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  • 1
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; metaiodobenzylguanidine ; autonomic neuropathy ; sympathetic dysinnervation ; QT interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To analyse the presence and extent of global and regional distributions of cardiac sympathetic dysinnervation in long-term insulin-dependent diabetes mellitus (IDDM) without myocardial perfusion abnormalities (99mTc-methoxy isobutyl isonitrile study), 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy was performed in two clinically-comparable groups (20 diabetic patients with and 22 diabetic patients without ECG-based cardiac autonomic neuropathy). For comparison nine control subjects without heart disease were investigated. Only six diabetic patients (27%) without and one diabetic patient (5%) with ECG-based autonomic neuropathy were found to have a uniform homogeneous uptake of 123I-MIBG, in contrast to a uniform homogeneous uptake in all control subjects. The uptake of 123I-MIBG in the posterior myocardium of diabetic patients was smaller than in the anterior, lateral and septal myocardium (p〈0.001, p〈0.001, p=0.001). In addition, diabetic patients with cardiac autonomic neuropathy (≥ two of five age-related cardiac reflex tests abnormal) demonstrated a more reduced uptake in the global, lateral and posterior myocardium than diabetic patients without (p〈0.01, p〈0.01, p〈0.001). A correlation between global or regional myocardial 123I-MIBG uptake, however, and duration of diabetes, HbA1c, body mass index or QT interval length was not observed. Our study demonstrates that cardiac sympathetic dysinnervation is common in long-term IDDM even in patients without ECG-based cardiac autonomic neuropathy and that the posterior myocardium is predominantly affected. We conclude that 123I-MIBG scintigraphy is a promising approach to further elucidate the pattern and natural history of myocardial dysinnervation in IDDM.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Key words Insulin-dependent diabetes mellitus ; metaiodobenzylguanidine ; autonomic neuropathy ; sympathetic dysinnervation ; QT interval.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To analyse the presence and extent of global and regional distributions of cardiac sympathetic dysinnervation in long-term insulin-dependent diabetes mellitus (IDDM) without myocardial perfusion abnormalities (99 mTc-methoxy isobutyl isonitrile study), 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy was performed in two clinically-comparable groups (20 diabetic patients with and 22 diabetic patients without ECG-based cardiac autonomic neuropathy). For comparison nine control subjects without heart disease were investigated. Only six diabetic patients (27 %) without and one diabetic patient (5 %) with ECG-based autonomic neuropathy were found to have a uniform homogeneous uptake of 123I-MIBG, in contrast to a uniform homogeneous uptake in all control subjects. The uptake of 123I-MIBG in the posterior myocardium of diabetic patients was smaller than in the anterior, lateral and septal myocardium (p 〈 0.001, p 〈 0.001, p = 0.001). In addition, diabetic patients with cardiac autonomic neuropathy ( ≥ two of five age-related cardiac reflex tests abnormal) demonstrated a more reduced uptake in the global, lateral and posterior myocardium than diabetic patients without (p 〈 0.01, p 〈 0.01, p 〈 0.001). A correlation between global or regional myocardial 123I-MIBG uptake, however, and duration of diabetes, HbA1 c, body mass index or QT interval length was not observed. Our study demonstrates that cardiac sympathetic dysinnervation is common in long-term IDDM even in patients without ECG-based cardiac autonomic neuropathy and that the posterior myocardium is predominantly affected. We conclude that 123I-MIBG scintigraphy is a promising approach to further elucidate the pattern and natural history of myocardial dysinnervation in IDDM. [Diabetologia (1995) 38: 1345–1352]
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 43 (2000), S. 1455-1469 
    ISSN: 1432-0428
    Keywords: Keywords Cardiac sympathetic dysfunction ; autonomic neuropathy ; coronary blood flow reserve ; endothelial activation ; congestive heart failure ; nitric oxide ; protein kinase C ; acute coronary syndrome ; myocardial infarction.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This review discusses some of the mechanisms inherent in diabetes that predispose patients to increased cardiac morbidity and mortality. Single photon emission computerized tomography or photon emission tomography with radioactive labeled analogues of norepinephrine have shown that cardiac sympathetic dysfunction and incompetence are early and also late abnormalities in patients with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus. Furthermore, myocardial blood flow assessment with photon emission tomography has shown that in patients without myocardial perfusion deficits, endothelial-dependent vasodilatation is severely reduced in relation to cardiac sympathetic dysfunction. In addition, signs of endothelial activation have also been found early in patients with Type I and Type II diabetes in whom vascular disease has not been clinically detected. This activation in conjunction with glycaemic control is important in determining macrovascular mortality. Cardiac sympathetic dysfunction is partially restored to normal with near normalisation of glycaemia. Interpretations. Recently unrecognized “subtle” changes predispose the heart to failure, after ischaemia-induced remodelling, and arteriosclerotic plaques to instability and rupture. These changes act in conjunction with effects, driven by hyperglycaemia and diabetes, on the endothelium of large blood vessels, e. g. on nitric oxide release or on protein kinase-C β activation. Meticulous glucose control early on and rapid recompensation of hyperglycaemia in patients with acute coronary syndrome are part of a successful intensive multifactorial approach to prevent the heart in diabetes converting from ailing to failing. [Diabetologia (2000) 43: 1455–1469]
    Type of Medium: Electronic Resource
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  • 4
    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
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  • 5
    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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  • 6
    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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