The degree/rapidity of the metabolic deterioration following interruption of a continuous subcutaneous insulin infusion is influenced by the prevailing blood glucose Level.
; Scheen, André ; Lefebvre, Pierre
in Journal of Clinical Endocrinology and Metabolism (1996), 81(5), 1975-8
This study aims at investigating the influence of the prevailing blood glucose level on the metabolic deterioration that follows a nocturnal interruption of a continuous sc insulin infusion (CSII ... [more ▼]
This study aims at investigating the influence of the prevailing blood glucose level on the metabolic deterioration that follows a nocturnal interruption of a continuous sc insulin infusion (CSII). Fifteen CSII-treated, C-peptide negative, diabetic patients have been studied CSII was interrupted from 2300 h to 0500 h. Blood was collected hourly from 2200 h to 0600 h. According to blood glucose (BG) levels at 2300 h, patients were classified as hypoglycemic (BG between 1.5 and 2.5 mmol/L, n = 5), normoglycemic (BG between 4.0 and 8.0 mmol/L, n = 5), or hyperglycemic (BG between 9.0 and 15.0 mmol/L, n = 5). At 2300 h, BG (mean +/- SEM) was 1.9 +/- 0.1, 6.2 +/- 0.7 and 11.2 +/- 1.0 mmol/L, respectively. After 6 h of CSII interruption, BG increased to 13.5 +/- 1.3, 14.1 +/- 1.2, and 19.4 +/- 1.2 mmol/L, respectively. At 2300 h, plasma 3-OH-butyrate levels were similar in the three groups (around 150 micromol/L). At 0500 h, significantly higher values were obtained for hyperglycemic (1460 +/- 127 micromol/L) than for normoglycemic (868 +/- 150 micromol/L) or hypoglycemic (837 +/- 80 micromol/L) patients. Enhanced lipolysis in initially hyperglycemic patients may contribute to accelerated ketogenesis and metabolic degradation. In conclusion, the metabolic deterioration that follows CSII interruption is influenced by the initial metabolic situation. Hypoglycemic patients deteriorate more rapidly, and hyperglycemic patients suffer a more important degradation. The latter are prone to rapid ketoacidosis if accidental CSII interruption occurs. [less ▲]Detailed reference viewed: 10 (1 ULg)
Alterations in the ultradian oscillations of insulin secretion and plasma glucose in aging.
Scheen, André ; ; et al
in Diabetologia (1996), 39(5), 564-72
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 ... [more ▼]
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. [less ▲]Detailed reference viewed: 18 (0 ULg)
Clinical pharmacokinetics of metformin.
in Clinical Pharmacokinetics (1996), 30(5), 359-71
The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus (NIDDM). Considerable renewal of interest in this ... [more ▼]
The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus (NIDDM). Considerable renewal of interest in this drug has been observed in recent years. Metformin can be determined in biological fluids by various methods, mainly using high performance liquid chromatography, which allows pharmacokinetic studies in healthy volunteers and diabetic patients. Metformin disposition is apparently unaffected by the presence of diabetes and only slightly affected by the use of different oral formulations. Metformin has an absolute oral bioavailability of 40 to 60%, and gastrointestinal absorption is apparently complete within 6 hours of ingestion. An inverse relationship was observed between the dose ingested and the relative absorption with therapeutic doses ranging from 0.5 to 1.5 g, suggesting the involvement of an active, saturable absorption process. Metformin is rapidly distributed following absorption and does not bind to plasma proteins. No metabolites or conjugates of metformin have been identified. The absence of liver metabolism clearly differentiates the pharmacokinetics of metformin from that of other biguanides, such as phenformin. Metformin undergoes renal excretion and has a mean plasma elimination half-life after oral administration of between 4.0 and 8.7 hours. This elimination is prolonged in patients with renal impairment and correlates with creatinine clearance. There are only scarce data on the relationship between plasma metformin concentrations and metabolic effects. Therapeutic levels may be 0.5 to 1.0 mg/L in the fasting state and 1 to 2 mg/L after a meal, but monitoring has little clinical value except when lactic acidosis is suspected or present. Indeed, when lactic acidosis occurs in metformin-treated patients, early determination of the metformin plasma concentration appears to be the best criterion for assessing the involvement of the drug in this acute condition. After confirmation of the diagnosis, treatment should rapidly involve forced diuresis or haemodialysis, both of which favour rapid elimination of the drug. Although serious, lactic acidosis due to metformin is rare and may be minimised by strict adherence to prescribing guidelines and contraindications, particularly the presence of renal failure. Finally, only very few drug interactions have been described with metformin in healthy volunteers. Plasma levels may be reduced by guar gum and alpha-glucosidase inhibitors and increased by cimetidine, but no data are yet available in the diabetic population. [less ▲]Detailed reference viewed: 133 (0 ULg)
Changes in breath 13CO2/12CO2 during exercise of different intensities.
; Pirnay, Freddy ; et al
in Journal of Applied Physiology (Bethesda, Md. : 1985) (1996), 81(3), 1096-102
The measurement of breath 13CO2/12CO2 is commonly used during exercise to evaluate the oxidation rate of exogenous carbohydrates enriched in 13C. The aim of this study was to investigate whether exercise ... [more ▼]
The measurement of breath 13CO2/12CO2 is commonly used during exercise to evaluate the oxidation rate of exogenous carbohydrates enriched in 13C. The aim of this study was to investigate whether exercise itself affects the 13C/12C ratio in expired air CO2 in relation to exercise intensity. The relative abundance of 13C and 12C in expired air CO2 was determined by isotoperatio mass spectrometry and expressed as delta 13C (in %o) by using Craig's formula and calibrated standards. Five healthy young men exercised on a treadmill after an overnight fast during > or = 105 min on four occasions and in a randomized order. Work rates were performed at approximately 30, 45, 60, and 75% of their maximal O2 uptake (VO2max). Delta 13C in expired air CO2 and respiratory exchange ratio (RER) were determined every 15 or 30 min during exercise. At 30 and 45% VO2max, a slight and not statistically significant increase in delta 13C was observed at 30 min. In contrast, at 60 75% VO2max, the rise was statistically significant and averaged 0.83 and 0.99%o, respectively. Average delta 13C (between 0 and 105 min) progressively increased with the intensity of exercise. Individual values of delta 13C and RER were positively correlated (r = 0.653, P = 0.002) as were values of delta 13C and endogenous carbohydrates utilized (r = 0.752, P < 0.001). Factitious or "pseudooxidation" of a 13C-enriched exogenous glucose load (indeed noningested) was calculated from the changes in expired air delta 13C. Over the whole period of exercise it was not statistically significant at 30 and 40% VO2max. However, over the first 60 min of exercise, such pseudooxidation of exogenous glucose was significant at 30 and 45% VO2max. In conclusion, by modifying the mix of endogenous substrates oxidized, exercise at 60% VO2max and above significantly increases the 13C/12C ratio in expired air CO2. At these intensities, this could lead to overestimation of the oxidation of 13C-labeled substrates given orally. At lower intensities of exercise, such overestimation is much smaller an affects mainly the values recorded during the initial part of the exercise bout. [less ▲]Detailed reference viewed: 17 (0 ULg)
Assessment of residual insulin secretion in diabetic patients using the intravenous glucagon stimulatory test: methodological aspects and clinical applications.
Scheen, André ; ; Lefebvre, Pierre
in Diabètes & Métabolism (1996), 22(6), 397-406
Defective insulin secretion plays a crucial role in insulin-dependent (Type 1) and non-insulin-dependent (Type 2) diabetes mellitus as well as in many secondary forms of the disease. Glucagon is a potent ... [more ▼]
Defective insulin secretion plays a crucial role in insulin-dependent (Type 1) and non-insulin-dependent (Type 2) diabetes mellitus as well as in many secondary forms of the disease. Glucagon is a potent stimulus for the islet beta-cell, and intravenous bolus injection of 1 mg glucagon has been widely used to assess endogenous insulin secretion for clinical or research purposes. Plasma C-peptide levels (less commonly insulin) are usually measured immediately before and 6 min after glucagon injection. The C-peptide response to glucagon is well-correlated with the beta-cell response to mixed meals or other stimuli commonly used to characterize endogenous insulin secretion (oral or intravenous glucose, standard meals, arginine, etc.) and has the advantage of shorter duration and simple standardization. The glucagon test shows good intra-subject reproducibility, although in diabetic patients it may be influenced by variable prevailing blood glucose levels. Several applications of the glucagon test have been developed. In Type 1 diabetes, the glucagon test has been used to discriminate between patients with and without residual insulin secretion. This can be especially important during the first few months, or even years, following initiation of insulin therapy when attempts to stop the immunological destruction of the beta-cell are made. Assessment of endogenous insulin secretion is also important after pancreas or islet transplantation. In patients with Type 2 diabetes mellitus, in which residual endogenous insulin secretion is common, characterization of the disease may help in the choice of therapy for the individual patient (insulin, sulphonylureas or combined therapy). Thus, the glucagon test is a simple, reliable and useful tool for clinical evaluation of diabetes mellitus. [less ▲]Detailed reference viewed: 29 (1 ULg)
Relationships between sleep quality and glucose regulation in normal humans.
Scheen, André ; ; et al
in American Journal of Physiology (1996), 271(2 Pt 1), 261-70
To define the effects of sleep on glucose regulation, we analyzed plasma glucose levels, insulin secretion rates (ISR), and plasma growth hormone and cortisol levels in normal subjects receiving a ... [more ▼]
To define the effects of sleep on glucose regulation, we analyzed plasma glucose levels, insulin secretion rates (ISR), and plasma growth hormone and cortisol levels in normal subjects receiving a constant glucose infusion during nocturnal sleep, nocturnal sleep deprivation, and daytime recovery sleep. Plasma glucose and ISR markedly increased during early nocturnal sleep and returned to presleep levels during late sleep. These changes in glucose and ISR appeared to reflect the predominance of slow-wave (SW) stages in early sleep and of rapid-eye-movement and wake stages in late sleep. Major differences in glucose and ISR profiles were observed during sleep deprivation as glucose and ISR remained essentially stable during the first part of the night and then decreased significantly, despite the persistence of bed rest and constant glucose infusion. During daytime recovery sleep, SW stages were increased, glucose levels peaked earlier than during nocturnal sleep, and the decreases of glucose and ISR in late sleep were reduced by one-half. Thus sleep has important effects on brain and tissue glucose utilization, suggesting that sleep disturbances may adversely affect glucose tolerance. [less ▲]Detailed reference viewed: 22 (1 ULg)
Usefulness of fluoxetine in obese non-insulin-dependent diabetics: a multicenter study.
; ; et al
in Obesity Research (1996), 4(4), 391-6
Weight reduction is essential in the management of most non-insulin-dependent diabetics, but this therapeutical goal is difficult to obtain. In this double-blind parallel study, 82 non-insulin-dependent ... [more ▼]
Weight reduction is essential in the management of most non-insulin-dependent diabetics, but this therapeutical goal is difficult to obtain. In this double-blind parallel study, 82 non-insulin-dependent diabetics, moderately obese (BMI = 30 - 39 kg/m2), were given for an 8-week period either placebo (P) or fluoxetine (F), a specific serotonin reuptake inhibitor, in addition to their usual antidiabetic treatment. Thirty-nine of them received 60 mg fluoxetine a day and 43 were given the placebo. At admission, both groups had similar weight excess, metabolic control and serum lipid values. In comparison with the P-treated subjects, those treated with fluoxetine (F) lost more weight after 3 weeks (-1.9 vs. -0.7 kg, p < -0.0009) and after 8 weeks (-3.1 vs. -0.9 kg, p < 0.0007). Fasting blood glucose decreased in group F after 3 weeks (-1.5 vs -0.4 mmol/L, p < 0.003) and after 8 weeks (-1.7 vs. -0.02 mmol/L, p < 0.0004). HbAlc decreased from 8.5% to 7.7% in group F and from 8.6% to 8.3% in group P (p = 0.057). Mean triglyceride level was also reduced in group F after 8 weeks (p = 0.042). Fasting C-peptide did not change in either group, but fasting insulin values decreased in group F after 3 weeks (p < 0.02) and after 8 weeks (p < 0.05). The insulin/C-peptide molar ratio decreased significantly in group F after 3 weeks (p < 0.04) and after 8 weeks (p < 0.05) in comparison with group P. The drug was generally well tolerated and no major side effects were reported. In conclusion, the addition of fluoxetine to the usual oral hypoglycemic agent therapy might be beneficial in obese non-insulin-dependent diabetics, at least on a short-term basis. [less ▲]Detailed reference viewed: 56 (0 ULg)
Le diabete non insulinodependant: de la physiopathologie au traitement.
Scheen, André ; Lefebvre, Pierre
in Bulletin et Mémoires de l'Académie Royale de Médecine de Belgique (1996), 151(7-9), 395-402402-5
Non-insulin-dependent (or type 2) diabetes mellitus is a common, underdiagnosed and growing disease in our society. It is responsible for increased morbidity and mortality and represents an important ... [more ▼]
Non-insulin-dependent (or type 2) diabetes mellitus is a common, underdiagnosed and growing disease in our society. It is responsible for increased morbidity and mortality and represents an important public health problem. This polygenic disease is often expressed late in life and its evolution is accelerated by environmental factors leading to obesity. It combines defects in both insulin secretion and insulin action, and such defects are present in various proportions according to the type of patient and the stage of the disease. Diet and physical activity recommendations are the basis of the treatment. Current pharmacological approaches aim at improving insulin secretion and/or insulin cellular action. After secondary failure to oral drugs, insulin therapy should be initiated, the patient becoming "insulin-requiring". A synergy should be searched in the combination of various therapeutic modalities in order to improve the glycaemic control. [less ▲]Detailed reference viewed: 67 (0 ULg)
Mise au point medicale avant gastroplastie: indications et contre-indications.
in Revue Médicale de Bruxelles (1996), 17(4), 232-5
Because of the common failure of the various medical procedures used for the treatment of morbid obesity, surgeons have searched alternatives among which gastroplasty appears to offer now the best ... [more ▼]
Because of the common failure of the various medical procedures used for the treatment of morbid obesity, surgeons have searched alternatives among which gastroplasty appears to offer now the best efficacy/safety ratio. Such approach has become more and more popular in our country, but success is almost highly variable from patient to patient. A careful medical assessment is necessary before performing gastroplasty. It mainly aims at choosing the appropriate indications (failure of previous well-applied medical therapy, exclusion of any hormonal cause of obesity, presence of complications due to weight excess, ...) and at excluding cardiovascular (unstable coronaropathy, carotid stenosis, ...), digestive (recurrent oesophagitis, ...) or psychiatric contra-indications. Such medical assessment before gastroplasty should allow to increase the success rate and to reduce the incidence of complications after the surgical procedure. [less ▲]Detailed reference viewed: 65 (0 ULg)
Insulin action in man.
Scheen, André ; Lefebvre, Pierre
in Diabètes & Métabolism (1996), 22(2), 105-10
Insulin action is crucial for the regulation of glucose metabolism. Insulin plays a key role in suppressing endogenous glucose production by the liver, both in fasting and postprandial states. Insulin is ... [more ▼]
Insulin action is crucial for the regulation of glucose metabolism. Insulin plays a key role in suppressing endogenous glucose production by the liver, both in fasting and postprandial states. Insulin is also necessary for the maintenance of normal rates of glucose oxidation and storage in insulin-sensitive tissues and for the prevention of excessive gluconeogenic substrate production. Various methods have been developed to assess insulin action in vivo, essentially at liver and muscle sites. Such methods evaluate the effect of exogenous or endogenous insulin, using respectively the open-loop approach (interruption of the feedback loop by inhibiting endogenous insulin secretion) or the closed-loop approach (mathematical modelling of the insulin-glucose feedback loop). Knowledge of the successive steps of cellular insulin action has markedly improved during the last ten years. Preceptor, receptor and postreceptor levels need to be considered since they may be affected in insulin-resistant states. This general progress in the understanding of insulin action in man improves our approach to the complex pathophysiology of non-insulin-dependent diabetes mellitus and opens up new prospects for treatment of the insulin-resistant syndrome which is associated with several atherosclerotic risk factors. [less ▲]Detailed reference viewed: 14 (0 ULg)
Glucagon-induced plasma C-peptide response in diabetic patients. Influence of body weight and relationship to insulin requirement.
Scheen, André ; ; Lefebvre, Pierre
in Diabètes & Métabolism (1996), 22(6), 455-8Detailed reference viewed: 24 (0 ULg)
Exercise in the Management of Non-Insulin-Dependent (Type 2) Diabetes Mellitus
; Scheen, André ;
in International Journal of Obesity & Related Metabolic Disorders (1995), 19(Suppl 4), 58-61Detailed reference viewed: 16 (2 ULg)
Le rôle du foie dans l'homéostasie glucidique: une relecture des travaux de Claude Bernard
; PAQUOT, Nicolas ; SCHEEN, André
in Journées Annuelles de Diabetologie de l'Hôtel-Dieu (1995)Detailed reference viewed: 298 (0 ULg)
Aspects hémodynamiques de l'insulinorésistance: des concepts théoriques à la thérapeutique.
Paquot, Nicolas ; SCHEEN, André ;
in Médecine et Hygiène (1995), 53Detailed reference viewed: 5 (0 ULg)
Etiologie et physiopathologie du diabète de type 2.
SCHEEN, André ; PAQUOT, Nicolas ;
in Problèmes Actuels d'Endocrinologie et de Nutrition (1995), 10Detailed reference viewed: 23 (0 ULg)
Comment explorer la sensibilite a l'insuline chez l'homme?
Scheen, André ; Paquot, Nicolas ; Letiexhe, Michel et al
in Annales d'Endocrinologie (1995), 56(5), 523-30
The two most widely used methods for studying insulin sensitivity in man are the euglycaemic hyperinsulinaemic clamp and the intravenous glucose tolerance test with minimal model assessment. The glucose ... [more ▼]
The two most widely used methods for studying insulin sensitivity in man are the euglycaemic hyperinsulinaemic clamp and the intravenous glucose tolerance test with minimal model assessment. The glucose clamp is the reference method, well validated and easy to interpret, which allows various extensions to the basic experimental procedure in order to obtain more valuable information on the specific effects of insulin on the various aspects of glucose metabolism. However, it is time-consuming and labour-intensive. In contrast, the intravenous glucose tolerance test is easier to perform, but its interpretation is much more difficult and requires a modeling approach called the "minimal model". If the intravenous glucose tolerance test probably represents a good screening test, mainly on a population basis, the glucose clamp still remains the gold standard method to study insulin sensitivity in man. [less ▲]Detailed reference viewed: 77 (0 ULg)
Hepatic glucose metabolism after fructose ingestion in NIDDM and obses non diabetic subjects.
PAQUOT, Nicolas ; ; et al
in Diabetes (1995), 44(suppl 1), 254Detailed reference viewed: 5 (0 ULg)
Métabolisme hépatique du glucose après ingestion de fructose chez des sujets obèses non diabétiques et diabétiques non insulinodépendants
PAQUOT, Nicolas ; ; et al
in Diabète & Métabolisme (1995), 21(suppl),Detailed reference viewed: 28 (2 ULg)
Glucose metabolism in obese subjects: lessons from OGTT, IVGTT and clamp studies.
Scheen, André ; Paquot, Nicolas ; Letiexhe, Michel et al
in International Journal of Obesity & Related Metabolic Disorders (1995), 19 Suppl 3
Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for ... [more ▼]
Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for insulin resistance by peripheral hyperinsulinism, the latter resulting from both increased insulin secretion and reduced insulin clearance. Impaired glucose tolerance is observed when insulin resistance is associated to impaired first-phase insulin response, which results in a significant increase in plasma glucose levels and a late insulin hyperresponsiveness. Both hyperinsulinaemia and hyperglycaemia are then able to overcome peripheral insulin resistance and impaired glucose disposal. When a more marked defect in insulin secretion is present, hyperglycaemia progresses, probably due to an additional participation of impaired suppression of hepatic glucose output. Overt diabetes then occurs with persistent post-absorptive hyperglycaemia. All these abnormalities can be reversed after a marked weight loss and recovery of ideal body weight, arguing for acquired rather than inherited metabolic defects in presence of morbid obesity. If a sufficient weight reduction can not be obtained, pharmacological approaches may be considered to improve insulin resistance of obese subjects, especially those with impaired glucose tolerance or overt diabetes. [less ▲]Detailed reference viewed: 44 (2 ULg)
24-hour glucose profiles during continuous or oscillatory insulin infusion. Demonstration of the functional significance of ultradian insulin oscillations.
; Scheen, André ; et al
in Journal of Clinical Investigation (1995), 95(4), 1464-71
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 ... [more ▼]
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. [less ▲]Detailed reference viewed: 20 (1 ULg)