Discrepancies between the Cockcroft–Gault and Chronic Kidney Disease Epidemiology (CKD-EPI) Equations: Implications for Refining Drug Dosage Adjustment Strategies
DELANAYE, Pierre ; ; SCHEEN, André et al
in Clinical Pharmacokinetics (in press)Detailed reference viewed: 40 (3 ULg)
Etude transfrontalière des besoins de formation en Education Thérapeutique du Patient souffrant de diabète et/ou d’obésité pour le personnel médical et paramédical : enquête par méthode du groupe nominal
Pétré, Benoît ; Ketterer, Frédéric ; Vanmeerbeek, Marc et al
in Presse Médicale (2016), 45(10), 351-361
INTRODUCTION: The design of continuous training programs in therapeutic patient education (ETP) should be inspired by needs shown by the professionals concerned in terms of mobilization or acquisition of ... [more ▼]
INTRODUCTION: The design of continuous training programs in therapeutic patient education (ETP) should be inspired by needs shown by the professionals concerned in terms of mobilization or acquisition of skills in this domain. The objective of this study is to analyze needs expressed by healthcare professionals (HP) involved in patients' management presenting a type 2 diabetes (T2D) and/or obesity and to compare them with the existing recommendations. METHODS: One hundred and five PS (general practitioners, dietitians and nurses) of 3 frontier regions of French-speaking European countries (France, Belgium and Grand duchy of Luxembourg) were questioned in 12 monodisciplinary groups according to the technique of the nominal group. Needs expressed by the participants were classified in the categories of the reference table of skills to dispense TPE (National Institute for Health Prevention and Education [INPES], 2013). RESULTS/DISCUSSION: Among needs expressed by HP, 52 % of the votes targeted relational skills, 10 % of the skills relative to the biomedical techniques, 20 % of the skills relative to the educational techniques and 11 %, those of organization and the coordination. Seven percent of the proposals were out of the categories of the INPES. Results do not allow to establish profiles of skills according to the studied region or profession. The recognition of the TPE by the French legislation does not seem to influence in a major way the data. CONCLUSION: The needs expressed by PS in the context of this study are focused on the relation HP/patient that is the heart of the TPE. It would however be necessary to raise awareness among HP in the acquisition of the other skills which concern in particular the animation of group, the interprofessional coordination, the consideration of the environment or more generally the procedures. [less ▲]Detailed reference viewed: 181 (58 ULg)
The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club.
Cavalier, Etienne ; ; Bruyère, Olivier et al
in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA (2016), 27
The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state ... [more ▼]
The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis. [less ▲]Detailed reference viewed: 31 (4 ULg)
Relations entre neuropathie autonome cardiaque (NAC), pression pulsée (PP) et insuffisance rénale chronique (IRC) chez le patient diabétique de type 2 (DT2)
PHILIPS, Jean-Christophe ; MARCHAND, Monique ; SCHEEN, André
Poster (2016, March)
Objectifs : Ce travail étudie les relations entre trois complications diabétiques, la NAC, l’élévation de PP (marqueur de rigidité artérielle) et la diminution du débit de filtration glomérulaire (DFG ... [more ▼]
Objectifs : Ce travail étudie les relations entre trois complications diabétiques, la NAC, l’élévation de PP (marqueur de rigidité artérielle) et la diminution du débit de filtration glomérulaire (DFG) chez le patient DT2. Patients et méthodes : L’étude comprend 79 patients DT2 (53H/26F; 56±8 années; 11±8 années de DT2; IMC 28,4±4,6 kg/m²) analysés par enregistrement continu de la pression artérielle (PA) et de la fréquence cardiaque (appareil Finapres) lors d’un test postural standardisé. Le gain baro-réflexe (GBR, indice de NAC) correspond à la pente de la relation entre les espaces R-R et PA systolique (PAS) lors du redressement accroupi-debout. PP est analysée pendant tout le test et par son augmentation durant l’accroupissement (delta PP). DFG est estimé par la formule MDRD au début puis après un suivi moyen de 12±5 ans. Résultats : Les valeurs initiales sont : HbA1c : 8,8± 1,7%; DFG : 86±25 ml/min ; PP : 62±10 mmHg; BRG : 1,8±1,4 msec/mmHg. DFG est inversement corrélé à l’âge (r=-0,317; p=0,020), très positivement corrélé avec GBR (r=0,453; p=0,008), sans corrélation significative avec HbA1c (r=-0,023; p=0,935) ni avec PAS, PP ou encore delta PP (r=-0,206; p=0,114; NS). La diminution de DFG (-12±23 ml/min) lors du suivi de 12 ans n’a pu être corrélée de façon significative aux valeurs initiales et finales d’HbA1c, ni aux valeurs initiales de GBR (et d’autres marqueurs de NAC) ou de PA, même si la relation est proche de la signification pour delta PP (r=0,20; p=0,060). Conclusion : La forte relation initiale entre DFG et GBR suggère que IRC et NAC sont aggravées de façon conjointe et, possiblement, qu’une des deux complications influence l’autre. L’absence de toute corrélation entre la chute ultérieure de DFG et les autres paramètres initiaux peut s’expliquer par l’origine multifactorielle de la progression de l’IRC chez le patient DT2. [less ▲]Detailed reference viewed: 36 (2 ULg)
Antihyperglycémiants, antihypertenseurs et hypolipidémiants : comparaison des effets sur la mortalité et la morbidité cardiovasculaire chez le patient diabétique de type 2
Poster (2016, March)
Introduction : Réduire le risque de mortalité et morbidité cardiovasculaire (CV) chez le patient diabétique de type 2 (DT2) est primordial, mais les effets protecteurs semblent différents selon le mode ... [more ▼]
Introduction : Réduire le risque de mortalité et morbidité cardiovasculaire (CV) chez le patient diabétique de type 2 (DT2) est primordial, mais les effets protecteurs semblent différents selon le mode d’intervention pharmacologique étudié. Patients et méthodes : Les données de mortalité (totale et CV) et morbidité (infarctus du myocarde ou IDM, accidents vasculaires cérébraux ou AVC) rapportées (réduction du risque relatif) dans les essais ayant testé un traitement anti-hyperglycémiant sont comparées avec les résultats publiés dans deux méta-analyses concernant les hypolipidémiants et les anti-hypertenseurs consacrées au DT2. Résultats : Les antihypertenseurs réduisent les IDM (-12%) et la mortalité globale (-13%) de façon comparable, et diminuent davantage les AVC (-27%). Les hypolipidémiants diminuent davantage les IDM (- 22%) et les AVC (-21%) que la mortalité globale (-9%) (ou la mortalité CV : - 13%). Les données concernant les antihyperglycémiants diffèrent considérablement selon les médications testées. L’insuline et les sulfamides (UKPDS) réduisent plus les IDM (- 21%) que la mortalité totale (-8%), mais augmentent les AVC (+ 14%). La metformine (UKPDS) réduit, de façon comparable, les IDM (-39%), les AVC (-41%) et la mortalité totale (-36%). La pioglitazone (PROactive) diminue davantage les IDM (-17%) et les AVC (-19%) que la mortalité (-4%). Les gliptines (combinaison de SAVOR TIMI 53, EXAMINE, TECOS) ont montré des effets globalement neutres sur la mortalité totale (0%), les IDM (-2%) et les AVC (-1%). L’empagliflozine (EMPA-REG OUTCOME) se singularise par un effet favorable nettement plus marqué sur la mortalité totale (-32 %) et CV (- 38%) que sur les IDM (-13%) ou les AVC (+18%). Conclusion : Les discordances observées suggèrent l’implication de mécanismes protecteurs différents selon les interventions testées. EMPA-REG OUTCOME, le seul essai démontrant un effet plus marqué sur la mortalité que sur les événements CV, suggère un mécanisme propre de l’inhibiteur des SGLT2. [less ▲]Detailed reference viewed: 35 (1 ULg)
Quelle est la stratégie idéale pour traiter l’hyperglycémie du diabète de type 2 ?
in Médecine des Maladies Métaboliques (2016), 10(2), 91-93Detailed reference viewed: 114 (2 ULg)
Les résultats de réduction de mortalité cardiovasculaire et totale avec l’empagliflozine peuvent-ils s’expliquer par un effet diurétique ?
in Diabètes & Métabolism (2016, March), 42Detailed reference viewed: 21 (2 ULg)
Implication du remodelage membranaire induit par les acides gras dans la régulation de l’activité de l’inflammasome NLRP3 dans les macrophages humains
Gianfrancesco, Marco ; ; et al
Conference (2016, March)Detailed reference viewed: 34 (9 ULg)
Le médicament du mois. Le dulaglutide (Trulicity®) : Nouvel agoniste des récepteurs du Glucagon-Like Peptide-1 en injection hebdomadaire pour traiter le diabète de type 2
in Revue Médicale de Liège (2016), 71
Summary : Dulaglutide (Trulicity®) is a new once-weekly agonist of Glucagon-Like Peptide-1 (GLP-1) receptors indicated in the treatment of type 2 diabetes. Phase III clinical trials in AWARD programme ... [more ▼]
Summary : Dulaglutide (Trulicity®) is a new once-weekly agonist of Glucagon-Like Peptide-1 (GLP-1) receptors indicated in the treatment of type 2 diabetes. Phase III clinical trials in AWARD programme demonstrated the efficacy and safety of dulaglutide in patients with type 2 diabetes treated by diet and exercise, metformin, a combination of metformin and a sulfonylurea or metformin and pioglitazone or even by supplements of prandial insulin. In the AWARD programme, dulaglutide (subcutaneous 0.75 or 1.5 mg once weekly) exerted a greater glucose-lowering activity than metformin, sitagliptin, exenatide or insulin glargine, and was non-inferior to liraglutide 1.8 mg once daily. Dulaglutide is currently reimbursed in Belgium after failure of and in combination with a dual oral therapy with metformin and a sulfonylurea or metformin and pioglitazone. [less ▲]Detailed reference viewed: 152 (3 ULg)
La vignette diagnostique de l’étudiant. L’importance du facteur temps et de la chronologie des événements dans l’anamnèse médicale
in Revue Médicale de Liège (2016), 71
Summary : Medical history taking represents a key step in the diagnostic approach. A structured interview with a special attention to the chronology of events is mandatory. The medical student often fails ... [more ▼]
Summary : Medical history taking represents a key step in the diagnostic approach. A structured interview with a special attention to the chronology of events is mandatory. The medical student often fails to use the information on time in an optimal way. The aim of this article is to draw the attention on a few key elements, especially the age of the patient, the duration of symptoms, the time of occurrence of complaints within the 24h period and, finally, how to interpret the simultaneous or sequential occurrence of two (or more) events. [less ▲]Detailed reference viewed: 32 (5 ULg)
Le médicament du mois. Insuline glargine 300 U/mL (Toujeo®)
in Revue Médicale de Liège (2016), 71
Summary : This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for ... [more ▼]
Summary : This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for the treatment of type 1 and type 2 diabetes in adults. Besides a threefold higher concentration compared to the classical insulin Lantus® (100 U/mL or Gla-100), both pharmacokinetic and pharmacodynamic profiles of Gla-300 are flatter and longer (more than 24 hours) and have a lesser intra-/inter-variability, which makes them more reproducible. Overall, Toujeo® offers the same hypoglycaemic efficacy and the same safety profile when compared with Lantus®. However, a lower risk of hypoglycaemia, especially at night, a slightly smaller weight gain and a better flexibility in the time of injection have been reported. The two insulin formulations are not bioequivalent and the daily insulin requirement is slightly higher with insulin Gla-300 than with insulin Gla-100. The shift from an already available basal insulin towards Toujeo® may require a dose adjustment and a reinforcement of blood glucose monitoring. [less ▲]Detailed reference viewed: 166 (8 ULg)
Body image discrepancy and subjective norm as mediators and moderators of the relationship between body mass index and quality of life
Pétré, Benoît ; Scheen, André ; et al
in Patient Preference and Adherence (2016), 10Detailed reference viewed: 18 (3 ULg)
Reappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics.
in Diabètes & Métabolism (2016)
AIMS: Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been associated with a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes and ... [more ▼]
AIMS: Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been associated with a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes and antecedents of cardiovascular disease. This effect was attributed to a diuretic (haemodynamic) rather than metabolic (antiatherogenic) effect. The aim of this review is to offer arguments that either support or challenge this 'diuretic hypothesis'. METHODS: The literature was scrutinized to: (1) examine the diuretic effects of SGLT2 inhibitors vs. hydrochlorothiazide as the reference diuretic; (2) analyze the effects of classic diuretics on cardiovascular outcomes and mortality in diabetic patients; and (3) reconsider some of the specific analyses of the EMPA-REG OUTCOME trial possibly related to a diuretic effect. RESULTS: The diuretic effect of empagliflozin has so far been poorly investigated, although SGLT2 inhibitors have actions distinct from those of classic diuretics. The effects of thiazide-like diuretics on cardiovascular and overall mortality have been limited in diabetic patients with hypertension, whereas the effects of mineralocorticoid receptor antagonists in subgroups of diabetic patients with heart failure were more impressive, but still largely inferior to those reported in EMPA-REG, where relative reductions in mortality with empagliflozin were observed in diabetic patients with or without heart failure, arterial hypertension, renal impairment or diuretic background therapy. CONCLUSION: Although the diuretic hypothesis was put forward to explain the remarkable reduction in mortality with empagliflozin in EMPA-REG, the available results do not support a major contribution of this mechanism, unless the specific diuretic effect of SGLT2 inhibitors turns out to be markedly different from those of classic diuretics. [less ▲]Detailed reference viewed: 33 (5 ULg)
Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.
in Diabetes Research & Clinical Practice (2016), 121
Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of ... [more ▼]
Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial. [less ▲]Detailed reference viewed: 18 (1 ULg)
SGLT2 Inhibitors: Benefit/Risk Balance.
in Current Diabetes Reports (2016), 16(10), 92
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet ... [more ▼]
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet/exercise, metformin, dual oral therapy or insulin. Three agents are available in Europe and the USA (canagliflozin, dapagliflozin, empagliflozin) and others are commercialized in Japan or in clinical development. SGLT2 inhibitors reduce glycated hemoglobin, with a minimal risk of hypoglycemia. They exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions. Empagliflozin showed remarkable reductions in cardiovascular/all-cause mortality and in hospitalization for heart failure in patients with previous cardiovascular disease. Positive renal outcomes were also shown with empagliflozin. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. Concern about a risk of ketoacidosis and bone fractures has been recently raised, which deserves caution and further evaluation. [less ▲]Detailed reference viewed: 20 (1 ULg)
Precision medicine: The future in diabetes care?
in Diabetes Research & Clinical Practice (2016), 117
Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic ... [more ▼]
Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic, pathophysiological and clinical point of view. Thus, the response to any antidiabetic medication may considerably vary between individuals. Numerous glucose-lowering agents, with different mechanisms of action, have been developed, a diversified armamentarium that offers the possibility of a patient-centred therapeutic approach. In the current clinical practice, a personalized approach is only based upon phenotype, taking into account patient and disease individual characteristics. If this approach may help increase both efficacy and safety outcomes, there remains considerable room for improvement. In recent years, many efforts were taken to identify genetic and genotype SNP's (Single Nucleotide Polymorphism's) variants that influence the pharmacokinetics, pharmacodynamics, and ultimately the therapeutic response of oral glucose-lowering drugs. This approach mainly concerns metformin, sulphonylureas, meglitinides and thiazolidinediones, with only scarce data concerning gliptins and gliflozins yet. However, the contribution of pharmacogenetics and pharmacogenomics to personalized therapy still needs to mature greatly before routine clinical implementation is possible. This review discusses both opportunities and challenges of precision medicine and how this new paradigm may lead to a better individualized treatment of T2D. [less ▲]Detailed reference viewed: 9 (1 ULg)
Diabetes: Time for reconciliation between cardiologists and diabetologists.
in Nature Reviews. Cardiology (2016)Detailed reference viewed: 30 (3 ULg)
DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects.
in Expert Opinion on Drug Metabolism & Toxicology (2016)
INTRODUCTION: Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl ... [more ▼]
INTRODUCTION: Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach. AREA COVERED: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations. EXPERT OPINION: There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. Combining the two pharmacological options is safe and does not induce hypoglycemia. The additional glucose-lowering effect is more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development. Bioequivalence of the two compounds given as FDC tablets was demonstrated when compared with coadministration of the individual tablets. FDCs could simplify the anti-hyperglycaemic therapy and improve drug compliance. [less ▲]Detailed reference viewed: 19 (2 ULg)
Assessment of cardiovascular risk of new drugs for the treatment of diabetes mellitus: risk assessment vs. risk aversion.
; ; et al
in European heart journal. Cardiovascular pharmacotherapy (2016), 2(3), 200-205
The Food and Drug Administration issued guidance for evaluating the cardiovascular risk of new diabetes mellitus drugs in 2008. Accumulating evidence from several completed trials conducted within this ... [more ▼]
The Food and Drug Administration issued guidance for evaluating the cardiovascular risk of new diabetes mellitus drugs in 2008. Accumulating evidence from several completed trials conducted within this framework raises questions as to whether requiring safety outcome studies for all new diabetes mellitus therapies remains justified. Given the burden of cardiovascular disease in patients with diabetes, the focus should shift towards cardiovascular outcome studies designed to evaluate efficacy (i.e. to determine the efficacy of a drug over placebo or standard care) rather than demonstrating that risk is not increased by a pre-specified safety margin. All stakeholders are responsible for ensuring that new drug approvals occur under conditions of appropriate safety and effectiveness. It is also a shared responsibility to avoid unnecessary hurdles that may compromise access to useful drugs and threaten the sustainability of health systems. It is critical to renew this debate so that stakeholders can collectively determine the optimal approach for developing new drugs to treat type 2 diabetes mellitus. [less ▲]Detailed reference viewed: 7 (0 ULg)