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  • 1
    Digitale Medien
    Digitale Medien
    Left ventricular relaxation and filling pattern in diabetic heart muscle disease: An echocardiographic study (1988)
    Springer
    Journal of molecular medicine 66 (1988), S. 773-778 
    Details
    ISSN: 1432-1440
    Schlagwort(e): Diabetic Heart Muscle Disease ; Echocardiography ; Relaxation ; Diastole
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In order to study left ventricular function digitized M-mode-echocardiograms were analyzed. 34 patients with insulin-dependent diabetes mellitus (mean age 37.8 years, mean diabetes history 21.5 years) were compared with 35 healthy individuals (mean age 40.9 years). Only patients with negative exercise-ECG, normal 2-D-echocardiogram and normal systemic arterial blood pressure were enclosed. In diabetics the time-constant Te of free wall endocardial retraction was significantly prolonged (76.8±21.2 ms versus 64.0±7.9 ms in normals, p〈0.005), the dimension change during early diastole (dD DS-ERF) was significantly reduced (54.5±13.1% versus 69.8±9% in normals, p〈0.001) and the dimension change during atrial contraction phase (dD ACP) was significantly enlarged (23.4±14.4% versus 14.3±6.4% in normals, p〈0.001). These data suggest that impaired left ventricular diastolic function can be found in patients with long standing insulin-dependent diabetes mellitus.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01726577
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  • 2
    Digitale Medien
    Digitale Medien
    Cell-Mediated autoimmunity at the onset of insulin-dependent diabetes mellitus (IDDM) (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 546-550 
    Details
    ISSN: 1432-1440
    Schlagwort(e): Type I diabetes ; Autoimmunity ; Ia-antigen bearing cells ; ICA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Peripheral blood lymphocytes have been investigated in 20 newly diagnosed type-I diabetics and 10 healthy subjects using monoclonal antibodies. Mononuclear cells were marked with anti-T-lymphocytes (Leu2, 3, 4, 12) and anti-Ia-antibodies (K14, L243) using indirect immunofluorescence. The percentage of circulating K14- and L243-positive cells was significantly higher in all diabetics than in normal controls. An increase in the number of K14-bearing cells was found in newly diagnosed patients with duration of less than 7 days (n=10) compared with diabetics of longer duration (1 to 8 months;n=10). Using dual-color immunofluorescence with fluorescein-conjugated anti-T-lymphocytes and rhodamin-conjugated anti-Ia-antibodies it was not possible to identify Ia-antigen bearing cells (Ia cells) as helper or suppressor lymphocytes. In addition, there was no significant difference in the number of Ia cells in diabetics with and without islet cell antibodies. It is concluded that there is evidence of activation of cellular immune response in type I diabetes, particularly in the early days of manifestation. However, previous assumptions that Ia cells represent T-cell activation have to be questioned.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01727620
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  • 3
    Digitale Medien
    Digitale Medien
    Wertigkeit einer Antikörperdiagnostik bei Schwangeren mit Gestationsdiabetes zur Prädiktion des manifesten Typ-I-Diabetes postpartum (1998)
    Springer
    Der Gynäkologe 31 (1998), S. 25-30 
    Details
    ISSN: 1433-0393
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Zum Thema Patientinnen mit Gestationsdiabetes haben nicht nur ein deutlich erhöhtes Risiko, nach der Schwangerschaft einen manifesten Typ-II-Diabetes, sondern auch einen Typ-I-Diabetes zu entwickeln. Mit dem Nachweis von β-Zell-Antikörpern, die bis zu 15 Jahre vor der klinischen Manifestation eines Typ-I-Diabetes auftreten, ist es heute möglich, Gestationsdiabetikerinnen mit hohem Risiko für einen Typ-I-Diabetes postpartum bereits während der Schwangerschaft zu identifizieren. Nach den Ergebnissen einer aktuellen, prospektiven deutschen Multizenterstudie, in der 437 Gestationsdiabetikerinnen bei Entbindung auf Inselzellantikörper (ICA), und auf Antikörper gegen Glutamatdecarboxylase (GADA) und Thyrosinphosphatase (IA-2) untersucht wurden, betrug das kumulative Risiko für einen Typ-I-Diabetes 2 Jahre postpartum 6,6 %. Gestationsdiabetikerinnen, die während der Schwangerschaft mit Insulin behandelt wurden, hatten ein deutlich höheres 2-Jahres-Risiko (18 %) als Patientinnen, die nur mit Diät behandelt wurden (1,2 %). Dabei nahm das 2-Jahres-Risiko für einen Typ-I-Diabetes mit der Anzahl der bei Entbindung nachgewiesenen Antikörper zu. Bei nur 1 positiven Antikörper betrug das Risiko für einen Typ-I-Diabetes 17 %, bei 2 positiven Antikörpern 61 %, und bei Nachweis aller 3 Antikörper 84 %. Wird nur mit einem Antikörper gescreent, resultiert eine relativ geringe Sensitivität, die zwischen 34 % (für IA-2A) und 63 % bei einem Screening mit GADA (ICA: 48 %) liegt. Dagegen steigt bei kombiniertem Screening mit 2 Antikörpern die Testsensitivität auf 74 % bei Verwendung von ICA plus GADA und auf 75 %, wenn mit GADA und IA2A getestet wird, wobei letzterer Kombitest einfacher und zeitsparender durchgeführt werden kann. Die vorliegenden Daten zeigen, daß ein Screening von Gestationsdiabetikerinnen auf β-Zell-Antikörper in Deutschland sinnvoll ist, weil damit Patientinnen mit hohem Risiko für einen Typ-I-Diabetes postpartum frühzeitig identifiziert und einer rechtzeitigen Insulin-Therapie zugeführt werden können.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00003080
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  • 4
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Keywords Insulin autoantibodies ; radiobinding assay ; prediction ; insulin-dependent diabetes mellitus.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250050968
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  • 5
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Keywords Celiac disease ; Type I diabetes ; transglutaminase ; antibody screening ; islet antibodies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250051483
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  • 6
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Keywords HLA genotype ; Type I diabetes ; islet autoimmunity ; autoantibody appearance.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250051214
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  • 7
    Digitale Medien
    Digitale Medien
    Influence of diabetes mellitus on the heart and macrovascular mortality (1997)
    Springer
    Diabetologia 40 (1997), S. S125 
    Details
    ISSN: 1432-0428
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250051426
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  • 8
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Keywords Type I (Insulin-dependent) diabetes mellitus ; intervention ; prevention ; autoantibodies ; insulin-prophylaxis.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250050943
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  • 9
    Digitale Medien
    Digitale Medien
    Peptide mapping and characterisation of glycation patterns of the glima 38 antigen recognised by autoantibodies in Type I diabetic patients (2000)
    Springer
    Diabetologia 43 (2000), S. 598-608 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Keywords Type I diabetes ; immunology ; autoantibodies ; target autoantigen ; 38 000 Mr autoantigen ; glima 38 ; proteolytic cleavage ; peptide mapping ; lectin binding ; deglycation.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Aims/hypothesis. Glima 38 is an N-glycated neuroendocrine membrane protein of Mr 38 000, which is recognised by autoantibodies in approximately 20 % of patients with Type I (insulin-dependent) diabetes mellitus. The aim of this study was to characterise the carbohydrate moiety and generate peptide maps of glima 38. Methods. Sera of high immunoreactivity to glima 38 were used to isolate 35-S methionine-labelled protein from βTC-3 cells and a neuronal cell line GT1.7. Tunicamycin was used to inhibit N-glycation of glima 38 and define the core protein. The carbohydrate moiety was characterised for tunicamycin sensitivity, lectin binding and susceptibility to different endoglycosidases. The protein moiety was subjected to digestion by proteases to define peptide maps. Results. The autoreactive epitopes in glima 38 recognised by Type I diabetic sera are conformational and independent of the carbohydrate moiety. Inhibition of N-glycation of glima 38 in vivo, shows a protein core of Mr 22 000 in both pancreatic β-(βTC3) and neuronal (GT1.7) cell lines. The carbohydrate moieties in the two cell types are distinct but contain a similar amount of terminal sialic acid residues and at least five oligosaccharide chains Glima 38 binds Triticum vulgare and Ricinus communis I lectins. Endoproteinase treatment of the Mr 22 000 core protein results in peptides of Mr 4500 and Mr 20 000 with Lys-C, and peptides of Mr 4 000 and Mr 11 000–12 000 with Glu-C/V8 and Asp-N proteases. Conclusion/interpretation. The biochemical properties of glima 38 define it as a new autoantigen in Type I diabetes and provide a basis for its purification. [Diabetologia (2000) 43: 598–608]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250051349
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  • 10
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Islet cell antibodies ; insulin autoantibodies ; autoimmunity ; mother-offspring-study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00402275
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