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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 detailCrises financiere, economique, sociale, societale, morale, des reactions en chaine.
SCHEEN, André ULg

in Revue Médicale de Liège (2013), 68(1), 1-3

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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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See detailL’enzyme11β-HSD1 : une nouvelle cible potentielle pour le traitement du diabète de type 2 et des maladies métaboliques liées à l’obésité
SCHEEN, André ULg; BECK, Emmanuel ULg

in Diabète et Obésité (2013), 8

The 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) enzyme promotes the local conversion from cortisone to cortisol, especially in the adipose tissue and the liver. It may play a role in the ... [more ▼]

The 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) enzyme promotes the local conversion from cortisone to cortisol, especially in the adipose tissue and the liver. It may play a role in the pathophysiology of abdominal obesity and the metabolic syndrome, both showing some similarities with the Cushing syndrome. Synthetic selective inhibitors of 11βHSD1 are currently in development with encouraging preliminary results that remain, however, to be further improved. Selective inhibitors of 11βHSD1 may represent an innovative approach in the pharmacological management of obesity, metabolic syndrome and type 2 diabetes. [less ▲]

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See detailLa metformine: une molecule antidiabetique dotee de proprietes anti-cancereuses.
BECK, Emmanuel ULg; Scheen, André ULg

in Revue medicale de Liege (2013), 68(9), 444-9

Numerous epidemiological cohort and case-control studies showed that type 2 diabetes is a risk factor for cancer and that metformin therapy is associated with a significant reduction in the incidence of ... [more ▼]

Numerous epidemiological cohort and case-control studies showed that type 2 diabetes is a risk factor for cancer and that metformin therapy is associated with a significant reduction in the incidence of cancer and cancer-related death when compared to other glucose-lowering agents. Such beneficial effect is observed whatever the type of cancer, but seems to be more prominent in case of gastrointestinal and breast cancers. In general, the protective effect was more evident in observational cohort studies (however, more exposed to bias due to confounding factors) than in case-control studies. However, the results of the rather rare controlled clinical trials available are not conclusive, but none of them was performed with the objective to specifically assess cancer risk. Several meta-analyses recently confirmed that metformin therapy reduces the incidence of cancers (including colorectal cancer, hepatocarcinoma, breast cancer) and cancer-related mortality. Metformin may exert its anti-cancer activity by a direct effect (insulin) and an indirect effect (AMPK and mTOR). Considering all promising clinical information in patients with type 2 diabetes, further clinical trials are currently ongoing with the aim of assessing the role of metformin in oncology, especially as adjuvant in breast cancer therapy. [less ▲]

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See detailCardiovascular risk factors and complications associated with albuminuria and impaired renal function in insulin-treated diabetes.
Doggen, Kris; Nobels, Frank; SCHEEN, André ULg et al

in Journal of Diabetes & its Complications (2013)

AIMS: To establish the association between albuminuria and cardiovascular risk factors as well as micro- and macrovascular complications in type 1 and insulin-treated type 2 diabetes, both in the presence ... [more ▼]

AIMS: To establish the association between albuminuria and cardiovascular risk factors as well as micro- and macrovascular complications in type 1 and insulin-treated type 2 diabetes, both in the presence and in the absence of reduced estimated glomerular filtration rate (eGFR). METHODS: Cross-sectional study including 7640 insulin-treated diabetic patients (33% type 1) treated in specialist diabetes centers. Albuminuria was defined as >/=30mg/g, 20mg/L, 20mug/min or 30mg/24h. Reduced eGFR was defined as <60mL/min/1.73m2 (CKD-EPI equations). RESULTS: Albuminuria, reduced eGFR or a combination was more prevalent in type 2 (21.5%, 15.9% and 16.5%) than in type 1 diabetes (16.1%, 4.7% and 4.0%, all P<0.001 vs. type 2). Albuminuria was associated with poorer control of blood pressure, blood lipids and glycemia as well as higher prevalence of retinopathy and macrovascular disease, regardless of preserved/reduced eGFR or diabetes type. Reduced eGFR was associated with higher prevalence of micro- and macrovascular complications especially in type 2 diabetes. Combined presence of albuminuria and reduced eGFR was associated with the worst cardiovascular outcomes. CONCLUSIONS: Albuminuria and impaired renal function are prevalent in type 1 and insulin-treated type 2 diabetes. Albuminuria, but also normoalbuminuric renal impairment, is associated with micro- and macrovascular complications. [less ▲]

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See detailUtilisation de la metformine chez le patient diabetique cardiaque: balance benefices-risques.
Scheen, André ULg; Paquot, Nicolas ULg

in Revue medicale suisse (2013), 9(395), 1527-33

Metformin is unanimously considered as the first-line glucose-lowering agent in type 2 diabetes. Theoretically, however, it cannot be prescribed in a large proportion of patients because of the presence ... [more ▼]

Metformin is unanimously considered as the first-line glucose-lowering agent in type 2 diabetes. Theoretically, however, it cannot be prescribed in a large proportion of patients because of the presence of numerous contraindications corresponding to situations that may increase the risk of lactic acidosis. Recent data suggest that type 2 diabetes patients who are considered as being "at risk" because of the presence of cardiac disease still take benefit from metformin therapy, with a reduction of morbidity and mortality compared with other glucose-lowering agents. The present review analyzes the benefit-risk balance of metformin therapy in special populations, namely patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, or congestive heart failure. [less ▲]

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See detailComment concilier medecine factuelle et medecine personnalisee?
Scheen, André ULg

in Revue medicale suisse (2013), 9(395), 1499-500

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See detailJentadueto, combinaison fixe linagliptine- metformine pour le traitement du diabete de type 2.
Scheen, André ULg; Van Gaal, L. F.

in Revue medicale de Liege (2013), 68(9), 479-85

In case of failure of metformin monotherapy, several pharmacological strategies may be considered for the treatment of type 2 diabetes. Among these, the addition of an inhibitor of the dipeptidyl ... [more ▼]

In case of failure of metformin monotherapy, several pharmacological strategies may be considered for the treatment of type 2 diabetes. Among these, the addition of an inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme, a medication commonly named as gliptin, is increasingly used because of two main advantages over sulfonylureas, i.e. the absence of both hypoglycaemia and weight gain. The combination of a gliptin and metformin further improves glycaemic control compared to either monotherapy, due to complementary mechanisms of action. Most patients with type 2 diabetes are treated every day with numerous drugs because of the presence of comorbidities so that poor drug compliance is a major concern in such a population. The use of fixed-dose combinations (FDCs) may improve compliance and, therefore, several gliptin-metformin FDCs are now available. The most recent one is Jentadueto, which combines linagliptin, a selective DPP-4 inhibitor without renal excretion, and metformin, the first-line antidiabetic compound. This FDC is commercialized with two dosages of metformin, i.e. 2.5 mg linagliptin/850 mg metformin and 2.5 mg linagliptin/1.000 mg metformin, and should be administered twice daily with meal.While linagliptin may be prescribed whatever the renal function, the use of FDC should take into account classical restrictions imposed by the presence of metformin. [less ▲]

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See detailLa sitagliptine dans le traitement du diabete de type 2: le point, cinq ans apres sa commercialisation.
Scheen, André ULg; Van Gaal, L. F.

in Revue medicale de Liege (2013), 68(10), 504-10

Sitagliptin (Januvia) was the first selective inhibitor of dipeptidyl peptidase-4 commercialized for the management of type 2 diabetes. It is also available as a fixed-dose combination with meformin ... [more ▼]

Sitagliptin (Januvia) was the first selective inhibitor of dipeptidyl peptidase-4 commercialized for the management of type 2 diabetes. It is also available as a fixed-dose combination with meformin (Janumet). Almost 5 years after its launch in Belgium, the present review summarizes the most recent data regarding the clinical efficacy of this antidiabetic agent, the controversy about its safety profile, its use at lower dosage in case of moderate to severe renal insufficiency, the various indications that have been successively accepted and reimbursed, and, finally, the perspectives offered by a large ongoing cardiovascular outcome trial (TECOS). [less ▲]

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See detailLa vignette diagnostique de l'etudiant. L'anamnese medicale, etape initiale capitale pour l'orientation diagnostique.
Scheen, André ULg

in Revue medicale de Liege (2013), 68(11), 599-603

Medicine combines the characteristics of both a science and an art. The main objective is to cure the patient (or at least to alleviate symptoms). The first step of the global medical approach is to make ... [more ▼]

Medicine combines the characteristics of both a science and an art. The main objective is to cure the patient (or at least to alleviate symptoms). The first step of the global medical approach is to make a diagnosis, which will determine the therapy. Since Hippocrates, semiology, i.e. the study of both symptoms and signs, is crucial to make or guide the disease diagnosis. The development of more and more sophisticated medical technologies may lead to believe that semiology is not useful anymore in medical practice. It is absolutely not true because a careful semiology can provide precise diagnoses in a majority of cases or, at least, can lead to a limited differential diagnosis that helps in the selection of a few well defined complementary investigations. The aim of this article targeting mainly medical students is to emphasize the key rules of a well done medical interviewing, which should progress from an "analytical" approach to a "syndromic" approach, combining knowledge, know-how and self-management skills. [less ▲]

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