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  • 1
    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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  • 2
    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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  • 3
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; recent onset of diabetes ; microalbuminuria ; metabolic syndrome ; hypertension ; dyslipoproteinaemia ; peripheral vascular disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Still under debate is the prevalence of microalbuminuria in patients with recently diagnosed Type 2 (non-insulin-dependent) diabetes mellitus and its relation to existing macro-vascular disease and the major vascular risk markers. Hence, from a representative sample of 1512 patients with Type 2 diabetes of varied duration (recruited from 22 nonspecialized medical practices of the Greater Munich Area) 68 (26 males, 42 females) of 71 eligible subjects with a known duration of diabetes of up to 17 weeks and not less than 4 weeks were examined in the present study. Median age was 61 (39 to 75) years, prevalence of ischaemic heart disease (case history plus ECG, Minnesota code, Whitehall criteria) 41.2%, and that of peripheral vascular and carotid artery disease (both assessed by ultrasound-Doppler) were 35.3 and 4.4%, respectively. Diabetes was well controlled (HbA1c: 6.9%, 5.6–8.3; fasting blood glucose: 7.7 mmol/l, 5.4–10.4; median±interquartile range IQ), the cardiovascular risk profile was most prominent in terms of triglycerides (3.1 mmol/l, 2.1–4.6, median±IQ range) and systolic blood pressure (164 mm Hg, 140–186, median±IQ range). 13.2% showed signs of urinary tract infection. Of the remainder, 19.0% exhibited microalbuminuria (RIA, 〉30–200 mg/l), and 5.2% macroalbuminuria (〉200 mg/l). Significant correlations (p〈0.05) were found between urinary albumin concentration and β2-microglobubin in serum, systolic blood pressure, serum triglycerides, serum HDL-cholesterol (inversely), HbA1c, and peripheral vascular disease. The results suggest a high prevalence of increased urinary albumin excretion in recently diagnosed Type 2 diabetic patients and a close relationship with several hallmarks of the so-called metabolic syndrome, probably operative in the pre-clinical state of Type 2 diabetes. Based on these observations, increased albuminuria could be a marker of early and accelerated atherosclerosis.
    Type of Medium: Electronic Resource
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  • 4
    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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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    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]
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  • 10
    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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