Insulin oscillations per se do not affect glucose turnover parameters in normal man.
; Scheen, André ; Verdin, Emeline et al
in Journal of Clinical Endocrinology and Metabolism (1986), 63(2), 520-5
To compare the metabolic effects of pulsatile vs. continuous iv insulin infusion, normal men had two glucose-controlled iv glucose infusions using the Biostator for 260 min, during which endogenous ... [more ▼]
To compare the metabolic effects of pulsatile vs. continuous iv insulin infusion, normal men had two glucose-controlled iv glucose infusions using the Biostator for 260 min, during which endogenous pancreatic hormone secretion was inhibited by a somatostatin infusion and glucagon was replaced by continuous glucagon infusion. The two tests were performed at 1-week intervals, during which human insulin was infused either continuously at a constant rate of 0.2 mU kg-1 min-1 or in a pulsatile manner at a rate of 1.3 mU kg-1 min-1 with a switching on/off length of 2/11 min. Blood glucose levels and glucose infusion rates (GIR) were continuously monitored, and glucose turnover was estimated using a [3H]glucose infusion. In both tests, plasma C-peptide dropped markedly, whereas plasma glucagon levels were about twice basal values. Plasma insulin averaged 7 mU liter-1 during continuous infusion and oscillated between 1.5 and 35 mU liter-1 during pulsatile delivery. During the first 30-60 min of both tests, the glucose appearance rate and endogenous glucose production (EGP) increased, resulting in moderate hyperglycemia, which completely suppressed GIR. During the last 65 min, EGP declined, while the glucose disappearance rate and the glucose MCR increased, so that GIR increased progressively to maintain the blood glucose clamped at about 5 mmol liter-1. During this period, no significant differences were found between the two modes of insulin administration for any of the parameters studied. Thus, continuous and pulsatile insulin iv infusion, resulting in physiological peripheral plasma insulin levels, altered the glucose turnover parameters equally, in particular inhibiting EGP, which was stimulated by glucagon during the first part of the study, and stimulating peripheral glucose uptake at the end of the study period. [less ▲]Detailed reference viewed: 19 (6 ULg)
Insulin induces opposite changes in plasma and erythrocyte magnesium concentrations in normal man.
; ; et al
in Diabetologia (1986), 29(9), 644-7
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 ... [more ▼]
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 less than 0.01 and p less than 0.05 respectively) and a significant increase in erythrocyte magnesium levels (p less than 0.01 and p less than 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/l) was maintained despite hyperinsulinaemia (110-130 mU/l). During in vitro incubations, glucose (5 mmol/l) did not modify erythrocyte magnesium levels. In contrast, erythrocyte magnesium levels were significantly increased (p less than 0.01) by insulin (100 mU/l), an effect entirely abolished by ouabain (5 X 10(-4) mol/l). 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. [less ▲]Detailed reference viewed: 10 (0 ULg)
Immunogenicity of semisynthetic human insulin in man. Long-term comparison with porcine monocomponent insulin.
; ; et al
in Acta Diabetologica Latina (1986), 23(2), 101-6
The levels of circulating IgG-insulin antibodies were determined in two groups of diabetic patients before and at 3-month intervals after starting insulin treatment either with monocomponent porcine ... [more ▼]
The levels of circulating IgG-insulin antibodies were determined in two groups of diabetic patients before and at 3-month intervals after starting insulin treatment either with monocomponent porcine insulin (n = 17) or with human semisynthetic insulin (SH) (n = 16). Patients were followed during 15.1 +/- 1.0 and 19.9 +/- 1.1 months, respectively (m +/- SEM). In addition, the quality of metabolic control and residual B-cell function were evaluated in the group under treatment with SHI. The percentage of patients who remained antibody-free after 12-21 months of treatment was 67.75% in the human insulin-treated group and only 25-43% in the one receiving porcine insulin (p less than 0.01). Moreover, insulin antibody titers, when present, were usually lower in subjects treated with human insulin. In SHI-treated patients: metabolic control was excellent during the first months of treatment as evidenced by values of mean daily blood glucose (7.3 +/- 0.6 mmol/l), M-index according to Schlichtkrull (7.4 +/- 2.4) and Hb1c (6.8 +/- 0.6%); residual B-cell function, evaluated at 3-month intervals by a circadian profile of plasma C-peptide did not decrease throughout the study; and a significant deterioration of blood glucose control occurred after 18 months of treatment, which might have been due to a less intensive supervision of the patients by the physicians and/or less careful attention by the patients themselves. This observation confirms the need for a continuous education of the patients regardless of the type of insulin used. [less ▲]Detailed reference viewed: 17 (0 ULg)
Insulin-stimulated glucose disposal is not increased in anorexia nervosa.
; Scheen, André ; Lefebvre, Pierre et al
in Journal of Clinical Endocrinology and Metabolism (1985), 60(2), 311-4
Insulin-stimulated glucose disposal was investigated using the euglycemic hyperinsulinemic glucose clamp technique in six women with anorexia nervosa (27.3 +/- 4.9 yr old; weight, 38.8 +/- 6.6 kg) and ... [more ▼]
Insulin-stimulated glucose disposal was investigated using the euglycemic hyperinsulinemic glucose clamp technique in six women with anorexia nervosa (27.3 +/- 4.9 yr old; weight, 38.8 +/- 6.6 kg) and compared to results obtained in six normal women (22.6 +/- 1.2 yr old; weight, 58 +/- 2.5 kg) and seven obese women (26.8 +/- 7.7 yr old; weight, 92.5 +/- 13.8 kg). The glucose clamp was performed for 2 h using the Biostator and a continuous insulin infusion of 100 mU kg-1 h-1. Plasma levels of insulin were determined at 30-min intervals. Plasma levels of glucagon, FFA, glycerol, 3-hydroxy-butyrate, and alanine were measured basally. Blood glucose levels were similar in normal subjects and anorectic patients; they were slightly but significantly higher in the obese patients. The indices of insulin sensitivity measured were the MCR of glucose and the ratio of glucose infused to insulin infused (G/I). They were very similar in anorectic subjects [MCR, 13.5 +/- 2.4 (+/- SEM) ml kg-1 min-1; G/I, 5.2 +/- 0.9 mg/mU) and normal subjects (MCR, 13.5 +/- 1.7 ml kg-1 min-1; G/I, 5.2 +/- 0.4 mg/mU), but were significantly reduced in obese patients (MCR, 5.1 +/- 0.8 ml kg-1 min-1; G/I, 2.6 +/- 0.3 mg/mU; P less than 0.0025). Differences in plasma insulin among the three groups were not statistically significant. Plasma alanine levels were higher in anorectic than in normal or obese subjects, suggesting defective gluconeogenesis. Thus, insulin-stimulated glucose disposal is normal in patients with anorexia nervosa, a finding that contrasts with the previously reported increase in erythrocyte insulin receptors in this disease. [less ▲]Detailed reference viewed: 16 (0 ULg)
Glipizide increases plasma insulin but not C-peptide level after a standardized breakfast in type 2 diabetic patients.
Scheen, André ; Lefebvre, Pierre ;
in European Journal of Clinical Pharmacology (1984), 26(4), 471-4
Peripheral blood glucose, plasma insulin and C-peptide levels were investigated after giving a standardized breakfast (500 kcal, 60 g carbohydrates) to 10 nonobese Type 2 diabetic patients previously ... [more ▼]
Peripheral blood glucose, plasma insulin and C-peptide levels were investigated after giving a standardized breakfast (500 kcal, 60 g 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 X min/1; 2p less than 0.001), associated with a significant increase in plasma insulin (14219 +/- 3261 versus 7591 +/- 1173 microU X min/ml; 2p less than 0.025) but no significant change in plasma C-peptide (342 +/- 45 versus 326 +/- 34 pmol X 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 28 (0 ULg)
Metabolic alterations after a two-hour nocturnal interruption of a continuous subcutaneous insulin infusion.
Scheen, André ; ; Jandrain, Bernard et al
in Diabetes Care (1984), 7(4), 338-42
In order to evaluate the metabolic consequences of a 2-h nocturnal interruption of continuous subcutaneous insulin infusion (CSII), seven insulin-dependent diabetic patients without residual insulin ... [more ▼]
In order to evaluate the metabolic consequences of a 2-h nocturnal interruption of continuous subcutaneous insulin infusion (CSII), seven insulin-dependent diabetic patients without residual insulin secretion were investigated. The changes in blood glucose, plasma free insulin, glucagon, free fatty acids, and 3-hydroxybutyrate (3 OH-B) concentrations have been compared during two randomized tests carried out either during the normal functioning of a Mill-Hill pump from 10 p.m. to 8 a.m. (1.00 +/- 0.06 U insulin/h, keeping adequate metabolic control) or during the same conditions but with a deliberate arrest of the pump between 11 p.m. and 1 a.m. Considering the value recorded at 11 p.m. as reference, interruption of the insulin infusion resulted in: (1) a rapid (already significant after 1 h) and sustained (maximal fall: --12.5 +/- 2.5 mU/L at 3 a.m.) decrease in plasma free insulin; (2) a delayed (significant after 4 h) and linear rise in blood glucose (maximal increase: + 4.0 +/- 1.3 mmol/L at 5 a.m.); (3) an early (significant at midnight) and prolonged rise in plasma free fatty acids (+ 387 +/- 148 mumol/L at 3 a.m.); (4) a delayed (significant after 3 h) and sustained increase in plasma 3 OH-B (+ 347 +/- 88 mumol/L at 3 a.m.); and (5) no significant changes in plasma glucagon. Thus, a 2-h interruption of CSII in resting nocturnal conditions is sufficient to induce significant, delayed, and sustained metabolic alterations in C-peptide-negative patients despite good baseline blood glucose control. Resetting the pump at its basal rate is insufficient to quickly restore adequate circulating insulin levels and effectively counteract the metabolic disturbances. The efficacy of a bolus insulin injection in these conditions should be evaluated. [less ▲]Detailed reference viewed: 7 (0 ULg)
A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 1. Metabolic and hormonal consequences and scheme for a prompt return to adequate control.
; Scheen, André ; et al
in Diabetologia (1983), 24(5), 314-8
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 ... [more ▼]
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 nonesterified fatty acids which remained in the range of 700-800 mumol/l; (4) an early and linear rise in plasma 3-hydroxybutyrate, significant after 1 h and averaging 1290 +/- 140 mumol/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 05.00 h 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. [less ▲]Detailed reference viewed: 26 (0 ULg)
Blood collection while using a continuous glucose analyzer without insertion of an additional venous catheter.
; Scheen, André ; et al
in Diabetologia (1983), 25(2), 120-2
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 ... [more ▼]
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. [less ▲]Detailed reference viewed: 19 (0 ULg)
Metabolic adaptation to prolonged exercise in severely obese subjects.
Scheen, André ; Pirnay, Freddy ; et al
in International Journal of Obesity & Related Metabolic Disorders (1983), 7(3), 221-9
In investigating the metabolic adaptation to prolonged exercise in markedly obese subjects, we compared blood glucose, plasma lactate, free fatty acids, insulin and glucagon concentrations during 3 h of ... [more ▼]
In investigating the metabolic adaptation to prolonged exercise in markedly obese subjects, we compared blood glucose, plasma lactate, free fatty acids, insulin and glucagon concentrations during 3 h of treadmill exercise in nine severely obese male patients (OB) (weight excess 84 +/- 7 per cent of their ideal body weight) and in nine healthy controls (C). Speed and slope of treadmill were selected to give a similar oxygen consumption in both groups (OB: 1.61 +/- 0.08 1/min; C: 1.72 +/- 0.07 1/min). Under these conditions, heart rate was similar in both groups, whereas ventilation was significantly lower in overweight subjects. In obese patients, plasma free fatty acid (FFA) levels were higher in the basal state (OB: 740 +/- 43 mumol/l; C: 602 +/- 40 mumol/l, 2 P less than 0.05) but showed a lower increase during the exercise period (OB: + 576 +/- 135 mumol/l; C: + 1071 +/- 100 mumol/l, 2 P less than 0.02). This impaired FFA mobilization was related to significantly higher insulin (IRI) levels throughout the exercise period as shown by the regression line of exercise-induced FFA increase (y, mumol/l) vs mean plasma IRI during exercise (x, microU/ml): y = 1238 - 60 x, r = -0.709, 2 P less than 0.001. Lack of glucagon increase could also contribute to the lower rise of FFA in obese subjects. A correspondingly increased contribution of carbohydrates to the energy supply is suggested by a significant decline in blood glucose and higher lactate plasma concentrations during the second half of the exercise period in overweight patients. These abnormalities could represent a metabolic limitation for performing prolonged exercise in markedly obese patients. [less ▲]Detailed reference viewed: 26 (1 ULg)
Effect of protein-supplemented fasting on the fuel-hormone response to prolonged exercise in obese subjects.
Scheen, André ; ; et al
in International Journal of Obesity & Related Metabolic Disorders (1983), 7(4), 327-37
This study aimed at investigating the influence of protein-supplemented fasting (PSF) on the tolerance and the fuel-hormone response to endurance exercise in the severely obese subject. For this purpose ... [more ▼]
This study aimed at investigating the influence of protein-supplemented fasting (PSF) on the tolerance and the fuel-hormone response to endurance exercise in the severely obese subject. For this purpose, eight obese men (27 +/- 2 yr, 182 +/- 7 per cent of ideal body weight) exercised on a horizontal treadmill (4 km/h) during 3 h before and after 13 d of PSF (Alburone, 70 g protein/day). Because of the 8.9 +/- 0.7 kg weight loss and the corresponding lower energy cost, exercise oxygen consumption decreased from 1.6 +/- 0.1 (before PSF) to 1.4 +/- 0.1 l/min (after PSF). In contrast, mean exercise heart rate was identical (119 +/- 5/min) in both conditions, resulting in a lower oxygen pulse after PSF. The mean respiratory quotient measured during exercise was lower after PSF (0.72 +/- 0.01 vs 0.75 +/- 0.01 2 P less than 0.05), thus demonstrating a higher fat utilization. This was supported by a higher exercise-induced plasma free fatty acid (FFA) mobilization after PSF (delta plasma FFA: + 675 +/- 101 vs + 376 +/- 121 mumol/l, 2 P less than 0.05). This metabolic adaptation mainly results from two mechanisms: a significantly lower plasma IRI at rest and during exercise after PSF (5.7 +/- 0.8 vs 11.4 +/- 1.4 microunits/ml, 2 P less than 0.001); and a lower basal blood glucose (4.2 +/- 0.2 vs 4.6 +/- 0.1 mmol/l) and an earlier decrease of glucose (30th vs 90th min) during exercise after PSF, suggesting a relative depletion of the carbohydrates stores. The lipolytic hormones (glucagon, epinephrine, norepinephrine, cortisol, growth hormone) did not significantly increase during exercise after PSF when compared to exercise before PSF; thus, their role in the enhanced FFA mobilization appears less important. Only two of our eight subjects were unable to achieve the third hour of exercise after PSF; however, no major clinical events or electrocardiographical disturbances were observed in any of the eight subjects. In conclusion, moderate exercise can be tolerated at least for 2 h during PSF when appropriate fluid, mineral and vitamin therapy is given. Under these conditions it induces a preferential utilization of fat-derived substrates and selectively augments fat mobilization which favors weight loss. For these reasons, moderate exercise can be recommended under strict medical supervision as part of all weight reduction therapy. [less ▲]Detailed reference viewed: 15 (1 ULg)
Fate of exogneous glucose metabolism during exercise of different intensities in humans
Pirnay, Freddy ; ; Crielaard, Jean-Michel et al
in Journal of Applied Physiology (1982), 53Detailed reference viewed: 11 (1 ULg)
Hormonal and metabolic adaptation to protein-supplemented fasting in obese subjects.
Scheen, André ; ; Scheen, Myriam et al
in International Journal of Obesity & Related Metabolic Disorders (1982), 6(2), 165-74
Thirty hospitalized, severely obese patients (40 +/- 2 yr, 82 +/- 4 percent weight excess) were submitted to a 13-d protein-supplemented fast (PSF) with 70 g milk proteins/d (1.26 MJ or 300 kcal). The ... [more ▼]
Thirty hospitalized, severely obese patients (40 +/- 2 yr, 82 +/- 4 percent weight excess) were submitted to a 13-d protein-supplemented fast (PSF) with 70 g milk proteins/d (1.26 MJ or 300 kcal). The mean weight loss during PSF was 5.4 +/- 0.3 kg corresponding to 422 +/- 39 g/d. Comparison of the urinary nitrogen excretion with daily protein intake revealed that the nitrogen balance was equilibrated during PSF. Blood glucose decreased moderately but significantly during the whole PSF period whereas plasma insulin was only reduced during the first 9 d and tended to rise thereafter. Plasma FFA increased rapidly and remained elevated until the end of the study (+ 60 per cent); serum total cholesterol and plasma triglycerides showed a 26 and a 35 per cent decrease respectively. Basal plasma glucagon was slightly increased. Due to the low sodium intake (42 mmol/d) urinary sodium excretion dropped rapidly. Simultaneously both systolic (-13 mmHg) and diastolic (-7 mmHg) arterial blood pressure decreased significantly. The biological tolerance was good: metabolic acidosis was prevented with sodium bicarbonate, excessive rise in serum uric acid was corrected with allopurinol and a marked decrease in serum potassium was avoided with an appropriate dose of spironolactone. Twenty-six patients could be weighed 6 to 15 months after PSF: 12 showed a further weight reduction (6.6 +/- 1.6 kg) and seven a discrete weight gain (1.0 +/- 0.4 kg). Thus, PSF was well accepted and was profitable in 19 out of our 30 patients. It should be restricted to cases of severe and refractory obesity and performed under careful medical supervision. [less ▲]Detailed reference viewed: 13 (1 ULg)
Effect of indomethacin on the metabolic and hormonal response to a standardized breakfast in normal subjects.
; ; Scheen, André et al
in Acta Diabetologica Latina (1981), 18(3), 259-66
We have investigated the influence of a single oral administration of indomethacin on blood glucose, plasma free fatty acids (FFA), alpha-amino-nitrogen, insulin and glucagon concentrations in young ... [more ▼]
We have investigated the influence of a single oral administration of indomethacin on blood glucose, plasma free fatty acids (FFA), alpha-amino-nitrogen, insulin and glucagon concentrations in young healthy subjects. Two groups of 6 subjects were studied, the first received a standardized 500 kcal mixed meal without any previous drug administration (controls) whereas the second group received 50 mg indomethacin 2 h before ingesting an identical meal. Plasma indomethacin concentration reached its maximum (2.36 +/- 0.36 micro g/ml) 15 min after administration and declined to 0.45 +/- 0.04 micro g/ml after 2 h. Indomethacin ingestion was followed by a significant increase in blood glucose and plasma FFA reaching their maximum value at 45 min and returning to basal levels at 120 min. No simultaneous changes in plasma alpha-amino-nitrogen, insulin or glucagon levels were detected during this period. The meal was followed by a rise in blood glucose and plasma insulin as well as by a decrease in plasma FFA concentration. No significant differences were detected between the controls and the subjects receiving indomethacin. In controls, the meal was followed by a rise in plasma alpha-amino-nitrogen and a modest although significant increase in glucagon levels. In indomethacin-treated subjects, the increment of alpha-amino-nitrogen was less marked and the increase in plasma glucagon was not observed. Thus, indomethacin by itself can exert several metabolic effects; however, it does not deteriorate the blood glucose or insulin profile after a regular meal. The present work is the first to demonstrate that an inhibitor of prostaglandin synthesis inhibits the plasma glucagon rise occurring after a physiological stimulus such as a normal meal. On the basis of previous in vitro experiments, we suggest that this effect results from an inhibition of glucagon secretion by the PG synthesis inhibitor. [less ▲]Detailed reference viewed: 29 (0 ULg)
Oxidation and orally administrated 'naturally labeled 13C-glucose' during prolonged muscular exercise : 100g versus 4 x 250g
Pirnay, Freddy ; ; Crielaard, Jean-Michel et al
in Poortmans, J. (Ed.) Biochemistry of exercise IV-A : 4th International Symposium of Biochemistry on Exercise, June 19-22, 1979, Bruxelles (1981)Detailed reference viewed: 16 (1 ULg)