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  • 1
    Electronic Resource
    Electronic Resource
    Alerations of lymphocyte subsets in children of diabetic mothers (1994)
    Springer
    Diabetologia 37 (1994), S. 1132-1141 
    Details
    ISSN: 1432-0428
    Keywords: Lymphocyte subsets ; insulin-dependent diabetes mellitus ; gestational diabetes ; cord blood
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the impact of diabetic mothers on the maturation of the immune system in their offspring, immunophenotypic markers of major lymphocyte subpopulations were evaluated by two-colour flow cytometric analysis in 160 healthy children of diabetic mothers (100 with insulin-dependent diabetes mellitus (IDDM); 48 with gestational diabetes), including 22 neonates, 45 infants aged 8–12 months, 46 children aged 1–2 years, 29 children aged 3–6 years and 18 children aged 7–17 years. Results were compared with 21 neonates of healthy mothers from our hospital and with 110 paediatric subjects of a reference population. In neonates of diabetic mothers, percentages of total lymphocytes (p=0.044), T and B lymphocytes (p=0.004, respectively) were significantly decreased compared to our neonates of healthy mothers. By subdividing the group of neonates in offspring of mothers with IDDM (n=15) or gestational diabetes (n=7), differences compared to normal neonates were mainly observed in neonates of mothers with IDDM (T lymphocytes: p=0.006; B lymphocytes: p=0.008). In cord blood, 45.5% of neonates had antibodies to islet cells, insulin or glutamic acid decarboxylase, most likely transmitted through the placenta of the diabetic mother. No association was found between alterations of lymphocyte subsets and antibody-positivity in cord blood, nor was there any correlation of lymphocyte counts and mean HbA1 during pregnancy, maternal age at delivery, diabetes duration, or neonatal birth weight, respectively. Comparisons among age groups from newborn infants through adolescents revealed higher percentages of total lymphocytes and lower percentages of activated T cells in children of diabetic mothers compared to children of the reference population between the age of 1 to 6 years (67–73% of the cases above and 62–77% below the interquartiles of the reference range, respectively). No significant differences in lymphocyte subpopulations between children of mothers with IDDM diabetes and gestational diabetes have been detected. In addition, there were no abnormalities of lymphocyte subsets in children who are at high risk for the development of IDDM. In summary, we suggest that the observed changes in children of diabetic mothers may reflect a cellular immune reaction to the particular maternal environment, characterized by both an abnormal metabolic state and persisting autoimmunity in the affected mother.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418377
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  • 2
    Electronic Resource
    Electronic Resource
    Alterations of lymphocyte subsets in children of diabetic mothers (1994)
    Springer
    Diabetologia 37 (1994), S. 1132-1141 
    Details
    ISSN: 1432-0428
    Keywords: Key words Lymphocyte subsets ; insulin-dependent diabetes mellitus ; gestational diabetes ; cord blood.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the impact of diabetic mothers on the maturation of the immune system in their offspring, immunophenotypic markers of major lymphocyte subpopulations were evaluated by two-colour flow cytometric analysis in 160 healthy children of diabetic mothers (100 with insulin-dependent diabetes mellitus (IDDM); 48 with gestational diabetes), including 22 neonates, 45 infants aged 8–12 months, 46 children aged 1–2 years, 29 children aged 3–6 years and 18 children aged 7–17 years. Results were compared with 21 neonates of healthy mothers from our hospital and with 110 paediatric subjects of a reference population. In neonates of diabetic mothers, percentages of total lymphocytes (p = 0.044), T and B lymphocytes (p = 0.004, respectively) were significantly decreased compared to our neonates of healthy mothers. By subdividing the group of neonates in offspring of mothers with IDDM (n = 15) or gestational diabetes (n = 7), differences compared to normal neonates were mainly observed in neonates of mothers with IDDM (T lymphocytes: p = 0.006; B lymphocytes: p = 0.008). In cord blood, 45.5 % of neonates had antibodies to islet cells, insulin or glutamic acid decarboxylase, most likely transmitted through the placenta of the diabetic mother. No association was found between alterations of lymphocyte subsets and antibody-positivity in cord blood, nor was there any correlation of lymphocyte counts and mean HbA1 during pregnancy, maternal age at delivery, diabetes duration, or neonatal birth weight, respectively. Comparisons among age groups from newborn infants through adolescents revealed higher percentages of total lymphocytes and lower percentages of activated T cells in children of diabetic mothers compared to children of the reference population between the age of 1 to 6 years (67–73 % of the cases above and 62–77 % below the interquartiles of the reference range, respectively). No significant differences in lymphocyte subpopulations between children of mothers with IDDM diabetes and gestational diabetes have been detected. In addition, there were no abnormalities of lymphocyte subsets in children who are at high risk for the development of IDDM. In summary, we suggest that the observed changes in children of diabetic mothers may reflect a cellular immune reaction to the particular maternal environment, characterized by both an abnormal metabolic state and persisting autoimmunity in the affected mother. [Diabetologia (1994) 37: 1132–1141]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418377
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  • 3
    Electronic Resource
    Electronic Resource
    On the appearance of islet associated autoimmunity in offspring of diabetic mothers: a prospective study from birth (1993)
    Springer
    Diabetologia 36 (1993), S. 402-408 
    Details
    ISSN: 1432-0428
    Keywords: Islet cell antibodies ; insulin autoantibodies ; autoimmunity ; mother-offspring-study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For the first time the incidence of insulin autoantibodies and islet cell antibodies were evaluated in a prospective study from birth. Consecutive neonates (168) from mothers with Type 1 (insulin-dependent) diabetes mellitus (n=113) and gestational diabetes (n=55) were included at birth. To date, follow-up sera were obtained from 90 of 168 mother-child-pairs 9 months postpartum and from 39 of 168, 2 years postpartum. At birth, there was a strong correlation between the presence of antibodies in the cord blood of neonates and in maternal circulation [Type 1 diabetic mothers: 20% islet cell antibodies ≥20 JDF-U (detection threshold of our islet cell antibody assay), 74% insulin antibodies 〉49 nU/ml (upper limit of normal range in sera of healthy control subjects aged 0.5 to 46 years); neonates: 21% islet cell antibodies ≥20 JDF-U, 76% insulin antibodies 〉49 nU/ml; gestational diabetic mothers: 11% islet cell antibodies ≥20 JDF-U, 18% insulin antibodies 〉49 nU/ml; neonates: 13% islet cell antibodies ≥20 JDF-U, 55% insulin antibodies 〉49 nU/ml]. This supports transplacental passage of insulin antibodies and islet cell antibodies from diabetic mothers to their offspring. During follow-up, the majority of children lost antibody-positivity after birth. A few offspring, however, exhibited or developed antibodies consistently, whereby insulin autoantibodies preceded islet cell antibodies in each case (antibody-positivity: 9 months: 0% islet cell antibody positive, 3.3% insulin autoantibody positive; 2 years: 2.6% islet cell antibody positive, 7.7% insulin autoantibody positive). Persisting antibody-positivity in follow-up samples of offspring of diabetic mothers was significantly correlated with older maternal age at delivery (median 38 vs 28 years, p〈0.001). It is concluded that antibodies are common in cord blood of neonates of mothers with Type 1 and gestational diabetes, but they normally disappear after birth. In several children, however, islet cell autoimmunity is detected at very young age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402275
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  • 4
    Electronic Resource
    Electronic Resource
    Development of celiac disease-associated antibodies in offspring of parents with Type I diabetes (2000)
    Springer
    Diabetologia 43 (2000), S. 1005-1011 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Celiac disease ; Type I diabetes ; transglutaminase ; antibody screening ; islet antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The aim of this study was to determine the frequency and temporal development of antibodies related to celiac disease in offspring of parents with Type I (insulin-dependent) diabetes mellitus. Methods. Sera from 913 offspring of parents with Type I diabetes prospectively followed from birth to the age of 8 years were tested for IgG-transglutaminase antibodies (IgG-tTGCAs), endomysial IgA antibodies (EMA) and gliadin antibodies. Results. We found tTGCAs in 32 (3.5 %) of the 913 relatives. Prevalence was related to age and reached 6.5 % at age 8 years. Endomysial IgA antibodies were detected in 44 % of the relatives with tTGCAs and 0.6 % of tTGCA negative relatives and were also most prevalent (5 %) in those aged 8 years. Both tTGCAs and EMAs were more frequent in relatives with the HLA DRB1*03 DQA1*0501 DQB1*02 haplotype (7.1 % and 7.2 %, respectively; p 〈 0.005). Anti-gliadin antibodies were common in both tTGCA positive (42 %) and negative (23 %) relatives, did not show a relation with age and were less prevalent in relatives with HLA DR3 (p 〈 0.05). There was no association between the presence of antibodies associated with celiac disease and islet autoantibodies in these relatives. Of the relatives 15 (1.6 %) had tTGCAs plus EMAs. In two of these, anti-gliadin antibodies were detected before the detection of tTGCAs and EMAs at the age of 9 months whereas none of the remainder had any antibodies associated with celiac disease before age 2 years. In three there were no detectable anti-gliadin antibodies in any of the samples tested. Celiac disease without clinical symptoms was diagnosed in 9 of 12 by intestinal biopsy. Conclusion/interpretation. A statistically significant proportion of relatives of patients with Type I diabetes have celiac disease-associated autoimmunity and the silent form of celiac disease early in life. These relatives should, therefore, be considered for celiac antibody screening. [Diabetologia (2000) 43: 1005–1011]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051483
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  • 5
    Electronic Resource
    Electronic Resource
    Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic dysinnervation in newly diagnosed and long-term IDDM patients (1996)
    Springer
    Diabetologia 39 (1996), S. 970-975 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; metaiodobenzylguanidine ; autonomic neuropathy ; nervous tissue autoantibodies ; islet cell antibodies.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the presence of autoantibodies against sympathetic nervous tissue and their correlation with cardiac sympathetic dysinnervation in insulin-dependent diabetes mellitus (IDDM), 20 newly diagnosed (age 26 ± 6 years) and 48 long-term IDDM patients (age 40 ± 13 years, duration of diabetes 22 ± 12 years) without myocardial perfusion abnormalities (normal 99 mTC-methoxyisobutylisonitrile uptake) were assessed for myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake and complement-fixing sympathetic ganglia (CF-SG) autoantibodies. Both groups of patients were also studied for islet cell antibodies (ICA) and ECG-based cardiac autonomic neuropathy. Eighty control subjects (age 18–49 years) were investigated for CF-SG autoantibodies. Eight newly diagnosed (40 %) and 12 long-term (25 %) IDDM patients exhibited CF-SG autoantibodies, compared to 4 control subjects (5 %; p 〈 0.01, p 〈 0.05). In long-term diabetic patients, the reduction of global but not of regional myocardial 123I-MIBG uptake correlated with CF-SG autoantibodies (r = 0.34, p = 0.02). Newly diagnosed diabetic patients did not show an association between CF-SG autoantibodies and global or regional myocardial 123I-MIBG uptake. ECG-based cardiac autonomic neuropathy ( ≥ two of five cardiac reflex tests abnormal) was present in 22 and absent in 26 long-term IDDM patients, of whom 9 (41 %) and 3 (12 %), respectively were positive for CF-SG autoantibodies (p = 0.02). Only 1 newly diagnosed IDDM patient demonstrated ECG-based cardiac autonomic neuropathy and was also positive for CF-SG autoantibodies. Although they are somewhat suggestive, results concerning autoantibodies against sympathetic nervous tissue and cardiac sympathetic dysinnervation do not strongly support the view that autoimmune mechanisms play a major role in the pathogenesis of cardiac sympathetic neuropathy in IDDM. [Diabetologia (1996) 39: 970–975]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403917
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  • 6
    Electronic Resource
    Electronic Resource
    Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic dysinnervation in newly diagnosed and long-term IDDM patients (1996)
    Springer
    Diabetologia 39 (1996), S. 970-975 
    Details
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; metaiodobenzylguanidine ; autonomic neuropathy ; nervous tissue autoantibodies ; islet cell antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the presence of autoantibodies against sympathetic nervous tissue and their correlation with cardiac sympathetic dysinnervation in insulin-dependent diabetes mellitus (IDDM), 20 newly diagnosed (age 26±6 years) and 48 long-term IDDM patients (age 40±13 years, duration of diabetes 22±12 years) without myocardial perfusion abnormalities (normal 99mTC-methoxyisobutylisonitrile uptake) were assessed for myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake and complement-fixing sympathetic ganglia (CF-SG) autoantibodies. Both groups of patients were also studied for islet cell antibodies (ICA) and ECG-based cardiac autonomic neuropathy. Eighty control subjects (age 18–49 years) were investigated for CF-SG autoantibodies. Eight newly diagnosed (40%) and 12 long-term (25%) IDDM patients exhibited CF-SG autoantibodies, compared to 4 control subjects (5%; p〈0.01, p〈0.05). In long-term diabetic patients, the reduction of global but not of regional myocardial 123I-MIBG uptake correlated with CF-SG autoantibodies (r=0.34, p=0.02). Newly diagnosed diabetic patients did not show an association between CF-SG autoantibodies and global or regional myocardial 123I-MIBG uptake. ECG-based cardiac autonomic neuropathy (≥ two of five cardiac reflex tests abnormal) was present in 22 and absent in 26 long-term IDDM patients, of whom 9 (41%) and 3 (12%), respectively were positive for CF-SG autoantibodies (p=0.02). Only 1 newly diagnosed IDDM patient demonstrated ECG-based cardiac autonomic neuropathy and was also positive for CF-SG autoantibodies. Although they are somewhat suggestive, results concerning autoantibodies against sympathetic nervous tissue and cardiac sympathetic dysinnervation do not strongly support the view that autoimmune mechanisms play a major role in the pathogenesis of cardiac sympathetic neuropathy in IDDM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403917
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  • 7
    Electronic Resource
    Electronic Resource
    Delay of Type I diabetes in high risk, first degree relatives by parenteral antigen administration: the Schwabing Insulin Prophylaxis Pilot Trial (1998)
    Springer
    Diabetologia 41 (1998), S. 536-541 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type I (Insulin-dependent) diabetes mellitus ; intervention ; prevention ; autoantibodies ; insulin-prophylaxis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Schwabing Insulin Prophylaxis Trial is a randomised, controlled pilot study designed to examine whether insulin therapy can delay or prevent the clinical onset of Type I diabetes in high risk first degree relatives of people with the disease. First degree relatives of patients with Type I diabetes, who were aged 4 years or more, had an islet cell antibody (ICA) value more than 20 Junevile Diabetes Foundation Units (JDF-U), a reduced first phase insulin response (FPI) to an i. v. glucose tolerance test less than the 5th centile, and a normal oral glucose tolerance test were eligible for the trial. Between January 1989 and October 1995, 1736 relatives of patients with Type I diabetes were screened for ICA. We identified 64 cases (3.7 %) with ICA values more than 20 JDF-U. Of ICA positive relatives, 17 (27 %) had a low FPI and were eligible for enrolment. Of these 14 agreed to participate, of whom 7 were randomised to the treatment group and 7 to the control group. In the treatment group, human insulin was administered i. v. by continuous infusion for 7 days, followed by daily s. c. injections for 6 months. Intravenous insulin infusions were repeated every 12 months. In the treatment group 3 of the 7 individuals (follow-up from time of eligibility: 2.3 to 7.1 years) and in the control group 6 of the 7 untreated individuals (1.7 to 7.1 years) developed clinical diabetes. Life table analysis showed that clinical onset of Type I diabetes was delayed in insulin-treated subjects compared with control subjects (means ± SEM diabetes-free survival: 5.0 ± 0.9 years vs 2.3 ± 0.7 years, p 〈 0.03). Insulin levels after i. v. glucose increased in the first year of intervention therapy. Titres of ICA, and antibodies to glutamic acid decarboxylase, and tyrosine phosphatase-like protein IA2 remained unchanged. These data suggest that insulin prophylaxis can delay the onset of overt diabetes in high risk relatives. This is encouraging in view of 1) the continuing American Diabetes Prevention Trial, which is currently testing the effect of parenteral insulin in a large nation-wide study and 2) the initiation of pilot trials to determine whether new antigen-specific intervention is more effective in delaying the clinical onset of Type I diabetes. [Diabetologia (1998) 41: 536–541]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050943
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  • 8
    Electronic Resource
    Electronic Resource
    Comparison of a novel micro-assay for insulin autoantibodies with the conventional radiobinding assay (1998)
    Springer
    Diabetologia 41 (1998), S. 681-683 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin autoantibodies ; radiobinding assay ; prediction ; insulin-dependent diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Measurement of insulin autoantibodies (IAA) with a novel micro radiobinding assay which requires only 20 μl of serum was compared with that in a conventional radiobinding assay which uses 600 μl of serum. IAA were measured with both assays in samples from 94 new onset insulin-dependent diabetes mellitus (IDDM) patients, 97 control subjects, and 48 first degree relatives of IDDM patients selected for having IAA in the conventional radiobinding assay. Overall, 227 (95 %) of 239 samples tested were concordant, and IAA levels correlated well (r 2 = 0.7) between the two assays. Discordant results were obtained in 7 new onset patients, 4 control subjects, and 1 first degree relative, and these had low IAA levels in the respective assays. Sensitivity and specificity in the new onset IDDM patients and control subjects were 69 % and 98 % for the micro radiobinding assay and 72 % and 98 % for the conventional radiobinding assay. The use of the micro radiobinding assay should greatly facilitate islet related antibody screening, particularly in children. [Diabetologia (1998) 41: 681–683]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050968
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  • 9
    Electronic Resource
    Electronic Resource
    Influence of diabetes mellitus on the heart and macrovascular mortality (1997)
    Springer
    Diabetologia 40 (1997), S. S125 
    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/s001250051426
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  • 10
    Electronic Resource
    Electronic Resource
    Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with Type I diabetes: The German BABYDIAB study (1999)
    Springer
    Diabetologia 42 (1999), S. 671-677 
    Details
    ISSN: 1432-0428
    Keywords: Keywords HLA genotype ; Type I diabetes ; islet autoimmunity ; autoantibody appearance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Islet autoantibodies precede the clinical onset of Type I (insulin-dependent) diabetes mellitus. The cumulative development of such autoantibodies in infants followed from birth and in particular infants with high-risk HLA genotypes is poorly defined, but such information is essential to design trials to prevent islet autoimmunity. Methods. HLA genotypes were determined in offspring of parents with Type I diabetes who were followed from birth for at least 2 years (median follow-up: 3.1 years) and who were characterised for the expression of insulin, GAD65, IA-2 and islet cell autoantibodies at birth, 9 months, 2 and 5 years of age. Results. The HLA genotypes DRB1 * 03/04(DQB1 *57non-Asp) and DRB1 * 04/04(DQB1*57non-Asp) were present in 7.1 % and 5.0 % of offspring of parents with Type I diabetes. The frequency of both genotypes was increased in offspring who developed islet autoantibodies within the first 2 years of life (27.3 % vs 5.5 %, odds ratio 6.3 [p = 0.002] and 22.7 % vs 4.2 %, odds ratio 6.6 [p = 0.003]) and half of all offspring who developed antibodies had these genotypes. Other genotypes were not associated with an increase in risk. By life-table analysis, the cumulative risk of developing islet autoantibodies by the age of 2 years was 20 % (95 % CI 9.4,30.6) for offspring carrying either the DRB1 * 03/04(DQB1 *57non-Asp) or the DRB1 * 04/04(DQB1*57non-Asp) genotype compared with 2.7 % (95 % CI 1.2,4.2) for offspring without these genotypes (p 〈 0.0001). Conclusion/interpretation. These data show that early appearance of islet autoantibodies is remarkably frequent for DR3/4 heterozygous and DR4/4 homozygous offspring and indicate that primary prevention could be considered once available in an offspring cohort selected for these genotypes. [Diabetologia (1999) 42: 671–677]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051214
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