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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Adhesion molecules ; endothelium ; vascular cell adhesion molecule-1 ; oxidants.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To assess in vivo effects of antioxidants on vascular cell adhesion molecule (VCAM)-1 expression, circulating soluble VCAM-1 and intraerythrocytic reduced glutathione (GSH) and GSH disulphide (GSSG) concentrations were evaluated in non-insulin-dependent diabetic patients without complications (9 men, 6 women, 48 ± 6 years old) before and after 1 month of either oral N-acetyl-L-cysteine (1.200 mg/day) or placebo treatments, given in randomized, cross-over, double-blind fashion. Ten healthy subjects (7 men, 3 women, 52 ± 4 years old) served as control subjects. Baseline plasma VCAM-1 concentrations were higher (p = 0.007) in non-insulin-dependent diabetic patients (707.9 ± 52.5 ng/ml) than in control subjects (627.3 ± 84.6 ng/ml). Intraerythrocytic GSSG content was higher (non-insulin dependent diabetic patients: 0.618 ± 0.185 μmol/g Hb; control subjects: 0.352 ± 0.04 μmol/g Hb, p = 0.0002), whereas intraerythrocytic GSH concentrations were lower (p = 0.001) in non-insulin dependent diabetic patients (6.0 ± 0.7 μmol/g Hb) than in control subjects (7.1 ± 0.5 μmol/g Hb). The mean GSH:GSSG ratio was also lower (p = 0.0001) in the first (10.9 ± 4.5) than in the second group (20.2 ± 1.4). Circulating VCAM-1 and intraerythrocytic GSH concentrations were negatively correlated in non-insulin diabetic patients (r = 0.605, p = 0.01). Treatment with N-acetyl-L-cysteine decreased plasma VCAM-1 (p = 0.01) and intraerythrocytic GSSG (p = 0.006) but increased GSH concentrations (p = 0.04) and the GSH:GSSG ratio (p = 0.004) in non-insulin dependent diabetic patients. Our data indicate that the vascular endothelium is activated in non-insulin dependent diabetes. Antioxidant treatment counterbalanced such endothelial activation. Thus, antioxidant agents might protect against oxidant-related upregulation of endothelial adhesion molecules and slow down the progression of vascular damage in non-insulin dependent diabetes. [Diabetologia (1998) 41: 1392–1396]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; oral insulin ; insulin antibodies ; prevention.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Induction of tolerance to insulin is achievable in animal models of Type I (insulin-dependent) Diabetes mellitus by oral treatment with this hormone, which can lead to prevention of the disease. In the Diabetes Prevention Trial of Type I diabetes (DPT-1), oral insulin is given with the aim of preventing disease insurgence. We investigated whether if given at diagnosis of Type I diabetes in humans, oral insulin can still act as a tolerogen and therefore preserve residual beta-cell function, which is known to be substantial at diagnosis. Methods. A double-blind trial was carried out in patients (mean age ± SD: 14 ± 8 years) with recent-onset Type I diabetes to whom oral insulin (5 mg daily) or placebo was given for 12 months in addition to intensive subcutaneous insulin therapy. A total of 82 patients with clinical Type I diabetes ( 〈 4 weeks duration) were studied. Basal C peptide and glycated haemoglobin were measured and the insulin requirement monitored every 3 months up to 1 year. Insulin antibodies were also measured in 27 patients treated with oral insulin and in 18 patients receiving placebo at the beginning of the trial and after 3, 6 and 12 months of treatment. Results. The trial was completed by 80 patients. Overall and without distinction between age at diagnosis, at 3, 6, 9 and 12 months baseline mean C-peptide secretion in patients treated with oral insulin did not differ from that of those patients treated with placebo. In patients younger than 15 years a tendency for lower C-peptide values at 9 and 12 months was observed in the oral insulin group. Insulin requirement at 1 year was similar between the two groups as well as the percentage of glycated haemoglobin. Finally, IgG insulin antibodies were similar in the two groups at each time point. Conclusion/interpretation. The results of this study indicate that the addition of 5 mg of oral insulin does not modify the course of the disease in the first year after diagnosis and probably does not statistically affect the humoral immune response against insulin. [Diabetologia (2000) 43: 1000–1004]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-5233
    Keywords: Blood pressure ; Nycthermal rhythm ; Diabetic autonomic neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of our study was to analyse the 24-h periodic pattern of blood pressure (BP) in diabetic patients with abnormal responses to cardiovascular reflexes, in order to evaluate the extent of the initial autonomic damage. We studied 44 patients with diabetes mellitus (14 insulin-dependent, 30 non-insulin-dependent; mean duration of disease 6.5±1.8 years) in good metabolic control (fasting glycaemia 〈140 mg/dl, postprandial glycaemia 〈180 mg/dl, fructosamine 〈285 mg/dl), divided into two subgroups, containing 21 normotensives (13 males and 8 females aged 28–72 years) and 23 hypertensives (13 males and 10 females aged 32–70 years) respectively. All patients showed abnormal responses to at least two out of four tests: deep breathing, lying to standing, Valsalva manœuvre and postural hypotension. Two sex-and age-matched control groups were recruited, comprising 20 normotensive and 20 hypertensive diabetic patients without dysautonomia, respectively. The reference group consisted of 248 normotensives (135 males and 113 females, aged 18–76 years) and 212 mild-moderate hypertensives (130 males and 82 females, aged 27–66 years). Each patient underwent ambulatory BP monitoring for at least 24 h, using an auscultatory automatic device. Data concerning biological rhythms were analysed by means of periodic functions. We limited the Fourier partial sums to the first three harmonics. In the diabetic normotensive groups, we observed that the absolute systolic and diastolic BP minima during the night occurred very rapidly and that the increase to the morning maximum was markedly slowed in patients with abnormal responses to cardiovascular tests in comparison with the controls (nocturnal BP decrease −5.8/−4.7 vs −3.8/−4.0 mm Hg/h; increase 4.7/3.6 vs 5.9/6.1 mm Hg/h). The same phenomenon was observed in both hypertensive groups but the differences were more marked (nocturnal BP decrase −7.7/−7.1 vs −4.3/−3.9 mm Hg/h; increase 3.2/2.1 vs 5.8/4.3 mm Hg/h). Diabetic patients without dysautonomia had similar patterns to those in the normotensive and hypertensive reference groups. Since alterations in circadian rhythm are preceded by an intermediate smoothed BP curve during the early morning, which is well defined by Fourier analysis and related “speeds”, this method makes it possible to quantify the extent of the initial autonomic damage.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1619-1560
    Keywords: Blood pressure ; Circadian rhythm ; Fourier series ; Dysautonomia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The 24 h periodic pattern of blood pressure was studied in 44 patients with diabetes mellitus (14 type 1, 30 type 2; mean duration of disease 6.5 ± 1.8 years) in good metabolic control but with abnormal cardiovascular reflex responses; of these 21 were normotensive and 23 hypertensive. All had abnormal responses to at least two out of four tests: deep breathing, lying to standing, Valsalva manoeuvre and postural hypotension. Two sex- and agematched groups, consisting of 20 normotensive and 20 hypertensive diabetic patients without dysautonomia, were studied as controls. Each patient underwent ambulatory blood pressure monitoring for at least 24 h, using an auscultatory automatic device. Data were analysed using the sum of three periodic functions (Fourier partial sum). In the diabetic normotensive groups, the absolute blood pressure fell to its night-time minimum more rapidly, and increased to its morning maximum more slowly, in those with abnormal cardiovascular reflexes than in the controls (nightly blood pressure decrease −5.8/−4.7 vs. −3.8/−4.0 mmHg/h; increase 4.7/3.6 vs. 5.9/6.1 mmHg/h). The same behaviour was found in both hypertensive groups but the amplitude of the differences was more marked (blood pressure nocturnal decrease −7.7/−7.1 vs. −4.3/−3.9 mmHg/h; increase 3.2/2.1 vs. 5.8/4.3 mmHg/h). This analysis of 24 h ambulatory blood pressure data may be of value in diagnosis and evaluation of autonomic deficits.
    Type of Medium: Electronic Resource
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