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Biomedical subjects

P J Lefebvre

Publications and source records attributed to P J Lefebvre.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effects of ethinyl estradiol combined with desogestrel and cyproterone acetate on glucose tolerance and insulin response to an oral glucose load: a one-year randomized, prospective, comparative trial.

To investigate the effects of two slightly estrogen-dominant, monophasic, low-dose oral contraceptives on carbohydrate metabolism, 40 healthy young women were randomly allocated to receive either 30 micrograms of ethinyl estradiol + 150 micrograms of desogestrel, a 19-nortestosterone-derived progestin (Marvelon; n = 21) or 35 micrograms of ethinyl estradiol + 2 mg of cyproterone acetate, a 17-acetoxyprogesterone derivative (Diane-35; n = (19) for a prospective observation period of 1 year. At baseline, 6, and 12 months, blood glucose, plasma insulin, and plasma C-peptide levels were measured during an oral glucose tolerance test. Although the changes were absent (Marvelon) or minimal (Diane-35) at 6 months, both groups had a slight increase in blood glucose levels at 12 months; overall glucose tolerance remaining, however, within the normal range. Plasma insulin levels remained unchanged in the Diane-35-group, which suggested increased insulin resistance, but were significantly decreased in the Marvelon group despite significant rises in plasma C-peptide levels. Comparison of plasma C-peptide and insulin changes suggests enhanced pancreatic insulin secretion and increased hepatic insulin metabolism with both Marvelon and Diane-35.

Adult↗
PubMed1989

Effects of pulsatile delivery of insulin and glucagon in humans.

The purpose of the present study was to investigate the respective effects of continuous intravenous delivery of both insulin and glucagon compared with those of pulsatile insulin (and continuous glucagon), pulsatile glucagon (and continuous insulin) and both hormones administered in a pulsatile manner (but out of phase) on various parameters of glucose turnover. The study was performed on six healthy male volunteers submitted to a 325-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin (2 micrograms/min). Four combinations of continuous and pulsatile infusions of insulin and glucagon were performed on different days and in random order. The amounts of hormone infused were identical in all instances and were 0.2 mU.kg-1.min-1 (continuous insulin), 67 ng/min (continuous glucagon), 1.3 mU.kg-1.min-1 and 435 ng/min with a switching on-off length of 2-11 min (for intermittent insulin and glucagon delivery, respectively). In the case of pulsatile administration of both hormones, the pulses of insulin and glucagon were given out of phase with a 6-min interval. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classic methodology using a D-[3-3H]glucose infusion allowed to study glucose turnover. When compared with pulsatile insulin and continuous glucagon, pulsatile glucagon and continuous insulin were characterized by a significantly higher endogenous (hepatic) glucose production. When both insulin and glucagon were delivered in a pulsatile manner, the effect of pulsatile glucagon was predominant, maintaining a high endogenous glucose production. Under no circumstance was an effect on glucose utilization or clearance detected. This study demonstrates that pulsatile delivery of insulin or glucagon in humans has greater effects in modulating endogenous glucose production than continuous infusion. Furthermore, when both insulin and glucagon are delivered intermittently and out of phase, the stimulatory effect of glucagon on endogenous glucose production prevails over the inhibitory effect of insulin.

Adult↗
PubMed1989

Effect of osmolality on availability of glucose ingested during prolonged exercise in humans.

The aim of this study was to investigate whether the osmolality of a glucose solution, ingested at the beginning of a prolonged exercise bout, affects exogenous glucose disposal. We investigated the hormonal and metabolic response to a 50-g glucose load dissolved in either 200 (protocol A), 400 (protocol B), or 600 (protocol C) ml of water and given orally 15 min after adaptation to exercise in five healthy male volunteers. Naturally labeled [13C]glucose was used to follow the conversion of the ingested glucose to expired-air CO2. Total carbohydrate oxidation (indirect calorimetry) was similar in the three protocols (A, 237 +/- 20; B, 258 +/- 17; C, 276 +/- 20 g/4 h), as was lipid oxidation (A, 128 +/- 4; B, 132 +/- 15; C, 124 +/- 12 g/4 h). Exogenous glucose oxidation rates were similar under the three experimental conditions, and the total amount of exogenous glucose utilized was slightly, but not significantly, increased with the more diluted solution (A, 42.6 +/- 4.4; B, 43.4 +/- 4.1; C, 48.7 +/- 7.2 g/4 h). The blood glucose response was similar in the three protocols. Thus, within the range investigated, the osmolality of the glucose solution ingested had no significant influence either on its oxidation (which was 86-98% of the load ingested) or on the utilization of endogenous carbohydrate, lipid, or protein stores.

Administration, Oral↗
PubMed1989

[Role of insulin and counter-regulatory hormones in the metabolic changes caused by insulin deprivation in diabetic patients].

In eight insulin dependent diabetic patients treated by continuous subcutaneous insulin infusion (1.1 +/- 0.2 U/h), the levels (measured hourly from 23 h to 05 h) of blood glucose, non esterified fatty acids (NEFA), glycerol and 3-OH-butyrate (3-OH-B) have been correlated to the circulating levels of free insulin (FIRI), glucagon, growth hormone or cortisol, in two experimental conditions: A. Insulin being infused as usual (physiological FIRI levels) and B. Progressively declining FIRI levels (insulin infusion arrested at 23 h). In condition A, blood glucose levels correlated significantly to both insulin and glucagon; NEFA, glycerol and 3OH-B correlated only to insulin. In condition B, blood glucose was significantly correlated to insulin but not to glucagon while NEFA, glycerol and 3-OH-B were significantly correlated to both hormones but not to growth hormone or cortisol. Therefore, on the metabolic deterioration that follows insulin withdrawal, growth hormone and cortisol seem to play a minor role, the main role being played by the decrease in circulating insulin levels and to a lesser extent by the increase in glucagon levels.

Adult↗
PubMed1988

Cardiovascular risk factors in a sample of a rural Belgian population: the Bellux MONICA Study.

A sample of 1949 subjects of the population of the Belgian province of Luxembourg was screened for levels of cardiovascular risk factors. Cigarette smoking was more prevalent among males (51%) than among females (17%). The relationship between smoking and socio-economic status was inverse in males (M) and direct in females (F). Blood pressure (BP) measurements showed definite high BP in 10% of this sample, and 60% of those with definite high BP were not taking any hypertensive drugs. The average total cholesterol value was 6.49 mmol/L in M and 6.45 mmol/L in F. F had lower values than M at a younger age, but higher values than M at an older age. The high-density lipoprotein cholesterol was higher in F (1.57 mmol/L) than in M (1.27 mmol/L). Diabetes was present in 4.2% of this sample. In nearly half of these participants, the disease had been discovered during the screening. Obesity was especially frequently among F in all three age groups. In conclusion, the main cardiovascular risk factors were found to be at a fairly high level in this population sample.

Adult↗
PubMed1988

Altered metabolic and hormonal responses to epinephrine and beta-endorphin in human obesity.

Catecholamines and endogenous opioid peptides are released in response to stress. Exogenous infusions of epinephrine and beta-endorphin (both in doses of 15, 50, and 80 ng/kg.min sequentially, each dose lasting 30 min) were used to mimic short term stress in both normal weight (body mass index, less than 25 kg/m2) and obese (body mass index, greater than 30 kg/m2) subjects. Fasting plasma insulin, C-peptide, and beta-endorphin concentrations were significantly higher in the obese than in the normal subjects (P less than 0.01-0.005). In lean subjects epinephrine produced significant increases in plasma glucose levels, but no appreciable changes in plasma insulin, C-peptide, or glucagon. Infusion of beta-endorphin in the same subjects caused plasma glucose and glucagon to rise, but insulin and C-peptide levels did not change. The simultaneous infusion of epinephrine and beta-endorphin produced a glycemic response which, although greater, was not significantly different than the sum of the responses to the individual hormone infusions. However, the two hormones had a synergistic interaction on plasma glucagon levels [total glucagon response, 2275 +/- 370 pg/min.mL (ng/min.L); sum of single effects, 750 +/- 152 (+/- SE) pg/min.mL (ng/min.L); P less than 0.01]. The plasma epinephrine [207 +/- 21, 607 +/- 70, and 1205 +/- 134 pg/mL (1130 +/- 115, 3640 +/- 382, and 6577 +/- 691 pmol/L] and beta-endorphin [875 +/- 88, 1250 +/- 137, and 1562 +/- 165 pg/mL (250 +/- 25, 358 +/- 39, and 447 +/- 47 pmol/L] concentrations attained during the infusions of each single hormone were not different from those recorded during the combined hormonal infusion. In obese subjects epinephrine raised plasma glucose levels and caused dose-related increments of plasma glucagon concentrations. Plasma insulin and C-peptide concentrations remained low and rebounded at the end of the infusions. In the same subjects, beta-endorphin produced elevations of plasma glucose, insulin, C-peptide, and glucagon. When the combined hormonal infusion was given to obese subjects, the plasma epinephrine and beta-endorphin concentrations rose to values not significantly different from those in normal weight subjects. However, there was a dramatic increase in plasma glucose exceeding 200 mg/dL (11.1 mmol/L), which remained elevated 30 min after the infusion. The glucagon response was not greater than the sum of the single effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

[Perspectives on atypical routes of insulin administration. Oral, rectal, and nasal routes].

The present review concerns the current possibilities of insulin administration through the oral, rectal or nasal routes. The use of vehicle such as liposomes or various polymers protecting the hormone against the digestive enzymes allowed to improve the absorption of insulin after its oral administration. Moreover, the use of various surfactants favours the resorption of insulin through the intestinal, rectal and nasal mucosae. However until now, none of these routes has sufficient reliability and reproducibility to be considered for routine treatment of diabetes mellitus.

Administration, Oral↗
PubMed1988

[Prostaglandins, insulin secretion and diabetes mellitus].

The islets of Langerhans have the enzymatic equipment permitting the synthesis of the metabolites of arachidonic acid: cyclo-oxygenase and lipo-oxygenase. Numerous studies have shown that cyclo-oxygenase derivatives, mainly PGE2, reduce the insulin response to glucose whereas lipo-oxygenase derivatives, mainly 15-HPETE, stimulate insulin secretion. So, for instance, drugs that increase prostaglandins synthesis as colchicine or furosemide inhibit insulin secretion while non steroid anti-inflammator drugs, mainly salicylates, which inhibit cyclo-oxygenase, enhance the insulin response to various stimuli. In type-2 (non insulin-dependent) diabetes, an increased sensitivity to endogenous prostaglandins has been proposed as a possible cause for the insulin secretion defect which characterizes this disease. Play in favor of this hypothesis the fact that the administration of PGE inhibits the insulin response to arginine in type-2 diabetics but not in normal subject and the fact that the administration of salicylates could improve the insulin response to glucose in some of these patients.

Animals↗
PubMed1987

Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man.

To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin (100 micrograms X h-1), basal insulin secretion was replaced by a continuous insulin infusion (0.2 mU X kg-1 X min-1), and glucagon was infused intravenously in two conditions at random: either continuously (125 ng X min-1) or intermittently (812.5 ng X min-1, with a switching on/off length of 2/11 min). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3-3H]glucose infusion allowed us to study glucose turnover. While basal plasma glucagon levels were similar in both conditions (122 +/- 31 vs. 115 +/- 18 pg X ml-1), they plateaued at 189 +/- 38 pg X ml-1 during continuous infusion and varied between 95 and 501 pg X ml-1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, did not prevent the so-called "evanescent" effect of glucagon on blood glucose, and after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucagonemia in normal man fails to increase hepatic glucose production.

Adult↗
PubMed1987

Pharmacokinetics and pharmacological properties of two galenical preparations of glibenclamide, HB419 and HB420, in non insulin-dependent (type 2) diabetes.

The pharmacokinetics and pharmacological properties of a new micronized preparation of glibenclamide (HB420, 3.5 mg/tablet) were compared to those of the classical formulation (HB419, 5 mg/tablet) in non insulin-dependent diabetics. In a double-blind cross-over randomized acute study, blood glucose, plasma insulin, C-peptide and glibenclamide levels were determined in 10 patients after a standardized breakfast taken 15 min following the ingestion of 1.1 +/- 0.2 tablets of HB419 or HB420. Plasma glibenclamide levels rose faster, the peak value was higher (637 +/- 154 versus 411 +/- 76 nmol/l, p less than 0.05) and the area under the curve from 0 to 240 min was 35% greater (p less than 0.05) on HB420 than on HB419. Nevertheless, the post-breakfast hormonal and metabolic changes were similar with both preparations. In a single-blind cross-over chronic study, 12 patients were treated during 3 successive 6 to 8-week periods--HB419, HB420, HB419--with glibenclamide at a dose of 1.8 +/- 0.3 tablets/day. While fasting blood glucose concentrations remained unchanged throughout the study, postprandial levels decreased from 10.9 +/- 0.8 mmol/l during the HB419 pre-period to 9.2 +/- 0.6 mmol/l during HB420 (p less than 0.02) and rose again up to 10.4 +/- 0.8 mmol/l during the last HB419 period (p less than 0.05). Similarly HbA1c decreased slightly from 7.4 +/- 0.3 to 7.2 +/- 0.4% (NS) and increased again up to 7.8 +/- 0.4% (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1986

Remarkable metabolic availability of oral glucose during long-duration exercise in humans.

It was reported previously that glucose ingestion prior to or at the beginning of muscular exercise was a readily available metabolic substrate. The aim of this study was to see what percentage of carbohydrate utilization can be covered by glucose ingested regularly during exercise. Male healthy volunteers exercised for 285 min at approximately 45% of their individual maximal O2 uptake on a 10% uphill treadmill. After 15 min adaptation to exercise they received either 200 g (group G 200) or 400 g (group G 400) glucose (0.25 g X ml H2O-1) orally in eight equal doses repeated every 30 min (G 200 = 8 X 25 g, n = 4; G 400 = 8 X 50 g, n = 4). Indirect calorimetry was used to evaluate carbohydrate and lipid oxidation. Naturally labeled [13C]glucose was used to follow the oxidation of the exogenous glucose. Total carbohydrate oxidation was 341 +/- 22 and 332 +/- 32 g, lipid oxidation was 119 +/- 8 and 105 +/- 5 g, and exogenous glucose oxidation was 137 +/- 4 and 227 +/- 13 g (P less than 0.005) in groups G 200 and G 400, respectively. Endogenous glucose oxidation was about half in G 400 of what it was in G 200: 106 +/- 27 vs. 204 +/- 24 g (P less than 0.02). During the last hour of exercise, exogenous oxidation represented 55.3 and 87.5% of total carbohydrate oxidation for groups G 200 and G 400, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1986

Insulin oscillations per se do not affect glucose turnover parameters in normal man.

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.

Adult↗
PubMed1985

Insulin-stimulated glucose disposal is not increased in anorexia nervosa.

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.

3-Hydroxybutyric Acid↗
PubMed1984

Glipizide increases plasma insulin but not C-peptide level after a standardized breakfast in type 2 diabetic patients.

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)

Blood Glucose↗
PubMed1984

Glibenclamide pharmacokinetics in acarbose-treated type 2 diabetics.

A single dose of glibenclamide 5 mg was administered to six Type 2 diabetics, randomly treated for 7 days either with acarbose (3 X 100 mg daily) or with placebo. The serum concentration of the drug was measured for 10 h. Peak concentrations, times-to-peak concentration, elimination half-lives and the extent of bioavailability of the drug were not significantly modified by acarbose. The combined administration of glibenclamide and acarbose resulted in a modest improvement in the blood glucose profile after breakfast and lunch, together with a significant diminution in plasma insulin. Thus, acarbose appears a useful additional treatment for Type 2 diabetics already receiving sulphonylurea derivatives.

Acarbose↗
PubMed1984

Effect of physical training on utilization of a glucose load given orally during exercise.

The effect of a 6-wk training period on the oxidation of a 100-g glucose load given orally during exercise was investigated in six healthy male volunteers. The subjects were submitted before and 24 h after the training program to a 105-min exercise bout (performed at about 40% of the pretraining VO2max) followed by a 90-min resting period. Naturally labeled [13C]glucose was given 15 min after the beginning of exercise. Exogenous glucose oxidation was derived from 13CO2 measurements in expired air, and total glucose and lipid oxidation were evaluated by indirect calorimetry. Training (60-min bicycling 5 days a week at 30-40% VO2max) resulted in a 29% increase in VO2max. During the 15 min of exercise that preceded glucose ingestion, the rate of total carbohydrate oxidation was slightly decreased after training, whereas the rate of lipid oxidation was slightly increased. Training did not affect the response of blood glucose, plasma insulin, or plasma free fatty acids to the glucose ingested during exercise; in contrast, the circulating levels of epinephrine, glycerol, and lactate were significantly reduced after training. Substrate utilization measurements revealed similar oxidation rates of carbohydrates (106.9 +/- 2.7 before vs. 100.2 +/- 4.7 g/3 h after training) and of lipids. However, detailed analysis revealed a significant 17% increase in exogenous glucose oxidation, thus indicating a significant sparing of endogenous carbohydrates. In conclusion, physical training induces a modest but significant increase in the oxidation of an oral load of glucose given during subsequent exercise of moderate intensity, a phenomenon reinforcing the sparing of endogenous carbohydrate stores.

Administration, Oral↗