Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 325 records · Page 18Linked to original sources

PubMed1995

Exogenous glucose oxidation during exercise in relation to the power output.

In order to study the influence of the power output on the oxidation rate of exogenous glucose and on the contribution of the various substrates to the energy demand, we combined the use of artificially enriched 13C-glucose with classical indirect calorimetry during uphill treadmill exercise. Six young male healthy subjects underwent three exercise bouts, in a randomized order and at least two weeks apart, at a low (45% VO2max, 1822 +/- 194 ml O2/min for 4 hours), moderate (60% VO2max, 2582 +/- 226 ml O2/min for 3 hours), and high intensity (75% VO2max, 3036 +/- 287 ml O2/min for 2 hours). After 10 min of exercise, each subject ingested 100 g of artificially 13C-labelled glucose dissolved in 400 ml of water. Over the four hours of the exercise at 45% VO2max, the amount of exogenous glucose oxidized was 89.5 +/- 5.9 g from the 100 g ingested. In all exercise bouts, the oxidation of exogenous glucose already began during the first 30 min after ingestion and peaked at 120 min. The maximum oxidation rates averaged 0.64 +/- 0.07, 0.75 +/- 0.04, and 0.63 +/- 0.08 g/min, and the mean amounts of exogenous glucose oxidized over the first two hours averaged 51.7 +/- 8.0, 61.5 +/- 6.6 and 50.9 +/- 8.45 g, at 45, 60 and 75% VO2max respectively. The contribution of the oxidation of exogenous glucose to the total energy supply progressively decreased when the power output increased, from 19.6 to 12.2%. In the meantime, the contribution of total carbohydrates (exogenous+endogenous) progressively increased from 55.1 to 77.8% while the contribution of lipids decreased from 35.5 to 16.6%. In conclusion, exogenous glucose ingested during exercise is largely oxidized and strongly contributes to the energy supply. The oxidation rate first increases with the power output, but levels off or even decreases at high intensity exercise.

Adult↗

PubMed1995

Short administration of metformin improves insulin sensitivity in android obese subjects with impaired glucose tolerance.

In a double-blind, randomized, cross-over study, the metabolic effects of a short treatment with metformin (2 x 850 mg day-1 for 2 days and 850 mg 1 h before evaluation) were compared to those of placebo in 15 obese subjects (BMI: 33.2 +/- 0.9 kg m-2), with abdominal distribution of adipose tissue and impaired glucose tolerance. An intravenous glucose tolerance test (0.3 g glucose kg-1) was performed after each period of treatment. Areas under the curve (AUC0-180 min) were calculated for plasma glucose, insulin, and C-peptide levels. Glucose tolerance was estimated by the coefficient of glucose assimilation (KG). Insulin sensitivity (SI) and glucose effectiveness (SG) indices were calculated using Bergman's minimal model. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide levels and insulin metabolic clearance rate (MCR) was estimated by dividing AUC 1SR by AUC insulin. Fasting plasma insulin levels were reduced after metformin (89.3 +/- 15.9 vs 112.4 +/- 24.3 pmol l-1; p = 0.04). AUC glucose, KG and SG were similar in both tests. However, AUC insulin was reduced (39.7 +/- 6.5 vs 51.8 +/- 10.4 nmol min l-1; p = 0.02), while SI (6.98 +/- 1.14 vs 4.61 +/- 0.42 10(-5) min-1 pmol-1 l; p = 0.03) and insulin MCR (715 +/- 116 vs 617 +/- 94 ml min-1 m-2; p = 0.03) were increased after metformin. The demonstration that metformin rapidly improves insulin sensitivity should encourage further research to evaluate the long-term effects of metformin in android obese subjects with impaired oral glucose tolerance.

Adult↗

PubMed1995

24-hour glucose profiles during continuous or oscillatory insulin infusion. Demonstration of the functional significance of ultradian insulin oscillations.

Under basal and stimulated conditions, normal insulin secretion oscillates with periods in the ultradian 100-150-min range. To test the hypothesis that oscillatory insulin delivery is more efficient in reducing blood glucose levels than continuous administration, nine normal young men were each studied on two occasions during a 28-h period including a period of polygraphically recorded sleep. Endogenous insulin secretion was suppressed by somatostatin, a constant intravenous glucose infusion was administered, and exogenous insulin was infused either at a constant rate or in a sinusoidal pattern with a period of 120 min. The mean glucose level over the 28-h period was 0.72 +/- 0.31 mmol/liter lower when insulin was infused in an oscillatory pattern than when the rate of infusion was constant (P < 0.05). The greater hypoglycemic effect of oscillatory versus constant infusion was particularly marked during the daytime, with the difference averaging 1.04 +/- 0.38 mmol/liter (P < 0.03). Serum insulin levels tended to be lower during oscillatory than constant infusion, although the same amount of exogenous insulin was administered under both conditions. Ultradian insulin oscillations appear to promote more efficient glucose utilization.

Adult↗

PubMed1995

Postgastroplasty recovery of ideal body weight normalizes glucose and insulin metabolism in obese women.

To study the metabolic effects of normalizing body weight, a frequently sampled iv glucose tolerance test (0.3 g/kg) was performed before [body mass index (BMI), 37.7 +/- 0.5 kg/m2] and 14 +/- 2 months after successful gastroplasty (BMI, 23.7 +/- 0.6 kg/m2) in eight obese women and, for comparison, in eight age- and weight-matched nonobese control women (BMI, 23.6 +/- 0.7 kg/m2). All subjects had normal oral glucose tolerance. The insulin secretion rate (ISR) was derived by deconvolution of plasma C-peptide levels and the insulin MCR (MCRI) by dividing the 0-180 min area under the curve (AUC) of ISR by that of plasma insulin levels (IRI). The insulin sensitivity index (SI) and the glucose effectiveness index (SG) were calculated using Bergman's minimal model. Before gastroplasty, obese subjects showed higher AUC-IRI (P < 0.001) and AUC-ISR (P < 0.02), lower MCRI (P < 0.005) and SI (P < 0.002), but similar SG values, compared to nonobese controls. After gastroplasty, the AUC-IRI dramatically decreased, due to both a reduction of AUC-ISR (from 58,252 +/- 8,437 to 36,675 +/- 4,274 pmol; P < 0.05) and an increase in MCRI (from 658 +/- 117 to 1,299 +/- 127 mL/min.m-2; P < 0.02). SI significantly rose from 4.74 +/- 0.74 to 9.15 +/- 0.96 10(-5) min-1/pmol.L (P < 0.01), whereas SG remained unchanged. All of these parameters became similar to those in nonobese controls (respectively, 32,522 +/- 3,458, 1,180 +/- 101, and 8.48 +/- 1.25; all P = NS). In conclusion, after gastroplasty-induced normalization of body weight, postobese women recover normal insulin secretion, clearance, and action on glucose metabolism.

Adult↗

PubMed1995

Modified glucagon test allowing simultaneous estimation of insulin secretion and insulin sensitivity: application to obesity, insulin-dependent diabetes mellitus, and noninsulin-dependent diabetes mellitus.

The aim of this study was to describe an adaptation of the glucagon test allowing the simultaneous characterization of insulin secretion and sensitivity. A glucagon test (1 mg/m2) was performed in healthy subjects (n = 11), obese patients (n = 5), insulin-dependent diabetics (n = 9), nonobese noninsulin-dependent diabetics (n = 7), and overweight noninsulin-dependent diabetics (n = 8). Previously, they had been connected to the Biostator, modified for continuous blood collection. Endogenous insulin secretion induced by glucagon was derived from integrated C-peptide concentrations. An index of insulin sensitivity was obtained by dividing the rate of decrease in blood glucose by the total amount of insulin entering the circulation (secreted+infused by the Biostator). The indices of insulin sensitivity obtained in the above groups of subjects were, respectively, 0.064 +/- 0.006, 0.030 +/- 0.006, 0.037 +/- 0.007, 0.021 +/- 0.006, and 0.016 +/- 0.002 mmol/L.U.min (P < 0.001). The estimated insulin secretion values in the 20 min following glucagon injection were, respectively, 0.38 +/- 0.05, 0.65 +/- 0.08, 0.05 +/- 0.01, 0.26 +/- 0.15, and 0.30 +/- 0.07 U (P < 0.001). The insulin sensitivity index obtained from this test correlated with the glucose MCR obtained from a euglycemic glucose clamp (r = 0.816; P < 0.001; n = 12). C-Peptide levels after glucagon administration were also significantly correlated with the estimated endogenous insulin secretion (r = 0.808; P < 0.001; n = 30). This adaptation of the classical glucagon test is an efficient and simple method to simultaneously evaluate insulin secretion and insulin sensitivity.

Adult↗

PubMed1995

Antihyperglycaemic agents. Drug interactions of clinical importance.

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) affects middle-aged or elderly people who frequently have several other concomitant diseases, especially obesity, hypertension, dyslipidaemias, coronary insufficiency, heart failure and arthropathies. Thus, polymedication is the rule in this population, and the risk of drug interactions is important, particularly in elderly patients. The present review is restricted to the interactions of other drugs with antihyperglycaemic compounds, and will not consider the mirror image, i.e. the interactions of antihyperglycaemic agents with other drugs. Oral antihyperglycaemic agents include sulphonylureas, biguanides--essentially metformin since the withdrawn of phenformin and buformin--and alpha-glucosidase inhibitors, acarbose being the only representative on the market. These drugs can be used alone or in combination to obtain better metabolic control, sometimes with insulin. Drug interactions with antihyperglycaemic agents can be divided into pharmacokinetic and pharmacodynamic interactions. Most pharmacokinetic studies concern sulphonylureas, whose action may be enhanced by numerous other drugs, thus increasing the risk of hypoglycaemia. Such an effect may result essentially from protein binding displacement, inhibition of hepatic metabolism and reduction of renal clearance. Reduction of the hypoglycaemic activity of sulphonylureas due to pharmacokinetic interactions with other drugs appears to be much less frequent. Drug interactions leading to an increase in plasma metformin concentrations, mainly by reducing the renal excretion or the hepatic metabolism of the biguanide, should be avoided to limit the risk of hyperlactaemia. Owing to its mode of action, pharmacokinetic interferences with acarbose are limited to the gastrointestinal tract, but have not been extensively studied yet. Pharmacodynamic interactions are quite numerous and may result in a potentiation of the hypoglycaemic action or, conversely, in a deterioration of blood glucose control. Such interactions may be observed whatever the type of antidiabetic treatment. They result from the intrinsic properties of the coprescribed drug on insulin secretion and action, or on a key step of carbohydrate metabolism. Finally, a combination of 2 to 3 antihyperglycaemic agents is common for treating patients with NIDDM to benefit from the synergistic effect of compounds acting on different sites of carbohydrate metabolism. Possible pharmacokinetic interactions between alpha-glucosidase inhibitors and classical antidiabetic oral agents should be better studied in the diabetic population.

Administration, Oral↗

PubMed1995