Exhaustion of blood glucose response and enhancement of insulin response after repeated glucagon injections in type-2 diabetes: potentiation by progressive hyperglycemia.
; Scheen, André ; et al
in Annales d'Endocrinologie (1996), 57(5), 395-402
AIMS: To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS: In overnight fasted Type-2 diabetic patients ... [more ▼]
AIMS: To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS: In overnight fasted Type-2 diabetic patients, three i.v. glucagon (1 mg) injections were given as a bolus at two-hour intervals. In the hour preceding each glucagon injection, 6 patients received saline and they were tested at near-baseline blood glucose levels, while 8 patients received a glucose-controlled glucose infusion and they were tested at increasing blood glucose levels (7.5 +/- 0.2, 12.9 +/- 0.5 and 18.7 +/- 0.7 mmol/l). Blood samples were collected at 0, 3, 5, 10, 15, 30 and 60 min after each glucagon injection. RESULTS: In the patients tested at near-baseline blood glucose levels, the blood glucose rise induced by glucagon was smaller after repeated injections. By contrast, the B-cell response to glucagon was well preserved. In the patients tested at increasing blood glucose levels, the blood glucose response to glucagon was abolished after repeated injections. By contrast, the B-cell response was significantly potentiated. The respective areas under the curve of plasma insulin levels in response to glucagon were 563 +/- 72, 1047 +/- 154 and 1844 +/- 305 m U x 30 min/l (p < 0.001). CONCLUSION: In Type-2 (non-insulin-dependent) diabetic patients, repeated glucagon injections, even when administered in a short (4 h) period of time, do not exhaust the B-cell. Endogenous insulin secretion is even potentiated at increasing blood glucose levels. By contrast, the hyperglycemic response to glucagon is significantly abolished, particularly at high blood glucose levels. [less ▲]Detailed reference viewed: 13 (0 ULg)
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)
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: 30 (1 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: 68 (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: 32 (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: 79 (0 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: 46 (2 ULg)
Glucose handling, diabetes and ageing.
; Scheen, André ; Lefebvre, Pierre
in Hormone Research (1995), 43(1-3), 52-7
The relationship between ageing and glucose homeostasis is still an open debate. In fact, the mechanisms by which glucose metabolism is progressively impaired with increasing age are not completely ... [more ▼]
The relationship between ageing and glucose homeostasis is still an open debate. In fact, the mechanisms by which glucose metabolism is progressively impaired with increasing age are not completely understood. In the present report we have reviewed the possible mechanisms (impaired insulin secretion and action, role of the environmental factors) which may lead to the impairment in glucose handling associated with ageing. We also point out that not all aged subjects are glucose intolerant; in fact, it has been suggested that only those aged subjects who present more than one pathological finding do in fact develop impaired glucose handling. [less ▲]Detailed reference viewed: 16 (1 ULg)
Vieillissement, défenses immunitaires at axe somatotrope-facteurs de croissance apparentés à l'insuline
Kaiser, Marie-Joëlle ; ; et al
in Médecine et Hygiène (1995), 53Detailed reference viewed: 73 (3 ULg)
Cellular and molecular aspects of thymic T-cell education to neurohypophysial peptides
Geenen, Vincent ; ; Martens, Henri et al
in Yoshida, Sho; Saito, Toshikazu; Kurokawa, Kiyoshi (Eds.) Neurohypophysis - Recent Progress of Vasopressin and Oxytocin Research (1995)
Our studies have shown that oxytocin (OT) is the dominant peptide of the neurohypophysial (NHP) family that is expressed by thymic epithelial/nurse cells (TEC/TNC). Both in specific RIA and ICC analyses ... [more ▼]
Our studies have shown that oxytocin (OT) is the dominant peptide of the neurohypophysial (NHP) family that is expressed by thymic epithelial/nurse cells (TEC/TNC). Both in specific RIA and ICC analyses, vasopressin (VP) immunoreactivity is considerably lower in TEC. OT is not secreted by TEC/TNC, but it is presented as the self antigen of the NHP family to developing pre-T cells. The process of T-cell education in recognizing the NHP family involves an active cooperation between this neuroendocrine gene/protein family and the immunoglobulin family. This cooperation is illustrated by the identification in plasma membranes of human TEC of a 55-kDa protein bearing a neurophysin (10 kDa), as well as a MHC class I heavy chain-related domain (45 kDa). Since both OT and VP genes are transcribed in the thymus, the site of this cooperation should be located at posttranscriptional level. From these data, it appears that thymic T-cell education to the NHP family involves specific pathways which are not strictly superimposible to those dlineated using peripheral dedicated APC. Although MHC class I pathways are needed, it appears that thymic T-cell education to NHP self is not restricted in an allelic fashion. This offers significant advantages for the selection of the human T-cell repertoire. Furthermore, the absence of a tight MHC allelic restriction in the process of T-cell education to neuroendocrine self opens novel perpectives for the prevention of autoimmune endocrine disorders such as insulin-dependent diabetes mellitus. [less ▲]Detailed reference viewed: 30 (2 ULg)
Cryptocrine Signaling in the Thymus Network and T Cell Education to Neuroendocrine Self-Antigens
Geenen, Vincent ; ; Martens, Henri et al
in Journal of Molecular Medicine : Official Organ of the 'Gesellschaft Deutscher Naturforscher und Ärzte' (1995), 73(9), 449-55
Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental ... [more ▼]
Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes. [less ▲]Detailed reference viewed: 23 (7 ULg)
Amylin/islet amyloid polypeptide: biochemistry, physiology, patho-physiology.
; Scheen, André ; Lefebvre, Pierre
in Diabète & Métabolisme (1995), 21(1), 3-25
Amylin is a 37 amino-acid peptide mainly produced by the islet beta-cell. Aggregation of amylin is partly responsible for amyloid formation. Amyloid deposits occur both extracellularly and intracellularly ... [more ▼]
Amylin is a 37 amino-acid peptide mainly produced by the islet beta-cell. Aggregation of amylin is partly responsible for amyloid formation. Amyloid deposits occur both extracellularly and intracellularly and may contribute to beta-cell degeneration. Amylin is packed in beta-cell granules and cosecreted with insulin in response to the same stimuli but, unlike other beta-cell products, it is produced from specific a gene on chromosome 12. Basal, plasma amylin concentrations are around 5 pM, and increase fourfold after meals or glucose. Higher levels are found in cases of insulin resistance, obesity, gestational diabetes and in some patients with NIDDM. Low or absent levels are found in insulin-dependent diabetic patients. There are similarities between amylin and non beta-cell peptides such as calcitonin gene related peptides (CGRP). They may bind to the same receptor, determine similar post-receptor phenomena and qualitatively similar actions but with different degree of potency. The actions of amylin are multiple and mostly exerted in the regulation of fuel metabolism. In muscle, amylin opposes glycogen synthesis, activates glycogenolysis and glycolysis (increasing lactate production). Consequently, amylin increases lactate output by muscle and increases the plasma lactate concentration. In fasting conditions, this lactate may serve as a gluconeogenic substrate for the liver, contributing to replenish depleted glycogen stores and to increase glucose production. In non-fasting conditions, lactate can be transformed by liver in triglycerides. It is not clear at present whether amylin actions on the liver are direct or mediated by changes in circulating metabolites. A probably indirect effect of amylin in muscle is to decrease insulin- (or glucose)-induced glucose uptake, which may contribute to insulin resistance. Other actions include inhibition of glucose-stimulated insulin secretion and, in general, actions mimicking CGRP effects. Some of these actions are seen at supraphysiological concentrations. The physiopathological consequences of amylin deficiency, or excess are under active by investigated. [less ▲]Detailed reference viewed: 42 (1 ULg)
Retinopathy, but not neuropathy, is influenced by the level of residual endogenous insulin secretion in type 2 diabetes.
Bozet, Marie-Claire ; Scheen, André ; Gerard, Pascale et al
in Diabète & Métabolisme (1995), 21(5), 353-9
The files of 132 patients with Type 2 diabetes were retrospectively studied to characterize the influence of metabolic control and residual insulin secretion on neuropathy and retinopathy, the two most ... [more ▼]
The files of 132 patients with Type 2 diabetes were retrospectively studied to characterize the influence of metabolic control and residual insulin secretion on neuropathy and retinopathy, the two most frequent degenerative diabetic complications. Patients were classified according to their metabolic control (mean HbA1C either < or > or = 8%; reference values: 3-6%) and residual endogenous insulin secretion (fasting plasma C-peptide levels either < or > or = 0.600 nmol/l). Neuropathy was more frequent in patients with poor metabolic control (32/64 = 50%) than in those adequately controlled (17/68 = 25%; p < 0.005). In both subgroups, the level of endogenous insulin secretion did not influence the prevalence of neuropathy. Retinopathy was less effected than neuropathy by the degree of metabolic control (37.5% in the subgroup with HbA1C > or = 8% v.s. 25% in the subgroup with HbA1C < 8%; p < 0.10), but was influenced by residual insulin secretion. Indeed, in patients with inadequate metabolic control, the prevalence of retinopathy was significantly increased in those with higher endogenous insulin secretion (51.4 versus 20.6%, p < 0.02) and thus probably higher insulin resistance. Furthermore, higher systolic arterial blood pressure was observed in the subgroups with a higher prevalence of retinopathy. Such conclusions were confirmed using multivariate analysis. Thus, in Type 2 diabetes, neuropathy is essentially affected by the degree of metabolic control, whereas retinopathy is also influenced by the level of residual endogenous insulin secretion and the presence of systolic hypertension. [less ▲]Detailed reference viewed: 10 (0 ULg)
Antihyperglycaemic agents. Drug interactions of clinical importance.
Scheen, André ; Lefebvre, Pierre
in Drug Safety : An International Journal of Medical Toxicology & Drug Experience (1995), 12(1), 32-45
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 ... [more ▼]
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. [less ▲]Detailed reference viewed: 39 (0 ULg)
Postgastroplasty recovery of ideal body weight normalizes glucose and insulin metabolism in obese women.
Letiexhe, Michel ; Scheen, André ; Gerard, Pascale et al
in Journal of Clinical Endocrinology and Metabolism (1995), 80(2), 364-9
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 ... [more ▼]
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. [less ▲]Detailed reference viewed: 18 (1 ULg)
Modified glucagon test allowing simultaneous estimation of insulin secretion and insulin sensitivity: application to obesity, insulin-dependent diabetes mellitus, and noninsulin-dependent diabetes mellitus.
; Scheen, André ; Lefebvre, Pierre
in Journal of Clinical Endocrinology and Metabolism (1995), 80(2), 393-9
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 ... [more ▼]
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. [less ▲]Detailed reference viewed: 64 (0 ULg)
Improving the action of insulin.
Lefebvre, Pierre ; Scheen, André
in Clinical & Investigative Medicine = Médecine Clinique et Experimentale (1995), 18(4), 340-7
Improving the action of insulin is a relatively new concept in diabetes management. Insulin sensitivity can be improved by reduction of excessive body weight, regular physical activity and, possibly, by ... [more ▼]
Improving the action of insulin is a relatively new concept in diabetes management. Insulin sensitivity can be improved by reduction of excessive body weight, regular physical activity and, possibly, by correcting a subclinical magnesium deficiency. Pharmacological means of improving insulin action include metformin, antiobesity serotoninergic agents and, possibly, benfluorex. New compounds aiming at improving the action of insulin are in development and include thiazolidinedione derivatives (known as "insulin sensitizers"), inhibitors of adipose tissue lipolysis (e.g. acipimox), and inhibitors of free fatty acid oxidation (e.g. etomoxir). Avoidance of drugs that reduce insulin sensitivity, such as beta blockers and thiazide diuretics, is recommended. Finally, cigarette smoking is associated with resistance to insulin but it remains to be demonstrated that cessation of cigarette smoking does in fact increase sensitivity to insulin. [less ▲]Detailed reference viewed: 11 (0 ULg)
Short administration of metformin improves insulin sensitivity in android obese subjects with impaired glucose tolerance.
Scheen, André ; Letiexhe, Michel ; Lefebvre, Pierre
in Diabetic Medicine : A Journal of the British Diabetic Association (1995), 12(11), 985-9
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 ... [more ▼]
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. [less ▲]Detailed reference viewed: 25 (1 ULg)