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See detailSquatting test: A posture to study and counteract cardiovascular abnormalities associated with autonomic dysfunction.
PHILIPS, Jean-Christophe ULg; SCHEEN, André ULg

in Autonomic neuroscience : basic & clinical (2011)

The squatting test is an active posture manoeuvre that imposes one of the most potent orthostatic stresses. In normal subjects, the changes in blood pressure and heart rate are transient because of ... [more ▼]

The squatting test is an active posture manoeuvre that imposes one of the most potent orthostatic stresses. In normal subjects, the changes in blood pressure and heart rate are transient because of appropriate baroreflex homeostasis and do not provoke symptoms. However, in various pathological conditions, both the increase in blood pressure during squatting and the decrease in blood pressure during standing may be more important and sustained, potentially leading to complaints and adverse events. Squatting has been used to evaluate patients with tetralogy of Fallot, heart transplant, dysautonomia, including diabetic cardiovascular autonomic neuropathy, and individuals prone to vasovagal syncope. Careful analysis of changes in blood pressure and heart rate during the transition from standing to squatting and from squatting to standing allows the early detection of altered vagal and/or sympathetic function. Of note squatting position has been proposed as a therapeutic means to counteract the fall in blood pressure in patients suffering from dizziness due to dysautonomia and orthostatic hypotension or presenting pre-syncope symptoms, such as soon after exercise. The aims of the present review are to analyse the haemodynamic pattern during a squatting test in various pathological situations and to describe what may be the negative and positive haemodynamic changes associated with this posture. We were especially interested in using the squatting test for the assessment of cardiovascular autonomic neuropathy associated with diabetes mellitus. [less ▲]

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See detailEtude de la pression artérielle, rigidité artérielle et neuropathie autonome cardiovasculaire chez les patients diabétiques de type 1
Philips, Jean-Christophe ULg; Xhignesse, Patricia ULg; Marchand, Monique ULg et al

in Vaisseaux, Coeur, Poumons (2010), 15(3), 70-73

Nous avons récemment eu l'honneur de recevoir l'Hypertension Young Investigator Award 2009 adressé par le Comité belge de Lutte contre l'Hypertension et soutenu par la fondation Astra Zeneca. Notre projet ... [more ▼]

Nous avons récemment eu l'honneur de recevoir l'Hypertension Young Investigator Award 2009 adressé par le Comité belge de Lutte contre l'Hypertension et soutenu par la fondation Astra Zeneca. Notre projet propose d'étudier différents indices cardiovasculaires au sein d'une population constituée de patients diabétiques de type 1. L'étude de la pression artérielle, estimée par différentes méthodes, ainsi que l'estimation de la rigidité artérielle chez ces patients pourraient être utiles afin d'apprécier le statut cardiovasculaire chez ces patients à haut risque. Notre service possède une certaine expérience dans la recherche et l'estimation de la neuropathie autonome cardiovasculaire (NAC) chez les patients diabétiques de type 1. Cette complication du diabète est associée à une morbi-mortalité d'origine cardiovasculaire accrue. Nous allons proposer une batterie de tests classiquement effectués dans le cadre de la recherche d'une NAC (en utilisant la technique du Finapress°). Ceux-ci seront combinés à d'autres explorations réalisées par nos confrères néphrologues (mesure ambulatoire de 24 heures de la pression artéielle ou MAPA et Sphygmocor°). Tous ces examens ont l'avantage d'être non-invasifs et peuvent être réalisés en routine clinique. Le recrutement de cette étude devrait permettre d'inclure une soixantaine de patients diabétiques de type 1 âgés de 20 à 50 ans et dont la durée de diabète varie entre 10 et 30 années. Cette population sera comparée à une cohorte de sujet sains apariés pour l'âge, l'indice de masse corporelle et le sexe. Plusieurs mesures sont effectuées et certains indices pourront être calculés après la réalisation des différents examens. Une comparaison entre les deux cohortes (diabétiques versus non-diabétiques) sera effectuée. L'évolution de certains paramètres au sein de la population diabétique sera aussi analysée (en fonction de l'âge et la durée du diabète par exemple). [less ▲]

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See detailEffect of sibutramine on cardiovascular outcomes in overweight and obese subjects.
James, W. P.; Caterson ID, I.D.; Coutinho, W. et al

in New England Journal of Medicine [=NEJM] (2010), 363

BACKGROUND: The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS: We ... [more ▼]

BACKGROUND: The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS: We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). RESULTS: The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. CONCLUSIONS: Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.) [less ▲]

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See detailSuspension de la commercialisation de la sibutramine et de la rosiglitazone en Europe
Scheen, André ULg

in Revue Médicale de Liège (2010), 65(10), 574-9

The European Medicines Agency (EMA) recommended the suspension of the marketing authorisations for sibutramine, a centrally-acting anti-obesity agent, and of rosiglitazone, an oral glucose-lowering ... [more ▼]

The European Medicines Agency (EMA) recommended the suspension of the marketing authorisations for sibutramine, a centrally-acting anti-obesity agent, and of rosiglitazone, an oral glucose-lowering compound of the thiazolidinedione family. This decision was taken because of a possible increased cardiovascular risk, mainly ischaemic heart disease, associated with the use of sibutramine or rosiglitazone in patients with pathologies prone to develop cardiovascular complications. The conclusion was that the benefits no longer outweigh the risks. The present paper summarizes the up- and -down history of these two pharmacological compounds, analyzes the data that resulted in such a decision and briefly discusses the future implications regarding the pharmacotherapy of cardiometabolic diseases. [less ▲]

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See detailL'etude clinique du mois. ACCORD-LIPID et ACCORD-EYE: vers un nouveau positionnement du fenofibrate chez le patient diabetique de type 2.
Scheen, André ULg; Van Gaal, L. F.

in Revue Médicale de Liège (2010), 65(9), 533-9

Fenofibrate has been evaluated in the ACCORD trial, in combination with a statin, to prevent vascular complications in patients with type 2 diabetes. In ACCORD-Lipid, the addition of fenofibrate was not ... [more ▼]

Fenofibrate has been evaluated in the ACCORD trial, in combination with a statin, to prevent vascular complications in patients with type 2 diabetes. In ACCORD-Lipid, the addition of fenofibrate was not able to significantly reduce the incidence of a composite cardiovascular endpoint (no positive effect was also observed with the intensification of blood glucose or blood pressure control in this population). However, an interaction effect was observed according to basal lipid profile, suggesting a better protection by fenofibrate in patients with hypertriglyceridaemia and low HDL cholesterol (so-called atherogenic dyslipidaemia). In ACCORD-Eye, the addition of fenofibrate to a basal statin therapy resulted in a significant reduction of the progression of diabetic retinopathy, in a similar manner as that observed with intensifying blood glucose control (but with a good safety profile and without increasing the risk of hypoglycaemia). These observations, confirming earlier results from FIELD also with this fibrate, open new perspectives for a useful prescription of fenofibrate in patients with type 2 diabetes. [less ▲]

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See detailManagement of blood glucose in patients with stroke.
Radermecker, Régis ULg; Scheen, André ULg

in Diabètes & Métabolism (2010), 36S3

Stroke is a leading cause of death worldwide and the most common cause of long-term disability amongst adults, more particularly in patients with diabetes mellitus and arterial hypertension. Increasing ... [more ▼]

Stroke is a leading cause of death worldwide and the most common cause of long-term disability amongst adults, more particularly in patients with diabetes mellitus and arterial hypertension. Increasing evidence suggests that disordered physiological variables following acute ischaemic stroke, especially hyperglycaemia, adversely affect outcomes. Post-stroke hyperglycaemia is common (up to 50% of patients) and may be rather prolonged, regardless of diabetes status. A substantial body of evidence has demonstrated that hyperglycaemia has a deleterious effect upon clinical and morphological stroke outcomes. Therefore, hyperglycaemia represents an attractive physiological target for acute stroke therapies. However, whether intensive glycaemic manipulation positively influences the fate of ischaemic tissue remains unknown. One major adverse event of management of hyperglycaemia with insulin (either glucose-potassium-insulin infusions or intensive insulin therapy) is the occurrence of hypoglycaemia, which can also induce cerebral damage. Novel insights into post-stroke hyperglycaemia management have been derived from continuous glucose monitoring systems (CGMS). This article aims: 1) to describe the adverse effects of hyperglycaemia following acute ischaemic stroke and the risk associated with iatrogenic hypoglycaemia; 2) to summarise the evidence from current glucose-lowering treatment trials; and 3) to show the usefulness of CGMS in both non-diabetic and diabetic patients with acute stroke. [less ▲]

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See detailContinuous glucose monitoring reduces both hypoglycaemia and HbA1c in hypoglycaemia-prone type 1 diabetic patients treated with a portable pump.
Radermecker, Régis ULg; Saint-Remy, Annie ULg; Scheen, André ULg et al

in Diabètes & Métabolism (2010), 36(5), 409-13

AIM: This study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and ... [more ▼]

AIM: This study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and presenting with frequent hypoglycaemic episodes. METHODS: Thirteen patients with type 1 diabetes (diabetes duration: 25+/-15 years; CSII duration: 5.5+/-7.0 years), with more than six recorded capillary blood glucose (CBG) values <60 mg/dL, according to their metres for the past 14 days, were offered the permanent use of a CGM device (Guardian RT((R)), Medtronic) plus ongoing self-monitoring of blood glucose (SMBG) for 12 weeks, followed by a 12-week crossover period of SMBG only, or vice versa. Glucose control, determined by recorded 14-day CBG values <60 mg/dL and HbA(1c) levels, and quality of life according to the Diabetes Quality of Life (DQOL) questionnaire, were assessed at baseline, and after 12- and 24-week follow-ups. RESULTS: Four patients withdrew from the study during the first period (of whom three were using CGM). In the nine study completers, the number of low CBG values decreased significantly from 13.9+/-9.2 to 7.6+/-6.8 (P=0.011) when patients used CGM, in either the initial or final trial period, while a decrease in HbA(1c) from 8.3+/-0.7 to 7.7+/-0.6% (P=0.049) was also observed, in contrast to the absence of any significant differences during the SMBG-only period. DQOL scores were also essentially unaffected. CONCLUSION: This pilot observational study supports the hypothesis that CGM use can significantly improve overall glucose control while reducing hypoglycaemic episodes in hypoglycaemia-prone type 1 diabetic patients treated by CSII. [less ▲]

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See detailMieux traiter le diabète : combattre l’inertie et améliorer l’adhésion au traitement.
SCHEEN, André ULg; PHILIPS, Jean-Christophe ULg; PAQUOT, Nicolas ULg

in Association belge du diabète (2010), 53

Le diabète est une maladie chronique par excellence. Comme beaucoup d’autres maladies chroniques, le diabète, qu’il soit de type 1 ou plus encore de type 2, est d’origine complexe, combinant l’infl uence ... [more ▼]

Le diabète est une maladie chronique par excellence. Comme beaucoup d’autres maladies chroniques, le diabète, qu’il soit de type 1 ou plus encore de type 2, est d’origine complexe, combinant l’infl uence de facteurs génétiques et environnementaux. Le but du traitement est de corriger au mieux l’hyperglycémie chronique, mais aussi d’autres facteurs de risque (hypertension artérielle, hypercholestérolémie,…), de façon à prévenir la survenue de complications, garantir une bonne qualité de vie et améliorer l’espérance de vie. [less ▲]

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See detailReduction du risque metabolique associe a l'obesite en modulant l'exposition tissulaire au cortisol.
Iovino, Alessandra ULg; Paquot, Nicolas ULg; Scheen, André ULg

in Revue Médicale Suisse (2010), 6(260), 1608-12

The 11-beta-hydroxysteroid dehydrogenase type 1 (11HSD1) enzyme promotes the local conversion from cortisone to cortisol, especially in the liver and the adipose tissue. It may play a role in the ... [more ▼]

The 11-beta-hydroxysteroid dehydrogenase type 1 (11HSD1) enzyme promotes the local conversion from cortisone to cortisol, especially in the liver and the adipose tissue. It may play a role in the pathophysiology of abdominal obesity and the metabolic syndrome, both showing some similarities with the Cushing syndrome. Considering experimental results obtained in rodents, the inhibition of this enzyme could exert favourable metabolic effects, with significant reductions in plasma glucose, insulin resistance and dyslipidaemia. Synthetic inhibitors of 11HSD1 are currently in development with encouraging preliminary results, first in animals, and more recently in humans. Selective inhibitors of 11HSD1 may represent an innovative approach in the pharmacological management of obesity, metabolic syndrome and type 2 diabetes in a near future. [less ▲]

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See detailApproche multirisque du patient diabetique de type 2: desaccord sur les valeurs cibles suite a l'etude ACCORD.
Scheen, André ULg; Paquot, Nicolas ULg

in Revue Médicale Suisse (2010), 6(260), 1582-7

The ACCORD trial investigated the effects of intensifying the global management of 10,251 type 2 diabetic patients, with established cardiovascular disease or at least two other cardiovascular risk ... [more ▼]

The ACCORD trial investigated the effects of intensifying the global management of 10,251 type 2 diabetic patients, with established cardiovascular disease or at least two other cardiovascular risk factors, on a composite endpoint (non fatal myocardial infarction, stroke and cardiovascular death). The attempt to reduce HbA1c level below 6% was associated with an increased cardiovascular mortality (despite a reduction in non fatal myocardial infarcts); lowering systolic blood pressure below 120 mmHg instead of 140 mmHg did not provide any additional benefit; finally, the control of atherogenic dyslipidaemia, with fenofibrate added to a statin, did not modify the composite endpoint (despite a positive effect in the subgroup of patients with high triglycerides and low HDL cholesterol). These rather disappointing results should be interpreted to provide practical guidelines. [less ▲]

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See detailL’hyperglycémie provoquée par voie orale (HGPO) revisitée 2e partie : Indices d’insulinosécrétion, d’insulinosensibilité et de disposition orale
SCHEEN, André ULg; LUYCKX, Françoise ULg

in Médecine des Maladies Métaboliques (2010), 4(6), 684-690

Oral glucose tolerance test (OGTT) has been widely used for the diagnosis of impaired glucose tolerance, diabetes mellitus and gestational diabetes. Simultaneous measurements of plasma glucose and insulin ... [more ▼]

Oral glucose tolerance test (OGTT) has been widely used for the diagnosis of impaired glucose tolerance, diabetes mellitus and gestational diabetes. Simultaneous measurements of plasma glucose and insulin (or more rarely C-peptide) levels allow to derive indices of insulin secretion and insulin sensitivity that are helpful for the understanding of disturbances in glucose metabolism and, especially, for the prediction of progression from normal glucose tolerance to impaired glucose tolerance or type 2 diabetes. Certain indices, quite simple, may be used in clinical practice (“insulinogenic index” to assess early insulin secretion, Matsuda index to assess insulin sensitivity) while others, more complex (and most often based on modelling procedures), are essentially used in research. The oral disposition index, a recently introduced marker that integrates insulin secretion and insulin sensitivity, raises increasing interest, more particularly for the prediction of type 2 diabetes. [less ▲]

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See detailCentral nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia.
Scheen, André ULg

in Diabètes & Métabolism (2010), 36S3

Recent evidence suggests that the brain has a key role in the control of energy metabolism, body fat content and glucose metabolism. Neuronal systems, which regulate energy intake, energy expenditure, and ... [more ▼]

Recent evidence suggests that the brain has a key role in the control of energy metabolism, body fat content and glucose metabolism. Neuronal systems, which regulate energy intake, energy expenditure, and endogenous glucose production, sense and respond to input from hormonal and nutrient-related signals that convey information regarding both body energy stores and current energy availability. In response to this input, adaptive changes occur that promote energy homeostasis and the maintenance of blood glucose levels in the normal range. Defects in this control system are implicated in the link between obesity and type 2 diabetes mellitus. The central nervous system may be considered the conductor of an orchestra involving many peripheral organs involved in these homeostatic processes. However, the brain is mainly a glucose-dependent organ, which can be damaged by both hypoglycaemia and hyperglycaemia. Hypoglycaemia unawareness is a major problem in clinical practice and is associated with an increased risk of coma. Stroke is another acute complication associated with diabetes mellitus, especially in elderly people, and the control of glucose level in this emergency situation remains challenging. The prognosis of stroke is worse in diabetic patients and both its prevention and management in at-risk patients should be improved. Finally, chronic diabetic encephalopathies, which may lead to cognitive dysfunction and even dementia, are also recognized. They may result from recurrent hypoglycaemia and/or from chronic hyperglycaemia leading to cerebral vascular damage. Functional imaging is of interest for exploring diabetes-associated cerebral abnormalities. Thus, the intimate relationship between the brain and diabetes is increasingly acknowledged in both research and clinical practice. [less ▲]

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See detailChanges in pulse pressure, heart rate and the pulse pressure x heart rate product during squatting in Type 1 diabetes according to age.
Philips, Jean-Christophe ULg; Marchand, Monique ULg; Scheen, André ULg

in Diabetic Medicine : A Journal of the British Diabetic Association (2010), 27(7), 753-61

AIMS: We assessed changes in pulse pressure and heart rate during a squatting test, as indirect markers of arterial stiffness and cardiovascular autonomic neuropathy, respectively, according to age and ... [more ▼]

AIMS: We assessed changes in pulse pressure and heart rate during a squatting test, as indirect markers of arterial stiffness and cardiovascular autonomic neuropathy, respectively, according to age and sex in patients with Type 1 diabetes mellitus. METHODS: We evaluated 160 diabetic patients, divided into four groups of 20 men and 20 women according to age (G1, 20-30 years old; G2, 31-40 years old; G3, 41-50 years old; and G4, 51-60 years old), and 160 non-diabetic matched control subjects. Each subject underwent a 3 min posture test (standing-squatting-standing) with continuous measurement of arterial blood pressure and heart rate by a Finapres device. Overall values throughout the test, baseline levels in initial standing position and squatting-induced changes in pulse pressure, heart rate and the pulse pressure x heart rate product were compared between diabetic patients and healthy control subjects. RESULTS: In the standing position, a greater increase in pulse pressure and lower reduction in heart rate with age led to a significantly higher pulse pressure x heart rate product in diabetic patients compared with control subjects. In the squatting position, a more marked pulse pressure increase in the absence of appropriate reduction in heart rate resulted in a greater rise in the pulse pressure x heart rate product in diabetic patients than in healthy subjects. No major differences were noted between the sexes, with the exception of a stronger relationship between pulse pressure and age in the female population with diabetes. Squatting-derived indices of cardiovascular autonomic neuropathy were also noted with increasing age in diabetic patients. CONCLUSIONS: The marked increase in the pulse pressure x heart rate product ('pulsatile stress') according to age, combined with cardiovascular autonomic neuropathy, may contribute to the higher cardiovascular risk of patients with Type 1 diabetes. [less ▲]

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See detailPulse pressure and pulsatile stress in overweight/obese patients versus lean subjects in absence of hypertension or diabetes.
Scheen, André ULg; Philips, Jean-Christophe ULg; Marchand, Monique ULg

in Obesity Reviews : An Official Journal of the International Association for the Study of Obesity (2010)

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See detailPulse pressure and pulsatile stress in overweight/obese nonhypertensive patients with versus without type 2 diabetes.
Scheen, André ULg; Philips, Jean-Christophe ULg; Marchand, Monique ULg

in Obesity Reviews : An Official Journal of the International Association for the Study of Obesity (2010)

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