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  • 1
    Electronic Resource
    Electronic Resource
    A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 2. Marked attenuation of the metabolic deterioration by somatostatin (1983)
    Springer
    Diabetologia 24 (1983), S. 319-325 
    Details
    ISSN: 1432-0428
    Keywords: Continuous subcutaneous infusion ; Type 1 diabetes ; glucagon ; growth hormone ; insulin ; non-esterified fatty acids ; pump ; somatostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the respective roles of insulin deprivation and counter-regulatory hormones in the metabolic deterioration after a nocturnal interruption of continuous subcutaneous insulin infusion in Type 1 (insulin-dependent) diabetic patients without residual insulin secretion. Changes in blood glucose, plasma non-esterified fatty acids, 3-hydroxybutyrate, glucagon, growth hormone, cortisol and free insulin in seven patients whose pumps were deliberately stopped between 23.00 h and 05.00 h were compared in two randomized tests carried out either during an intravenous somatostatin infusion at a constant rate of 250 μg/h from 22.00 h until 07.00 h (somatostatin test) or during a saline infusion (control test). Arrest of the pumps resulted in a rapid (already significant after 1 h) and progressive (nadir after 5–6 h) decrease in plasma free insulin concentrations with no statistically significant differences between the two tests. Somatostatin remarkably depressed basal levels of growth hormone and the late significant increase in glucagon (+39±14 pg/ml at 05.00 h, 2p〈 0.05) observed during the control test. In contrast, cortisol secretion was not inhibited. The sharp linear increase in blood glucose observed from 01.00 to 05.00 h (38±4 μmol·l-1· min-1) in the control test was fully suppressed with a paradoxical tendency to hypoglycaemia until 03.00 h and a less steep rise from 03.00 to 05.00 h (18±5 μmol·l-1·min-1, 2p〈0.05) during the somatostatin test. Initial plasma non-esterified fatty acids levels were slightly higher on somatostatin but did not show any statistically significant rise despite arrest of the pump, contrasting with the increase from 491±27 to 741±96 μmol/l (2p〈0.05) in the control test. Consequently, plasma non-esterified fatty acids levels from 01.00 to 05.00 h were not significantly different between the two tests. The abrupt rise in 3-hydroxybutyrate from 00.00 to 05.00 h (3.0±0.5 μmol·l-1·min-1) in the control test was not altered by somatostatin until 03.00 h. In contrast, during the last 2 h after arrest of the pump, somatostatin inhibited any further rise in 3-hydroxybutyrate levels. In conclusion, somatostatin significantly reduces metabolic deterioration during a 6-h nocturnal interruption of a continuous subcutaneous insulin infusion. Somatostatin-induced glucagon suppression seems to be involved in reducing hyperglycaemia as well as, together with the somatostatin-induced growth hormone suppression, in the limitation of hepatic ketogenesis in hours 5 and 6 after cessation of insulin supply. In contrast, the early rise in 3-hydroxybutyrateplasma levels is unaffected by somatostatin and thus appears entirely due to the fall in free insulin circulating concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00251816
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  • 2
    Electronic Resource
    Electronic Resource
    Impaired insulin-induced erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose disposal in Type 2 (non-insulin-dependent) diabetic patients (1988)
    Springer
    Diabetologia 31 (1988), S. 910-915 
    Details
    ISSN: 1432-0428
    Keywords: Erythrocyte ; Type 2 (non-insulin-dependent) diabetes ; insulin ; insulin-resistance ; magnesium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal plasma and erythrocyte magnesium levels were significantly lower in diabetic patients than in control subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both control subjects (p〈0.001) and patients with diabetes (p〈0.001). However, even in the presence of 100mU/l insulin, the erythrocyte magnesium content of patients with Type 2 diabetes was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when red cells of diabetic patients were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in Type 2 diabetic patients results essentially from a post-receptor defect. In the diabetic patients, the Δ increase in erythrocyte magnesium levels (calculated as the net increase between basal and 100 mU/l insulin-induced erythrocyte magnesium levels) was negatively correlated with plasma insulin levels (r=−0.86; p〈0.001) and with body mass index (r=−0.90; p〈0.001); it was positively correlated with the glucose disappearance constant Kg after intravenous glucose injection (r=0.79; p〈0.01), with the amount of glucose required to keep euglycaemia despite hyperinsulinaemia in a glucose clamp (r=0.88; p〈0.001), and with the metabolic clearance rate of glucose during the clamp (r=0.82; p〈0.001). These results demonstrate that insulin-induced erythrocyte magnesium accumulation is impaired in patients with Type 2 diabetes and that such defect is correlated to impaired insulin-mediated glucose disposal in these patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265376
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  • 3
    Electronic Resource
    Electronic Resource
    Alterations in the ultradian oscillations of insulin secretion and plasma glucose in aging (1996)
    Springer
    Diabetologia 39 (1996), S. 564-572 
    Details
    ISSN: 1432-0428
    Keywords: Aging ; ultradian oscillations ; insulin secretion ; glucose tolerance ; pulsatility ; beta cell ; feedback loop ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal insulin secretion includes oscillations with a period length of 80–150 min which are tightly coupled to glucose oscillations of similar period. To determine whether normal aging is associated with alterations in these ultradian oscillations, eight, modestly overweight, older men (65±5 years) and eight weight-matched young control subjects (25±4 years) were studied during 53 h of constant glucose infusion. Blood samples were collected every 20 min and insulin secretion rates were calculated by deconvolution. Ultradian oscillations of glucose and insulin secretion were evident in both groups. Pulse frequency was similar for glucose and insulin secretion, and was not affected by age. The absolute amplitude of the glucose oscillations was similar in both groups but their relative amplitude was slightly dampened in the older adults. Both the absolute and the relative amplitudes of insulin secretory oscillations were markedly reduced in the older subjects. The normal linear increase in the amplitude of insulin oscillations occurring with increasing amplitudes of glucose oscillations was still present in the older adults but analysis of covariance indicated that the slope was significantly lower than in the young control subjects (p〈0.0005), reflecting a decreased responsiveness of the beta cell to glucose changes. The temporal concordance between insulin and glucose oscillations, as estimated by pulse concomitancy and cross-correlation, was also lower in older subjects. The similarities between the alterations in the ultradian oscillations of insulin secretion and glucose in older healthy adults and those occurring in diabetic patients suggest that an impairment of beta-cell function may play a primary role in the deterioration of glucose tolerance in aging.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403303
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  • 4
    Electronic Resource
    Electronic Resource
    Blood collection while using a continuous glucose analyzer without insertion of an additional venous catheter (1983)
    Springer
    Diabetologia 25 (1983), S. 120-122 
    Details
    ISSN: 1432-0428
    Keywords: Biostator ; continuous blood collection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A new method for continuous blood collection using the Biostator is described. Blood is withdrawn through the double lumen catheter by a tube installed in the optional channel of the infusion pump. The amount of blood withdrawn from the patient is slightly greater than that necessary for continuous glucose analysis; the excess blood can be collected into assay tubes. Blood collection is continuous and produces a sample of diluted heparinized blood. The volume of blood collected depends on the size of the tube used, i.e. for a tube with a lumen diameter of 0.020 inches, the mean (±SD) volume collected was 1.21 ±0.07 ml/10 min (n = 13). The mean time interval between sampling and arrival at the glucose sensor by the double lumen catheter was 119 versus 108 s with the conventional method. The proposed modification does not affect blood glucose measurements (correlation coefficient compared with the reference method r = 0.9572; n = 13). To compensate for blood dilution, a dilution-factor depending on tubing diameter has to be calculated in each experiment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00250899
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  • 5
    Electronic Resource
    Electronic Resource
    Pulsatility of insulin and glucagon release: physiological significance and pharmacological implications (1987)
    Springer
    Diabetologia 30 (1987), S. 443-452 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279610
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  • 6
    Electronic Resource
    Electronic Resource
    Alterations in the ultradian oscillations of insulin secretion and plasma glucose in aging (1996)
    Springer
    Diabetologia 39 (1996), S. 564-572 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Aging ; ultradian oscillations ; insulin secretion ; glucose tolerance ; pulsatility ; beta cell ; feedback loop ; diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal insulin secretion includes oscillations with a period length of 80–150 min which are tightly coupled to glucose oscillations of similar period. To determine whether normal aging is associated with alterations in these ultradian oscillations, eight, modestly overweight, older men (65 ± 5 years) and eight weight-matched young control subjects (25 ± 4 years) were studied during 53 h of constant glucose infusion. Blood samples were collected every 20 min and insulin secretion rates were calculated by deconvolution. Ultradian oscillations of glucose and insulin secretion were evident in both groups. Pulse frequency was similar for glucose and insulin secretion, and was not affected by age. The absolute amplitude of the glucose oscillations was similar in both groups but their relative amplitude was slightly dampened in the older adults. Both the absolute and the relative amplitudes of insulin secretory oscillations were markedly reduced in the older subjects. The normal linear increase in the amplitude of insulin oscillations occurring with increasing amplitudes of glucose oscillations was still present in the older adults but analysis of covariance indicated that the slope was significantly lower than in the young control subjects (p 〈 0.0005), reflecting a decreased responsiveness of the beta cell to glucose changes. The temporal concordance between insulin and glucose oscillations, as estimated by pulse concomitancy and cross-correlation, was also lower in older subjects. The similarities between the alterations in the ultradian oscillations of insulin secretion and glucose in older healthy adults and those occurring in diabetic patients suggest that an impairment of beta-cell function may play a primary role in the deterioration of glucose tolerance in aging. [Diabetologia (1996) 39: 564–572]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403303
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  • 7
    Electronic Resource
    Electronic Resource
    Sandostatin, a new analogue of somatostatin, reduces the metabolic changes induced by the nocturnal interruption of continuous subcutaneous insulin infusion in Type 1 (insulin-dependent) diabetic patients (1989)
    Springer
    Diabetologia 32 (1989), S. 801-809 
    Details
    ISSN: 1432-0428
    Keywords: Insulin pump ; metabolic deterioration ; somatostatin analogue ; Type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary With the aim of assessing a new somatostatin analogue to prevent the metabolic changes induced by a 6-h nocturnal arrest of an insulin pump, nine C-peptide negative Type 1 (insulin-dependent) diabetic patients were submitted blindly to two interruptions (from 23.00 to 05.00 hours) of their continuous s.c. insulin infusion, once after a single s.c. injection at 23.00 hours of 50 μg SMS 201-995 (Sandostatin, Sandoz) and once after 0.9% NaCl. Plasma SMS 201-995 levels peaked at 24.00 hours and then declined with an elimination half-life averaging 144±15 min. Plasma glucagon and growth hormone levels were significantly reduced after SMS 201-995 whereas the progressive fall in plasma-free insulin levels from 23.00 to 05.00 hours was unaffected. In the control test, blood glucose levels tended to decrease slightly from 23.00 to 02.00 hours and then increased markedly from 02.00 to 05.00 hours (+5.3±1.5mmol/l) while after SMS 201-995 they decreased significantly from 23.00 to 02.00 hours (−2.6±0.5 mmol/l), resulting in values below 3 mmol/l in seven subjects, but showed a secondary increase until 05.00 hours (+3.5±1.5 mmol vs 23.00h; p〈0.05 vs 0.9% NaCl). While the rises in plasma non-esterified fatty acid and glycerol levels were not reduced by SMS 201-995, the increase in plasma 3-hydroxybutyrate levels, although similar from 23.00 to 02.00 hours, was significantly reduced from 02.00 to 05.00 hours (+77±20 vs+124±31 μmol·l−1·h−1 p〈0.005). Thus, SMS 201-995 significantly reduced the metabolic alterations due to a 6-h nocturnal interruption of a continuous s.c. insulin infusion but at the cost of a rather high risk of early hypoglycaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00264911
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  • 8
    Electronic Resource
    Electronic Resource
    Glipizide increases plasma insulin but not C-peptide level after a standardized breakfast in type 2 diabetic patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 471-474 
    Details
    ISSN: 1432-1041
    Keywords: glipizide ; diabetes Type 2 ; C-peptide plasma level ; insulin plasma level ; sulphonylurea ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Peripheral blood glucose, plasma insulin and C-peptide levels were investigated after giving a standardized breakfast (500 kcal, 60g carbohydrates) to 10 nonobese Type 2 diabetic patients previously treated by diet alone. Each patient received at random, at 1 week intervals, either 5 mg glipizide (meal + glipizide) or a placebo (meal alone) 30 min before breakfast. Basal values of blood glucose, plasma insulin and C-peptide were similar on both occasions. After meal + glipizide, the blood glucose increase was sharply limited whereas the rise in plasma insulin was steeper and reached twice as high a level. In contrast, the rise in plasma C-peptide was similar in both conditions. Consequently, the areas under the curves (0–300 min) showed a marked reduction in blood glucose after meal + glipizide (2289±149 versus 3101±169 mmol·min/l; 2p〈0.001), associated with a significant increase in plasma insulin (14219±3261 versus 7591±1173 µU·min/ml; 2p〈0.025) but no significant change in plasma C-peptide (342±45 versus 326±34 pmol·min/ml; N.S.). The insulin/C-peptide molar ratio was thus significantly increased after meal + glipizide (0.41±0.06 versus 0.23±0.04 at the 60th min; 2p〈0.02). The dissociation between the responses of insulin and C-peptide suggests that a single dose of 5 mg glipizide in Type 2 diabetic subjects may enhance availability of peripheral insulin by extrapancreatic mechanism(s). This phenomenon may result in a higher circulating level of the hormone and therefore represent a further mode of action of sulphonylureas. Finally, the usual concept that peripheral insulin levels reflect true insulin secretion may be misleading in studies dealing with sulphonylureas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542143
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  • 9
    Electronic Resource
    Electronic Resource
    Diuretic activity of torasemide and furosemide in chronic heart failure: A comparative double blind cross-over study (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 35-42 
    Details
    ISSN: 1432-1041
    Keywords: torasemide ; furosemide ; diuretic activity ; chronic heart failure ; electrolyte excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The diuretic effects of torasemide and of furosemide were compared in a double blind cross-over study in 13 patients with stable chronic heart failure. Single doses of 10 mg and 20 mg of torasemide and of 40 mg of furosemide were given orally, in a randomized order on 3 consecutive days. In addition, a placebo was administered on the day preceding the 3 active drug treatment days to obtain control data. Each experimental day was divided into three urine collection periods — 0 to 4 h, 4 to 12 h and 12 to 24 h. Urine output, ion excretion and clearance were measured during each of the 3 periods as well as for the 24-h period. Torasemide 20 mg was distinctly more active in each of the 3 collection periods and in the 24-h period than furosemide 40 mg, whereas no significant difference was found between furosemide 40 mg and torasemide 10 mg for most of the experimental data. From 0 to 4 h, both torasemide and furosemide significantly increased the urinary flow rate and the urinary excretion of sodium, chloride and calcium, while they decreased the urinary osmolality when compared to placebo. All the effects persisted in the 4 to 12 h period after torasemide 20 mg in contrast to furosemide, whose effects were limited to the 0 to 4 h period. In the third period (12–24 h), the urine volume fell below the placebo value after furosemide but not torasemide, and only torasemide 20 mg was followed by a persistent decrease in the urine osmolality. Both diuretics increased the free water clearance, but this phenomenon was slightly greater after torasemide. Finally, urinary potassium excretion was increased by both doses of torasemide and furosemide, with no significant difference between the three experiments. Torasemide and furosemide were well tolerated; no clinical or biochemical adverse effects occurred after administration of either of the compounds. Torasemide is a new loop diuretic which may constitute a good alternative to furosemide in the treatment of oedema in chronic heart failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541465
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  • 10
    Electronic Resource
    Electronic Resource
    Availability of glucose ingested during muscle exercise performed under acipimox-induced lipolysis blockade (1994)
    Springer
    European journal of applied physiology 68 (1994), S. 406-412 
    Details
    ISSN: 1439-6327
    Keywords: Acipimox ; Exercise ; Metabolism ; Oral glucose ; Stable isotopes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated the percentage of carbohydrate utilization than can be accounted for by glucose ingested during exercise performed after the ingestion of the potent lipolysis inhibitor Acipimox. Six healthy male volunteers exercised for 3 h on a treadmill at about 45% of their maximal oxygen uptake, 75 min after having ingested 250 mg of Acipimox. After 15-min adaptation to exercise, they ingested either glucose dissolved in water, 50 g at time 0 min and 25 g at time 60 and 120 min (glucose, G) or sweetened water (control, C). Naturally labelled [13C]glucose was used to follow the conversion of the ingested glucose to expired-air CO2. Acipimox inhibited lipolysis in a similar manner in both experimental conditions. This was reflected by an almost complete suppression of the exercise-induced increase in plasma free fatty acid and glycerol and by an almost constant rate of lipid oxidation. Total carbohydrate oxidation evaluated by indirect calorimetry, was similar in both experimental conditions [C, 182, (SEM 21); G, 194 (SEM 16) g · 3 h−1], as was lipid oxidation [C, 57 (SEM 6); G, 61 (SEM 3) g · 3 h−1]. Exogenous glucose oxidation during exercise G, calculated by the changes in13C:12C ratio of expired air CO2, averaged 66 (SEM 5) g · 3 h−1 (19% of the total energy requirement). Consequently, endogenous carbohydrate utilization was significantly smaller after glucose than after placebo ingestion: 128 (SEM 18) versus 182 (SEM 21) g · 3 h−1, respectively (P 〈 0.05). Symptoms of intense fatigue and leg cramps observed with intake of sweet placebo were absent with glucose ingestion. In conclusion, we found glucose ingestion during 3-h exercise with lipolysis blockade could provide metabolic substrate permitting a significant sparing of endogenous carbohydrate and consequently an improvement in performance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00843737
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