References of "Scheen, André"
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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 Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns.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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See detailUnsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages
L'Homme, Laurent ULg; Esser, Nathalie ULg; Riva, Laura ULg et al

in Journal of Lipid Research (2013), 54

The NLRP3 inflammasome is involved in many obesity-associated diseases such as type 2 diabetes, atherosclerosis and gouty arthritis through its ability to induce IL-1β release. The molecular link between ... [more ▼]

The NLRP3 inflammasome is involved in many obesity-associated diseases such as type 2 diabetes, atherosclerosis and gouty arthritis through its ability to induce IL-1β release. The molecular link between obesity and inflammasome activation is still unclear but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared to unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers including nigericin, alum and MSU. UFAs did not affect the transcriptional effect of SFAs suggesting a specific effect on the NLRP3 activation. These results provide a new antiinflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and therefore the IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases. [less ▲]

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See detailL’ALCOOLISME, UN MODÈLE D’ADDICTION AUX COMPLICATIONS SOMATIQUES MULTIPLES
PAQUOT, Nicolas ULg; DE FLINES, Jenny ULg; SCHEEN, André ULg

in Revue Médicale de Liège (2013), 68(5-6), 272-280

Alcoholism is, after smoking, the most common addiction in our society. It is associated with multiple familial, social and professional negative consequences. In addition, alcohol disturbs cellular ... [more ▼]

Alcoholism is, after smoking, the most common addiction in our society. It is associated with multiple familial, social and professional negative consequences. In addition, alcohol disturbs cellular metabolism and its excessive chronic consumption may lead to multiple dysfunctions that can provoke somatic complications targeting numerous tissues or organs. The present article describes the most important ones involving the liver, the digestive tract, the heart, both the central and peripheral nervous system, and bone marrow. We also discuss the metabolic disturbances associated with chronic alcohol consumption, among which those affecting glucose regulation, lipid profile, uric acid and various vitamins. Finally, we describe the nutritional deficiencies that may be observed in alcoholic people and may contribute to aggravate somatic complications. [less ▲]

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See detailDifférences d’activité de l’inflammasome NLRP3 entre sujets obèses avec et sans anomalies métaboliques
Esser, Nathalie ULg; L'Homme, Laurent ULg; DE ROOVER, Arnaud ULg et al

in Diabètes & Métabolism (2013, March), 39(suppl 1), 102

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See detailSGLT2 versus DPP4 inhibitors for type 2 diabetes.
Scheen, André ULg

in Lancet Diabetes & Endocrinology (2013), 1(3), 168-70

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See detailIssues in performing a network meta-analysis.
Senn, S; Gavini, F; Magrez, D et al

in Statistical Methods in Medical Research (2013), 22

The example of the analysis of a collection of trials in diabetes consisting of a sparsely connected network of 10 treatments is used to make some points about approaches to analysis. In particular ... [more ▼]

The example of the analysis of a collection of trials in diabetes consisting of a sparsely connected network of 10 treatments is used to make some points about approaches to analysis. In particular various graphical and tabular presentations, both of the network and of the results are provided and the connection to the literature of incomplete blocks is made. It is clear from this example that is inappropriate to treat the main effect of trial as random and the implications of this for analysis are discussed. It is also argued that the generalisation from a classic random-effect meta-analysis to one applied to a network usually involves strong assumptions about the variance components involved. Despite this, it is concluded that such an analysis can be a useful way of exploring a set of trials. [less ▲]

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See detailRecommandations europeennes pour la prise en charge du diabete, du pre-diabete et des maladies cardio-vasculaire. 1ere partie. Gestion du diabete et des facteurs de risque cardio-vasculaire.
Scheen, André ULg; RADERMECKER, Régis ULg; PHILIPS, Jean-Christophe ULg et al

in Revue medicale de Liege (2013), 68(11), 585-92

The patient with prediabetes or diabetes has a high or very high risk of cardiovascular diseases.We summarize the recent guidelines jointly published by the European Society of Cardiology and the European ... [more ▼]

The patient with prediabetes or diabetes has a high or very high risk of cardiovascular diseases.We summarize the recent guidelines jointly published by the European Society of Cardiology and the European Society for the Study of Diabetes. In this first article, we focus mainly on the preventive approaches of cardiovascular diseases in patients with prediabetes or (type 1 or type 2) diabetes. The crucial importance of a global multifactorial strategy is emphasized and the target levels of various risk factors are updated. The management of these cardiovascular complications in presence of diabetes will be considered in a second article. [less ▲]

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See detailPrise en charge du diabete gestationnel.
Philips, J. C.; EMONTS, Patrick ULg; Pintiaux, Axelle ULg et al

in Revue medicale de Liege (2013), 68(9), 489-96

Pregnancy is associated with relative carbohydrate intolerance and insulin resistance. Gestational diabetes mellitus (GDM) is recognized as a risk factor for a number of adverse outcomes during pregnancy ... [more ▼]

Pregnancy is associated with relative carbohydrate intolerance and insulin resistance. Gestational diabetes mellitus (GDM) is recognized as a risk factor for a number of adverse outcomes during pregnancy, including excessive fetal growth, increased incidence of birth trauma and neonatal metabolic abnormalities. This recognition has led to recommendations to screen all pregnant women for GDM and to treat those whose glucose tolerance tests exceed threshold criteria. Numerous epidemiological studies show that GDM affects between 1 and 25% of pregnancies, depending on the ethnicity of the population studied and the diagnostic criteria. Intervention to change lifestyle and, if maternal hyperglycemia persists, treatment with additional oral medication or insulin injections have shown to improve perinatal outcomes. Patients with GDM have a high risk of developing type 2 diabetes in the years after delivery and these women are encouraged to practice specific health behaviours (dietary habits, physical activity) during the postpartum period. The present article discusses the management of GDM in the light of data from the latest studies and international recommendations. [less ▲]

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