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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 11 (1975), S. 255-260 
    ISSN: 1432-0428
    Keywords: Bohr effect ; diabetes ; erythrocyte 2,3-DPG ; Hill-coefficient ; ketoacidosis ; oxygen affinity of whole blood ; P50 act pH ; plasma inorganic phosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Daily evaluations of 8 newly detected ketoacidotic diabetics showed the Bohr-effect of haemoglobin to be decreased by 50% while erythrocyte 2,3-DPG was decreased below 10 μmoles/g Hb. 2,3-DPG correlated strongly with pH during acidosis and with plasma inorganic phosphate (Pi) subsequently to the first insulin administration. Oxygen affinity of haemoglobin, measured as P50 act pH, was unchanged in ketoacidosis compared to the time before discharge. After correction of acidosis, however, P50 act pH fell strikingly (p 〈 0.001) and remained decreased up to 7 days depending upon the resynthesis of 2,3-DPG in relation to Pi. The Hill-coefficient n reflecting the slope of the oxygen dissociation curve was diminished in ketoacidosis (p 〈 0.005), and decreased further after pH-normalization (p 〈 0.005). There was a close association of n with 2,3-DPG (p 〈 0.001) and additionally with Pi at 2,3-DPG-levels below 10 μmoles/ g Hb. Based on these findings a decreased erythrocyte oxygen release of one fifth during acidosis and more than one third after pH-correction can be hypothesised. In view of the intimate relation of Pi to the oxygen transport system it is suggested that treatment of ketoacidosis should include Pisubstitution.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 463-469 
    ISSN: 1432-0428
    Keywords: Muscle triglycerides ; muscle glycogen ; insulin dependent diabetes mellitus ; insulin deficiency ; glycaemic control ; non-esterified fatty acids ; glycerol ; exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Muscle triglycerides and glycogen were measured in biopsy specimens of the vastus lateralis muscle before and after 1 h of ergometric exercise at 50 to 60% of maximal capacity (i. e. at a pulse rate during exercise of 180 minus age) in 3 groups of 19 to 35 year old, non-obese male subjects: 10 normals, 10 insulin dependent diabetic patients in relatively good control and 10 poorly controlled insulin dependent diabetic patients in whom insulin was withdrawn 24 h prior to examination. At rest in all subjects muscle triglyceride content was positively correlated with serum triglycerides (p〈0.001) and blood glucose (p〈0.05), resulting in elevated muscle triglyceride stores in the insulin deficient diabetic patients (17.9 ±1.8 μmol/g protein vs. 13.4±1.3 and 9.4±1.2 in the normal subjects and the well controlled diabetic patients; p〈0.05 and 〈0.001). During exercise, utilisation of muscle triglycerides and glycogen were directly related to content at rest (p〈0.001), including the insulin-deprived patients with decreased glycogen. The decrease of muscle fat was associated with a rise in serum glycerol (p〈0.001) and nonesterified fatty acids (p〈0.001) during exercise.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin degrading enzyme activity ; insulin binding ; insulin resistance ; Type 2 diabetes ; erythrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Specific insulin degrading enzyme activity of erythrocytes was determined in relation to erythrocyte insulin binding in 16 healthy subjects, 14 Type 1 (insulin-dependent) and various groups of Type 2 (non-insulin-dependent) diabetic patients (n = 39). Degrading activity was increased in Type 2 diabetic patients on sulphonylureas, as well as in a subgroup with good metabolic control (p〈0.001) and in patients with secondary failure to oral therapy (p〈0.02); degrading activity returned to normal in the latter patients after 1 week of insulin treatment. Highest degrading activity was found in insulintreated, yet insulin-insensitive patients (daily insulin dose 〉80 U). Degrading activity was significantly correlated in healthy subjects both with circulating insulin concentrations and maximal specific insulin binding. In contrast, in Type 2 diabetic subjects, degrading activity was inversely correlated with serum insulin with no apparent association with maximal specific insulin binding except in those patients given 1 week of insulin treatment. High erythrocyte insulin degrading enzyme activity might be a common feature in the insulin-insensitive Type 2 diabetic patient and might occur subsequent to some aspect of insulin deficiency at the tissue level.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 79-80 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Cyclosporin A ; Type 1 (insulin-dependent) diabetes mellitus ; immunotherapy ; C-peptide ; islet function ; remission of Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long-lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. 1132-1141 
    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
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. 1132-1141 
    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
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  • 8
    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.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 461-466 
    ISSN: 1432-0428
    Keywords: Erythrocyte 2.3-DPG ; diabetes ; blood glucose variation ; islet cell tumor ; insulin ; tolbutamide ; microangiopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary No significant differences were found in the erythrocyte 2.3-DPG concentration between 14 normals (16.82±0.66 μmoles 2.3-DPG/g Hb) and 44 diabetic patients (16.22±0.38 μmoles 2.3-DPG/g Hb). However, in diabetic patients we could demonstrate significant fluctuations determined by the metabolic control of their diabetes. Hyperglycaemic patients (n = 10) developed during treatment, concomitant with declining blood glucose, a significant decrease to 13.97± 0.64 [mioles 2.3-DPG/g Hb. After normalization of blood glucose the 2.3-DPG level rose again. Two patients with islet cell tumors had a fluctuation in the 2.3-DPG concentration of about 20%, when symptomatic hypoglycaemia occurred during an extended fast. This variation in 2.3-DPG dependent upon changes in blood glucose was also demonstrated in-vitro by a dialysis technique where glucose was kept constant at 400 or 80 mg/100 ml. Incubating hyperglycaemic blood (n = 6) of uncontrolled diabetics in a high glucose medium, 2.3-DPG was constant over 7 h, whereas at low glucose concentration 2.3-DPG dropped significantly (p 〈 0.001). Blood from nondiabetic subjects did not show this phenomenon. In-vitro additions of insulin and tolbutamide failed to produce an effect on 2.3-DPG. Our results suggest that pronounced fluctuations of blood glucose in diabetics influence 2.3-DPG levels in erythrocytes and thus might impair peripheral oxygen supply.
    Type of Medium: Electronic Resource
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  • 10
    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]
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