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  • 1
    ISSN: 1432-0428
    Keywords: Continuous subcutaneous infusion ; Type 1 diabetes ; glucagon ; insulin ; management ; non-esterified fatty acids ; pump
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Interruption of a continuous subcutaneous insulin infusion, most often due to technical problems occurring during the night, is a not uncommon event whose metabolic consequences have received relatively little attention until now. We have therefore investigated the changes in blood glucose, plasma non-esterified fatty acids, 3-hydroxybutyrate, glucagon and free insulin in eight C-peptide negative Type 1 diabetic patients whose pumps were deliberately stopped between 23.00 h and 05.00 h. A control test with the pump functioning normally was carried out in each patient and the studies were randomized. Considering the values at 23.00 h as reference, interruption of the insulin infusion resulted in (1) a rapid decrease in plasma free insulin significant after 1 h and reaching a nadir of 6±2 mU/l after 6 h; (2) a rise in blood glucose which was significant at hour 3 and reached 17.4±1.9 mmol/l at hour 6; (3) a moderate increase in plasma non-esterified fatty acids which remained in the range of 700–800 μmol/l; (4) an early and linear rise in plasma 3-hydroxybutyrate, significant after 1 h and averaging 1290±140 μmol/l after 6 h; (5) a late increase (hour 5) in plasma glucagon. The second aim of our study was to provide for the patient a precise scheme of insulin supplements administered via the pump and based on blood glucose monitoring (Dextrostix — Glucometer) and semi-quantitative evaluation of ketonuria (Acetest). Resetting the pump at its basal rate at 05.00h and giving insulin supplements (2–8 U) at 06.45 h (with the usual breakfast dose) and again at 10.00 h have proved efficacious in restoring satisfactory metabolic control by noon the day after starting the experiment. These results form practical recommendations to patients undergoing this type of accident.
    Type of Medium: Electronic Resource
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  • 2
    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
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  • 3
    ISSN: 1432-0428
    Keywords: Glucose clamp ; insulin ; magnesium ; oral glucose tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrophotometry in 10 healthy volunteers during an oral glucose tolerance test and during an euglycaemic hyperinsulinaemic glucose clamp. At min 180 and 210 of the oral glucose tolerance test, a significant decline in plasma magnesium levels (p 〈 0.01 andp 〈 0.05 respectively) and a significant increase in erythrocyte magnesium levels (p 〈 0.01 andp 〈 0.05 respectively) were observed. Similar changes were seen during the second hour of the glucose clamp, during which euglycaemia (4.1 ± 0.4 mmol/1) was maintained despite hyperinsulinaemia (110–130 mU/1). During in vitro incubations, glucose (5 mmol/1) did not modify erythrocyte magnesium levels. In contrast, erythrocyte magnesium levels were significantly increased (p 〈 0.01) by insulin (100 mU/1), an effect entirely abolished by ouabain (5 .10−4 mol/1). These results suggest that insulin induces a shift of magnesium from the plasma to the erythrocytes both in vivo and in vitro. These data may help to interprete the abnormalities in magnesium circulating levels frequently reported in diabetic patients.
    Type of Medium: Electronic Resource
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  • 4
    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
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 33 (1990), S. 511-514 
    ISSN: 1432-0428
    Keywords: Magnesium ; insulin ; glucose homeostasis ; diabetic complications ; dietary magnesium supplements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Magnesium is an important ion in all living cells being a cofactor of many enzymes, especially those utilising high energy phosphate bounds. The relationship between insulin and magnesium has been recently studied. In particular it has been shown that magnesium plays the role of a second messenger for insulin action; on the other hand, insulin itself has been demonstrated to be an important regulatory factor of intracellular magnesium accumulation. Conditions associated with insulin resistance, such as hypertension or aging, are also associated with low intracellular magnesium contents. In diabetes mellitus, it is suggested that low intracellular magnesium levels result from both increased urinary losses and insulin resistance. The extent to which such a low intracellular magnesium content contributes to the development of macro- and microangiopathy remains to be established. A reduced intracellular magnesium content might contribute to the impaired insulin response and action which occurs in Type 2 (non-insulin-dependent) diabetes mellitus. Chronic magnesium supplementation can contribute to an improvement in both islet Beta-cell response and insulin action in non-insulin-dependent diabetic subjects.
    Type of Medium: Electronic Resource
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  • 6
    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
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Glycogenolysis ; carbohydrate oxidation ; glucagon ; gluconeogenesis ; fructose.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C fructose (0.3 g · kg fat free mass−1· h−1) for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM (17.7 ± 1.9 μmol · kg fat free mass−1· min−1 basal vs 15.9 ± 0.9 after fructose), in obese non-diabetic subjects (12.1 ± 0.5 basal vs 13.1 ± 0.5 after fructose) and in lean healthy subjects (13.3 ± 0.5 basal vs 13.8 ± 0.6 after fructose) although 13C glucose synthesis contributed 73.2 % of EGP in lean subjects, 62.6 % in obese non-diabetic subjects, and 52.8 % in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose ingestion + hyperglucagonaemia (232 ± 9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8 % with ingestion of fructose + glucagon (p 〈 0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i. e. glycogenolysis + gluconeogenesis from non-fructose precursors). [Diabetologia (1996) 39: 580–586]
    Type of Medium: Electronic Resource
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  • 8
    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
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  • 9
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Glycogenolysis ; carbohydrate oxidation ; glucagon ; gluconeogenesis ; fructose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C fructose (0.3 g · kg fat free mass−1 · h−1) for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM (17.7±1.9 Μmol · kg fat free mass−1 · min−1 basal vs 15.9±0.9 after fructose), in obese non-diabetic subjects (12.1±0.5 basal vs 13.1±0.5 after fructose) and in lean healthy subjects (13.3±0.5 basal vs 13.8±0.6 after fructose) although 13C glucose synthesis contributed 73.2% of EGP in lean subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose ingestion + hyperglucagonaemia (232±9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8% with ingestion of fructose + glucagon (p〈0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i. e. glycogenolysis + gluconeogenesis from non-fructose precursors).
    Type of Medium: Electronic Resource
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