References of "SCHEEN, André"
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See detailFactors associated with clinical inertia: an integrative review
Aujoulat, I; Jacquemin, p; Rietzschel, E et al

in Advances in Medical Education and Practice (2014), 5

Failure to initiate or intensify therapy according to evidence-based guidelines is increasingly being acknowledged as a phenomenon that contributes to inadequate management of chronic conditions, and is ... [more ▼]

Failure to initiate or intensify therapy according to evidence-based guidelines is increasingly being acknowledged as a phenomenon that contributes to inadequate management of chronic conditions, and is referred to as clinical inertia. However, the number and complexity of factors associated with the clinical reasoning that underlies the decision-making processes in medicine calls for a critical examination of the consistency of the concept. Indeed, in the absence of information on and justification of treatment decisions that were made, clinical inertia may be only apparent, and actually reflect good clinical practice. This integrative review seeks to address the factors generally associated with clinical inaction, in order to better delineate the concept of true clinical inertia. [less ▲]

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See detailMetabolically healthy overweight and obesity
Esser, Nathalie ULg; SCHEEN, André ULg; PAQUOT, Nicolas ULg

in Annals of Internal Medicine (2014), 160(7), 514

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See detailQu'apportent les nouvelles recommandations américaines à propos de la prise en charge des dyslipidémies en prévention cardiovasculaire ? Comparaison avec les recommandations européennes et belges
Descamps, O; Rietzschel, E; Langlois, M et al

in Louvain Medical (2014), 133(1), 26-35

Les dernières recommandations américaines concernant la prise en charge des dyslipidémies en prévention cardiovasculaire ont soulevé de nombreuses questions par leurs différences avec nos approches ... [more ▼]

Les dernières recommandations américaines concernant la prise en charge des dyslipidémies en prévention cardiovasculaire ont soulevé de nombreuses questions par leurs différences avec nos approches habituelles. Entre autres, elles ont éradiqué la nécessité de « cible » de LDL-C à atteindre en fonction du niveau de risque cardiovasculaire et ont proposé plutôt une stratégie basée sur l’intensité de la réduction relative du LDL-C. L’examen critique et la comparaison des recommandations font apparaitre, toutefois, plus de similitudes que de différences, tout en encourageant à repenser certains aspects de notre pratique et à raviver notre motivation pour le plus grand bien des patients. [less ▲]

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See detailInflammation as a link between obesity, metabolic syndrome and type 2 diabetes
ESSER, Nathalie ULg; Legrand, Sylvie ULg; Piette, Jacques ULg et al

in Diabetes Research & Clinical Practice (2014)

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic ... [more ▼]

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes. [less ▲]

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See detailLe temps de la reflexion... a propos de la demographie medicale et de la demographie "societale".
Scheen, André ULg

in Revue medicale de Liege (2014), 69(1), 1-3

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See detailLe medicament du mois. Le lixisenatide (Lyxumia): nouvel agoniste des recepteurs du glucagon-like peptide-1 a action preferentiellement post-prandiale.
Scheen, André ULg

in Revue medicale de Liege (2014), 69(2), 102-9

Lixisenatide (Lyxumia) is a new agonist of Glucagon-Like Peptide-1 (GLP-1) receptors that is indicated in the treatment of type 2 diabetes, in one single subcutaneous daily injection of 20 microg. It ... [more ▼]

Lixisenatide (Lyxumia) is a new agonist of Glucagon-Like Peptide-1 (GLP-1) receptors that is indicated in the treatment of type 2 diabetes, in one single subcutaneous daily injection of 20 microg. It exerts an incretin effect by stimulating insulin secretion after a meal while inhibiting glucagon secretion, both in a glucose-dependent manner, which limits the risk of hypoglycaemia. In addition, it slows down gastric emptying after a meal, which contributes to reduce postprandial hyperglycaemia, especially after breakfast. Lixisenatide is currently reimbursed in Belgium after failure of a dual therapy with metformin and a sulfonylurea but also in combination with a basal insulin (with or without oral antidiabetic drugs). The latter interesting combination should tackle fasting glycaemia with basal insulin (after appropriate dose titration) and postprandial hyperglycaemia with the GLP-1 receptor agonist in a complementary manner. The consequence is a further improvement of glycated haemoglobin (HbA(1c)) varying between 0.3 and 0.9% in various studies comparing lixisenatide versus placebo. As other compounds of the class, lixisenatide induces a small weight reduction, which contrasts with the weight gain commonly observed with other antidiabetic medications (including insulin). Further studies should demonstrate the effects of lixisenatide on vascular complications and overall prognosis of patients with type 2 diabetes. [less ▲]

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See detailLa vignette diagnostique de l'etudiant. Diagnostic et evaluation d'une hypoglycemie chez le patient diabetique.
Scheen, André ULg

in Revue medicale de Liege (2014), 69(2), 110-5

Hypoglycaemic episodes are rather common among diabetic patients, especially those treated with sulfonylureas or insulin (more in type 1 than in type 2 diabetes). The presentation of hypoglycaemia may ... [more ▼]

Hypoglycaemic episodes are rather common among diabetic patients, especially those treated with sulfonylureas or insulin (more in type 1 than in type 2 diabetes). The presentation of hypoglycaemia may considerably vary from patient-to-patient and from time-to-time in a given patient. With the illustration of a clinical case, we will describe the characteristics of the three main types of hypoglycaemia: severe hypoglycaemia (with or without coma), symptomatic hypoglycaemia (with or without confirmation) and asymptomatic hypoglycaemia ("hypoglycaemia unawareness") discovered as a low blood glucose measurement. We will also briefly analyse the reasons of such differences and the potential clinical consequences that these three main types of hypoglycaemia may exert in the real life of diabetic patients. [less ▲]

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See detailEffects of glucose-lowering agents on vascular outcomes in type 2 diabetes: A critical reappraisal.
Scheen, André ULg; Charbonnel, B.

in Diabetes & metabolism (2014)

Type 2 diabetes mellitus (T2DM) is strongly associated with cardiovascular complications, especially coronary artery disease. Numerous epidemiological studies have shown a close relationship between major ... [more ▼]

Type 2 diabetes mellitus (T2DM) is strongly associated with cardiovascular complications, especially coronary artery disease. Numerous epidemiological studies have shown a close relationship between major cardiovascular events and glycaemia, and several pathophysiological mechanisms have been described that explain how hyperglycaemia induces vascular damage. However, randomized controlled trials investigating either an intensive glucose-lowering strategy vs standard care or the addition of a new glucose-lowering agent vs a placebo have largely failed to demonstrate any clinical benefits in terms of cardiovascular morbidity or mortality. This lack of evidence has led some people to contest the clinical efficacy of lowering blood glucose in patients with T2DM, despite its positive effects on microvascular complications. This article analyzes the various reasons that might explain such discrepancies. There are still strong arguments in favour of targeting hyperglycaemia while avoiding other counterproductive effects, such as hypoglycaemia and weight gain, and of integrating the glucose-lowering approach within a global multi-risk strategy to reduce the burden of cardiovascular disease in T2DM. [less ▲]

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See detailPharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease.
Scheen, André ULg

in Expert opinion on drug metabolism & toxicology (2014)

Introduction: Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients ... [more ▼]

Introduction: Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents may be a cause for concern in the case of hepatic impairment (HI). Areas covered: An extensive literature search was performed to analyze the influence of HI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice as far as the efficacy/safety balance of their use in diabetic patients with CLD is concerned. Expert opinion: Almost no PK studies have been published regarding metformin, sulfonylureas, thiazolidinediones and alpha-glucosidase inhibitors in patients with HI. Only mild changes in PK of glinides, dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporters type 2 inhibitors were observed in dedicated PK studies in patients with various degrees of HI, presumably without major clinical relevance although large clinical experience is lacking. Glucagon-like peptide-1 receptor agonists have a renal excretion rather than liver metabolism. Rare anecdotal case reports of hepatotoxicity have been described with various glucose-lowering agents contrasting with numerous reassuring data. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, including with the use of metformin. [less ▲]

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See detailPersonalising metformin therapy: a clinician's perspective
SCHEEN, André ULg

in Lancet Diabetes & Endocrinology (2014)

If lifestyle changes are not effective for maintaining glycaemic control, metformin is recommended as the first glucose-lowering drug to use in a patient with type 2 diabetes, if the patient has no ... [more ▼]

If lifestyle changes are not effective for maintaining glycaemic control, metformin is recommended as the first glucose-lowering drug to use in a patient with type 2 diabetes, if the patient has no contraindications—eg, renal impairment or hypoxic disorders.1 However, the glucose-lowering response to metformin can vary greatly between patients, with some people responding poorly to this biguanide. Because of the well known therapeutic inertia with respect to pharmacological treatment of diabetes, insufficient glucose control might persist for a long time before any treatment adjustment is made in people who respond poorly to metformin monotherapy. [less ▲]

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See detailCombating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes
SCHEEN, André ULg; Van Gaal, Luc

in The Lancet Diabetes & Endocrinology (2014)

The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent ... [more ▼]

The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine–controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes. [less ▲]

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See detailPharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor.
Scheen, André ULg

in Clinical pharmacokinetics (2014), 53(3), 213-25

Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes ... [more ▼]

Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors, including empagliflozin, are the first pharmacological class of antidiabetes agents to target the kidney in order to remove excess glucose from the body and, thus, offer new options for T2DM management. SGLT2 inhibitors exert their effects independently of insulin. Following single and multiple oral doses (0.5-800 mg), empagliflozin was rapidly absorbed and reached peak plasma concentrations after approximately 1.33-3.0 h, before showing a biphasic decline. The mean terminal half-life ranged from 5.6 to 13.1 h in single rising-dose studies, and from 10.3 to 18.8 h in multiple-dose studies. Following multiple oral doses, increases in exposure were dose-proportional and trough concentrations remained constant after day 6, indicating a steady state had been reached. Oral clearance at steady state was similar to corresponding single-dose values, suggesting linear pharmacokinetics with respect to time. No clinically relevant alterations in pharmacokinetics were observed in mild to severe hepatic impairment, or in mild to severe renal impairment and end-stage renal disease. Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin. Urinary glucose excretion (UGE) rates were higher with empagliflozin versus placebo and increased with dose, but no relevant impact on 24-h urine volume was observed. Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations. [less ▲]

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See detailDrug-Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus.
Scheen, André ULg

in Clinical pharmacokinetics (2014)

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel ... [more ▼]

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (C max) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment. [less ▲]

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See detailEvaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations.
Scheen, André ULg

in Expert opinion on drug metabolism & toxicology (2014)

Introduction: Inhibitors of sodium-glucose cotransporters type 2 (SGLT2), which increase urinary glucose excretion independently of insulin, are proposed as a novel approach for the management of type 2 ... [more ▼]

Introduction: Inhibitors of sodium-glucose cotransporters type 2 (SGLT2), which increase urinary glucose excretion independently of insulin, are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Areas covered: An extensive literature search was performed to analyze the pharmacokinetic characteristics, toxicological issues and safety concerns of SGLT2 inhibitors in humans. This review focuses on three compounds (dapagliflozin, canagliflozin, empagliflozin) with results obtained in healthy volunteers (including drug-drug interactions), patients with T2DM (single dose and multiple doses) and special populations (those with renal or hepatic impairment). Expert opinion: The three pharmacological agents share an excellent oral bioavailability, long half-life allowing once-daily administration, low accumulation index and renal clearance, the absence of active metabolites and a limited propensity to drug-drug interactions. No clinically relevant changes in pharmacokinetic parameters were observed in T2DM patients or in patients with mild/moderate renal or hepatic impairment. Adverse events are a slightly increased incidence of mycotic genital and rare benign urinary infections. SGLT2 inhibitors have the potential to reduce several cardiovascular risk factors, and cardiovascular outcome trials are currently ongoing. The best positioning of SGLT2 inhibitors in the armamentarium for treating T2DM is still a matter of debate. [less ▲]

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See detailRECOMMANDATIONS EUROPÉENNES POUR LA PRISE EN CHARGE DU DIABÈTE, DU PRÉ-DIABÈTE ET DES MALADIES CARDIO-VASCULAIRES 2ème partie. Gestion des complications cardiaques, cérébro-vasculaires et artériopathiques périphériques
SCHEEN, André ULg; LANCELLOTTI, Patrizio ULg

in Revue Médicale de Liège (2013), 68(12), 617-624

Summary : Patients with prediabetes (dysglycaemia) or diabetes present accelerated atherosclerosis that predisposes them to multiple cardiovascular complications. We summarize here the joint ... [more ▼]

Summary : Patients with prediabetes (dysglycaemia) or diabetes present accelerated atherosclerosis that predisposes them to multiple cardiovascular complications. We summarize here the joint recommendations recently published by the European Society of Cardiology and the European Society for the Study of Diabetes. The management of main risk factors, aiming to optimize primary or secondary prevention, has been developed in a first article. This second article is focusing on the management of cardiac, cerebrovascular and peripheral arteriopathic complications. The importance of an individualized patient-centered strategy is emphasized, including the management of microangiopathies and, ideally, within a multidisciplinary approach. [less ▲]

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See detailObesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue
ESSER, Nathalie ULg; L'Homme, Laurent ULg; DE ROOVER, Arnaud ULg et al

in Diabetologia (2013), 56

Aims/hypothesis Obesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose ... [more ▼]

Aims/hypothesis Obesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose tissue is also heterogeneous in that its visceral component is more frequently associated with metabolic dysfunction than its subcutaneous component. The development of metabolic disorders is partly mediated by the NLR family pyrin domain containing-3 (NLRP3) inflammasome, which increases the secretion of inflammatory cytokines via activation of caspase-1. We compared the immunological profile and NLRP3 activity in adipose tissue between MUO and MHO individuals. Methods MHO and MUO phenotypes were defined, respectively, as the absence and the presence of the metabolic syndrome. Cellular composition and intrinsic inflammasome activity were investigated by flow cytometry, quantitative RTPCR and tissue culture studies in subcutaneous and visceral adipose tissue from 23 MUO, 21 MHO and nine lean individuals. Results We found significant differences between the three study groups, including an increased secretion of IL-1β, increased expression of IL1B and NLRP3, increased number of adipose tissue macrophages and decreased number of regulatory T cells in the visceral adipose tissue of MUO patients compared with MHO and lean participants. In macrophages derived from visceral adipose tissue, both caspase-1 activity and IL-1β levels were higher in MUO patients than in MHO patients. Furthermore, caspase-1 activity was higher in CD11c+CD206+ adipose tissue macrophages than in CD11c−CD206+ cells. Conclusions/interpretation The MUO phenotype seems to be associated with an increased activation of the NLPR3 inflammasome in macrophages infiltrating visceral adipose tissue, and a less favourable inflammatory profile compared with the MHO phenotype. [less ▲]

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