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  • 1
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Twenty diabetics were treated over a period of eight days with hydrochlorothiazide and for other eight days with hydrochlorothiazide and thiamine. The thiazide-induced hyperglycemia was significantly decreased by the additional therapy with thiamine to the original values before hydrochlorothiazide treatment started (p〈0,05). The fasting levels of seruminsulin (IRI) after hydrochlorothiazide treatment (with and without thiamine) were somewhat higher than the levels before (p〈0,1). Free fatty acids and phosphate in plasma did not change. The results suggest an extrapancreatic mechanism for hydrochlorothiazide-induced hyperglycemia. Antagonistic action of thiamine and thiazide could be an important factor of hydrochlorothiazide influence on carbohydrate metabolism.
    Notes: Zusammenfassung 20 Diabetikern wurde 8 Tage lang Hydrochlorothiazid und über weitere 8 Tage zusätzlich Thiamin verabreicht. Die durch Hydrochlorothiazid signifikant herabgesetzte Glucosetoleranz normalisierte sich nach zusätzlichen Thiamingaben. Die Nüchternwerte des Seruminsulins (IRI) waren unter Thiazidgaben (mit und ohne Thiamin) gegenüber den Ausgangswerten ohne Thiazidbelastung erhöht (p〈0,1). Freie Fettsäuren und anorganisches Phosphat im Plasma blieben unverändert. Die erhobenen Befunde sprechen für extrapankreatische Faktoren als Ursache der durch Saluretica verursachten Stoffwechselstörung. Ein Thiamin-Thiazid-Antagonismus könnte nach unseren Versuchsergebnissen ein Faktor im möglicherweise komplex beeinflußten Stoffwechsel von „Thiaziddiabetikern“ sein.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Blutlaktat ; Buformin ; Diabetes ; Dichlorazetat ; Blood lactate ; buformin ; diabetes ; dichloroacetate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In animals, dichloroacetate (DCA) which activates pyruvate dehydrogenase has been shown to diminish increased blood lactate concentrations due to biguanide treatment. In 10 maturity onset diabetics, therefore, the effect of a combined therapy with buformin and DCA (200 mg b.i.d.) was studied on blood lactate concentrations and compared with an analogous pre- and postinvestigation period of 6 days with buformin treatment alone (100 mg b.i.d.). Mean blood glucose concentrations remained the same during all 3 investigation periods. Also, neither fasting nor postprandially significant differences were found in blood lactate and ketones. In association with a standardized ergometer test, however, the rise in blood lactate was significantly smaller (p〈0.05) while the patients were on buformin plus DCA, compared to the periods when only buformin was given. Furthermore, less ketone bodies appeared to be utilized by the exercising muscle under the influence of the combined treatment (p〈0.05). These results are in good agreement with animal studies and suggest that DCA might be as effective in decreasing enhanced blood lactate concentrations in biguanide treated man as in animals.
    Notes: Zusammenfassung Im Tierversuch vermag Dichlorazetat (DCA), das die Pyruvatdehydrogenase stimuliert, erhöhte Blutlaktatspiegel unter Biguaniden zu senken. Bei 10 Erwachsenendiabetikern wurde daher der Einfluß einer Kombinationsbehandlung mit Buformin und DCA (400 mg tgl.) auf die Blutlaktatspiegel untersucht und mit einer analogen Vor- und Nachperiode einer alleinigen Buforminbehandlung (200 mg tgl.) über 6 Tage verglichen. Die Diabeteseinstellung blieb gemessen an den mittleren Blutglucosekonzentrationen während der 3 Untersuchungsperioden unverändert. Ebenfalls keine signifikanten Unterschiede, weder nüchtern noch postprandial, ergaben sich hinsichtlich der Laktat-und Ketonkörperspiegel im Blut. Im Anschluß an einen standardisierten Ergometertest jedoch stieg unter der Kombinationstherapie mit Buformin und DCA das Blutlaktat wesentlich geringer an (p〈0,05) als unter Buformin allein. Gleichzeitig wurden unter der Kombinationstherapie weniger Ketonkörper vom arbeitenden Muskel utilisiert (p〈0,05). Diese Ergebnisse stimmen mit Tierversuchen gut überein und können im Sinne einer vermehrten Pyruvatoxidation unter DCA interpretiert werden; es ist zu hoffen, daß DCA ähnlich wie beim Tier auch bei biguanidbehandelten Diabetikern einem excessiven Ansteigen der Blutlaktatspiegel vorbeugen kann.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Type I diabetes ; Autoimmunity ; Ia-antigen bearing cells ; ICA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 47 (1969), S. 721-722 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    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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  • 7
    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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  • 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.
    Type of Medium: Electronic Resource
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  • 9
    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
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  • 10
    ISSN: 1432-0428
    Keywords: Keywords Non-insulin-dependent diabetes mellitus ; mortality ; macrovascular mortality ; von Willebrand-factor ; urine albumin excretion ; HbA1c ; blood pressure ; lipids.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The 10-year follow-up of the Munich General Practitioner Project was designed as a long-term prospective study to evaluate factors predicting macrovascular and overall mortality in a random cohort of non-insulin-dependent diabetic (NIDDM) patients. Of the original 290 patients (103 males, 187 females, median age 65 years) 92.5 % could be assessed, 103 subjects had died, 58 from macrovascular causes. In an univariate analysis of baseline data, deceased patients, and especially those who died from macrovascular causes had significantly higher fasting blood glucose, HbA1c, von Willebrand-factor protein, urine albumin excretion, and serum β 2-microglobulin, were significantly older, exhibited significantly more ischaemic heart disease (abnormal ECG Minnesota codes), carotid artery and peripheral vascular disease (both determined by ultrasound-Doppler), and had significantly inferior knowledge about diabetes and its treatment. No significant differences were seen for gender, blood pressure, smoking, total cholesterol, triglycerides, HDL-cholesterol, or the use of antidiabetic, antihypertensive or coronary drugs. In a multiple logistic regression analysis, the risk factors for macrovascular death were age, HbA1c and von Willebrand-factor protein. When baseline macrovascular disease was taken into account, carotid artery disease was also a determinant. The main variables from the metabolic syndrome (blood pressure, dyslipidaemia, body mass index) did not enter a multiple logistic regression analysis. The data suggest that age and haemoglobin A1c are major determinants, and that in addition von Willebrand-factor associated endothelial damage is a risk factor for macrovascular mortality in NIDDM patients. [Diabetologia (1996) 39: 1540–1545]
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