fixing islet-cell antibodies before diagnosis, and eight out of nine tested had complement-fixing islet-cell antibodies. Of the twins who have remained non-diabetic for many years and are now unlikely to develop diabetes, twelve have had non-complement-fixing islet-cell antibodies at some stage but only four have ever had complement-fixing antibodies. In 29 non-diabetic co-twins tested within 5 years of the diagnosis of diabetes in the affected twin the presence of islet-cell antibodies, especially complement-fixing, predicted the progression to frank diabetes with a high specificity (100%), sensitivity (88%) and predictive value (100%). In pairs remaining discordant the antibodies were found more frequently in the diabetic than the non-diabetic twin. We conclude that the presence of islet-cell antibodies is not genetically determined and can occur without progression to diabetes. However, the presence of islet-cell antibodies, especially complement-fixing, in non-diabetic twins tested soon after the diagnosis of their co-twin, indicates a high risk for the development of diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00277263
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  • 3
    Electronic Resource
    Electronic Resource
    A new marker in the HLA class I region is associated with the age at onset of IDDM (1995)
    Springer
    Diabetologia 38 (1995), S. 623-628 
    Details
    ISSN: 1432-0428
    Keywords: Key words IDDM ; major histocompatibility complex ; immunogenetics ; autoimmunity ; HLA and disease.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The (MHC) class II association with insulin-dependent diabetes mellitus (IDDM) is well documented. However, it is likely that genes within the MHC class III and the class I region also play a role in determining susceptibility to IDDM. In this study we have used a novel molecular probe to investigate the class I P3A and P3B loci of 179 patients with IDDM and 142 normal control subjects. A highly significant increase in the frequency of the class I P3 4.0;1.5 kilobase (kb) and 4.0;1.8;1.5 kb genotypes was found in patients compared to the control subjects (χ 2 46.8, 6 df, p 〈 0.0001). The association with the P3B 1.5 kb allele was strongly associated with the age at onset of diabetes, being present in 96.2 % of subjects who developed diabetes between the age of 10–20 years compared to 55.0 and 74.6 % who developed diabetes before 10 years or after 20 years, respectively (χ 2 31.4, p 〈 0.0001). There was no evidence for linkage disequilibrium between the DQA1 and DQB1 loci and P3B suggesting that this is an independent association. In conclusion, these results suggest that genes in both the MHC class I and II regions confer susceptibility to IDDM and are related to the age at onset of the disease. [Diabetologia (1995) 38: 623–628]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050329
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Increased proinsulin levels as an early indicator of B-cell dysfunction in non-diabetic twins of Type 1 (insulin-dependent) diabetic patients (1988)
    Springer
    Diabetologia 31 (1988), S. 182-184 
    Details
    ISSN: 1432-0428
    Keywords: Proinsulin ; insulin ; C-peptide ; identical twins ; Type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose tolerance and insulin secretion were studied in two groups of non-diabetic identical twins of recently-diagnosed Type 1 (insulin-dependent) diabetic patients: (1) a group of 5 twins with islet cell antibodies, and (2) a group of 6 twins without. Despite similar fasting glucose, insulin and C-peptide concentrations both groups of twins had significantly higher fasting proinsulin concentrations than the control group (p〈0.05). The twins with complement-fixing islet cell antibodies had reduced glucose tolerance and clearance, whilst the twins without islet cell antibodies did not. Neither group of twins showed any abnormality in insulin, C-peptide or proinsulin response to oral or intravenous glucose. We conclude that increased fasting proinsulin levels precede abnormalities of insulin secretion, and are an early indication of minor B-cell damage in these twins irrespective of their risk of developing diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00276853
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    The significance of the concordance rate for Type 1 (insulin-dependent) diabetes in identical twins (1988)
    Springer
    Diabetologia 31 (1988), S. 747-750 
    Details
    ISSN: 1432-0428
    Keywords: Concordance ; identical twins ; Type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied prospectively 49 non-diabetic identical twins of recently-diagnosed Type 1 (insulin-dependent) diabetic patients for up to 24 years (median 9 years). During this time 15 developed Type 1 diabetes. Actuarial analysis indicates that by 12 years 34% of the twins will have developed Type 1 diabetes and that thereafter only another 2% will do so. Inevitable bias in ascertainment of the twins makes it likely that the true figure is less. We conclude that factors which are not genetically determined must be important in the pathogenesis of the disease. The rates of developing Type 1 diabetes in the co-twins declines sharply in the years after diagnosis of the index twin, which suggests that the initiation of the process leading to Type 1 diabetes occurs within a finite, and not a prolonged, period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00274777
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  • 6
    Electronic Resource
    Electronic Resource
    Complement in Type 1 (insulin-dependent) diabetes (1987)
    Springer
    Diabetologia 30 (1987), S. 823-823 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275751
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    Paper (German National Licenses)
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  • 7
    Electronic Resource
    Electronic Resource
    A new marker in the HLA class I region is associated with the age at onset of IDDM (1995)
    Springer
    Diabetologia 38 (1995), S. 623-628 
    Details
    ISSN: 1432-0428
    Keywords: IDDM ; major histocompatibility complex ; immunogenetics ; autoimmunity ; HLA and disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The (MHC) class II association with insulin-dependent diabetes mellitus (IDDM) is well documented. However, it is likely that genes within the MHC class III and the class I region also play a role in determining susceptibility to IDDM. In this study we have used a novel molecular probe to investigate the class I P3A and P3B loci of 179 patients with IDDM and 142 normal control subjects. A highly significant increase in the frequency of the class I P3 4.0;1.5 kilobase (kb) and 4.0;1.8;1.5 kb genotypes was found in patients compared to the control subjects (x 2 46.8, 6 df, p〈0.0001). The association with the P3B 1.5 kb allele was strongly associated with the age at onset of diabetes, being present in 96.2% of subjects who developed diabetes between the age of 10–20 years compared to 55.0 and 74.6% who developed diabetes before 10 years or after 20 years, respectively (x 2 31.4, p〈0.0001). There was no evidence for linkage disequilibrium between the DQA1 and DQB1 loci and P3B suggesting that this is an independent association. In conclusion, these results suggest that genes in both the MHC class I and II regions confer susceptibility to IDDM and are related to the age at onset of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400734
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    Paper (German National Licenses)
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