A randomized, double-blinded, parallel study to evaluate the dose-response of a monthly supplementation of 25000, 50000 or 100000 IU of vitamin D3 in subjects with deficiency in vitamin D
CAVALIER, Etienne ; JANDRAIN, Bernard ; et al
Poster (2014, April)Detailed reference viewed: 11 (3 ULg)
Résultats de l’enquête EDUDORA² sur le vécu du diabète de type 2 par les patients en fonction de l’estimation personnelle de leur qualité de vie
Hoge, Axelle ; Pétré, Benoît ; Streel, Sylvie et al
in Diabètes & Métabolism (2014, March), 40Detailed reference viewed: 62 (26 ULg)
Le diabète de type 2 vécu par le patient : résultats de l’enquête EDUDORA² étudiant les représentations des patients et des médecins généralistes
Hoge, Axelle ; Pétré, Benoît ; Streel, Sylvie et al
in Diabètes & Métabolism (2014, March), 40Detailed reference viewed: 69 (30 ULg)
Qu'apportent les nouvelles recommandations américaines à propos de la prise en charge des dyslipidémies en prévention cardiovasculaire ? Comparaison avec les recommandations européennes et belges
; ; 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 ▲]Detailed reference viewed: 86 (5 ULg)
Comment on Tsuda et al. Poor glycemic control is a major factor in the overestimation of glomerular filtration rate in diabetic patients. Diabetes care 2014;37:596-603
DELANAYE, Pierre ; SCHEEN, André
in Diabetes Care (2014), 37(4), 83Detailed reference viewed: 33 (3 ULg)
Faut-il mettre en doute les bénéfices du contrôle glycémique dans le diabète de type 2?
in Revue medicale suisse (2014), 10(439), 1531-2Detailed reference viewed: 21 (5 ULg)
Inflammasome NLRP3 et graisse viscerale.
; Legrand-Poels, Sylvie ; Piette, Jacques et al
in Revue medicale de Liege (2014), 69 Spec No
It is recognized that abdominal obesity is accompanied by a chronic low-grade inflammation that is involved in the pathogenesis of insulin resistance and type 2 diabetes. Metabolic syndrome and type 2 ... [more ▼]
It is recognized that abdominal obesity is accompanied by a chronic low-grade inflammation that is involved in the pathogenesis of insulin resistance and type 2 diabetes. Metabolic syndrome and type 2 diabetes are associated with an abnormal production of pro-inflammatory cytokines, an increased level of acute-phase proteins and an activation of inflammatory signalling pathways. These pro-inflammatory cytokines, mainly produced by adipose tissue macrophages, are involved in development of obesity-associated insulin resistance and in the progression from obesity to type 2 diabetes. Particularly, the interleukin-1 beta may play a key role through the activation of the NLRP3 inflammasome. Adipose tissue topography, more than the total amount of fat, may play an important pathogenic role. Indeed, the presence of metabolic abnormalities in obesity is associated with a deleterious immunological and inflammatory profile of visceral adipose tissue and with an increased activation of the NLRP3 inflammasome in macrophages infiltrating visceral adipose tissue. Targeting inflammation, especially NLRP3 inflammasome, may offer potential novel therapeutic perspectives in the prevention and treatment of type 2 diabetes. [less ▲]Detailed reference viewed: 20 (4 ULg)
Erratum to: Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus
in Clinical Pharmacokinetics (2014), 53(11), 1061Detailed reference viewed: 12 (0 ULg)
Pharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus.
in Clinical pharmacokinetics (2014), 53(9), 773-85
Patients with type 2 diabetes mellitus 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 ... [more ▼]
Patients with type 2 diabetes mellitus 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, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarises the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and their hepatic safety was carefully analysed in large clinical trials. Only mild changes in pharmacokinetic characteristics of DPP-4 inhibitors were observed in patients with different degrees of HI, presumably without major clinical relevance. GLP-1 receptor agonists have a renal excretion rather than liver metabolism. Specific pharmacokinetic data in patients with HI are only available for liraglutide. No significant changes in liver enzymes were reported with DPP-4 inhibitors or GLP-1 receptor agonists, alone or in combination with various other glucose-lowering agents, in clinical trials up to 2 years in length. On the contrary, preliminary data suggested that incretin-based therapies may be beneficial in patients with CLD, more particularly in the presence of non-alcoholic fatty liver disease. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, because of a lack of clinical experience with incretin-based therapies in these vulnerable patients. [less ▲]Detailed reference viewed: 24 (8 ULg)
Influence de l'Indice de Masse Corporelle sur les Perceptions et les Représentations de Sujets en Surpoids ou Obèses en Wallonie (Belgique) : Résultats de l'Etude EDUDORA²
Crutze, Céline ; Streel, Sylvie ; Donneau, Anne-Françoise et al
in Diabètes & Métabolism (2014), 40Detailed reference viewed: 46 (12 ULg)
Pharmacothérapie du sujet âgé: Primum non nocere!
in Revue medicale de Liege (2014), 69(5-6), 282-6
Elderly patients, having various chronic diseases, are generally exposed to polypharmacy that may lead to potential adverse events. The latter may be explained by pharmacokinetic and pharmacodynamic ... [more ▼]
Elderly patients, having various chronic diseases, are generally exposed to polypharmacy that may lead to potential adverse events. The latter may be explained by pharmacokinetic and pharmacodynamic particularities that render elderly individuals more vulnerable when exposed to certain medications. Recruitment of elderly patients in clinical trials is often limited, so that it is not always easy to determine the real benefit/risk ratio of pharmacotherapy in this population. Obviously, iatrogenicity is quite frequent. Therefore, in front of unexplained alterations of health status in an elderly individual, the physician should consider the possibility of a drug adverse effect. Because of this situation, the physician should envisage a reasonable drug prescription in an elderly patient. Especially, not only the initiation of drug therapy should be carefully analyzed, but also the opportunity to eventually stop a medication that may be useless or even dangerous. Rather polypharmacy per se, it is the inappropriate prescription that should be avoided in the elderly. [less ▲]Detailed reference viewed: 18 (3 ULg)
Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor.
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 ▲]Detailed reference viewed: 20 (2 ULg)
Déficiences hormonales du sujet âgé: faut-il les traiter?
; ; Scheen, André
in Revue medicale suisse (2014), 10(439), 1555-61558-61
Biological aging is characterized by a progressive loss of the secretion of various hormones, a phenomenon that leads some physicians to propose an anti-aging hormonal therapy. It is mandatory to ... [more ▼]
Biological aging is characterized by a progressive loss of the secretion of various hormones, a phenomenon that leads some physicians to propose an anti-aging hormonal therapy. It is mandatory to differentiate: 1) the physiological functional loss, which is a natural phenomenon without clear deleterious consequences on health and should not be compensated by the administration of hormones only to restore plasma levels similar to those measured in young people and 2) a pathological defect that deserves a replacement therapy to correct the endocrine deficiency and improve the health status of older individuals. This article considers the deficiencies in insulin, thyroid hormones, growth hormone, dehydroepiandrosterone (DHEA) and testosterone. For each hormone, a benefit/risk ratio of a so-called replacement therapy will be analyzed. [less ▲]Detailed reference viewed: 25 (3 ULg)
Effect of brivaracetam on CYP3A activity, measured by oral midazolam.
; ; Scheen, André
in Journal of clinical pharmacology (2014)
Brivaracetam is a synaptic vesicle protein 2A ligand in phase III development for epilepsy. A phase I, open-label, randomized study was conducted in 42 healthy male participants to assess the effect of ... [more ▼]
Brivaracetam is a synaptic vesicle protein 2A ligand in phase III development for epilepsy. A phase I, open-label, randomized study was conducted in 42 healthy male participants to assess the effect of brivaracetam on CYP3A activity using midazolam as a probe. Participants were randomized to oral brivaracetam 5, 50, or 150 mg/day from Day 8 to Day 14. A single oral dose (7.5 mg) of midazolam was administered on Days 1, 13, and 20, and full pharmacokinetic profiles were obtained. For all brivaracetam doses, the areas under the plasma concentration-time curves from 0 to infinity (AUCinf ) for midazolam and 1'-hydroxymidazolam were similar on Days 13 and 20 compared with Day 1. Following brivaracetam 150 mg/day, the Day 13/Day 1 AUCinf ratio (90% confidence interval) was 1.09 (0.97, 1.21) and 1.04 (0.93, 1.17) for midazolam and 1'-hydroxymidazolam, respectively. For the Day 20/Day 1 comparison, the corresponding AUCinf ratios were 1.10 (0.98, 1.23) and 1.07 (0.97, 1.18). Maximum midazolam plasma concentration was increased on both Day 13 and Day 20 vs. Day 1 but the relevance of this finding was unclear. This study indicates that brivaracetam up to 150 mg/day has no significant inducing or inhibiting effect on CYP3A activity. [less ▲]Detailed reference viewed: 9 (0 ULg)
Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence.
Scheen, André ; Paquot, Nicolas
in Diabetes & metabolism (2014), 40(6 Suppl 1), 4-11
Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by ... [more ▼]
Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by facilitating glucose excretion through the kidneys. However, this simple renal mechanism that results in sustained glucose urinary loss leads to more complex indirect metabolic effects. First, by reduction of chronic hyperglycaemia and attenuation of glucose toxicity, SGLT-2 inhibitors can improve both insulin secretion by beta cells and peripheraltissue insulin sensitivity. In the case of canagliflozin, because of low-potency SGLT1 inhibition, a non-renal (intestinal) effect may also be considered, which may contribute to better control of postprandial hyperglycaemia, although this contribution remains to be better analyzed in humans. Second, chronic glucose loss most probably leads to compensatory mechanisms. One of them, although not well evidenced in humans, might involve an increase in energy intake, an effect that may limit weight loss in the long run. Another could be an increase in endogenous glucose production, most probably driven by increased glucagon secretion, which may somewhat attenuate the glucoselowering effect. Nevertheless, despite these compensatory mechanisms and most probably because of the positive effects of the reduction in glucotoxicity, SGLT-2 inhibitors exert clinically relevant glucose-lowering activity while promoting weight loss, a unique dual effect among oral antidiabetic agents. Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus. [less ▲]Detailed reference viewed: 15 (1 ULg)
Editorial. SGLT-2 receptor inhibitors: An opportunity to revise our therapeutic strategy for type 2 diabetes?
; Scheen, André
in Diabetes & metabolism (2014), 40(6 Suppl 1), 1-3Detailed reference viewed: 10 (1 ULg)
Interet d'une combinaison agoniste des recepteurs du GLP-1 et insuline basale dans le traitement du diabete de type 2.
Scheen, André ; Paquot, Nicolas
in Revue medicale suisse (2014), 10(439), 1549-54
The complex pathophysiology of type 2 diabetes and its natural evolution, characterized by a progressive loss of glucose control due to the exhaustion of insulin secretion, lead to consider new ... [more ▼]
The complex pathophysiology of type 2 diabetes and its natural evolution, characterized by a progressive loss of glucose control due to the exhaustion of insulin secretion, lead to consider new complementary therapeutic options. Even at the insulin-requiring stage, the addition of a glucagon-like peptide-1 (GLP-1) receptor agonist is beneficial. Besides their incretinomimetic activity (which may decrease with the loss of beta-cell mass/function), GLP-1 receptor agonists reduce glucagon secretion, slow down gastric emptying and diminish appetite through a central effect. These combined effects permit to improve glucose control, while reducing daily insulin doses, together with less weight gain (or even weight loss) and generally less hypoglycaemia. Fixed insulin glargine-lixisenatide and insulin degludec-liraglutide are currently in development. [less ▲]Detailed reference viewed: 20 (1 ULg)
Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes.
in Clinical pharmacokinetics (2014)
The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic ... [more ▼]
The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic agents have limitations in patients with CKD, incretin-based therapies are increasingly used for the management of T2DM. This review analyses (1) the influence of CKD on the pharmacokinetics of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists; and (2) the efficacy/safety profile of these agents in clinical practice when prescribed in patients with both T2DM and CKD. Most DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin) are predominantly excreted by the kidneys. Thereby, pharmacokinetic studies showed that total exposure to the drug is increased in proportion to the decline of GFR, leading to recommendations for appropriate dose reductions according to the severity of CKD. In these conditions, clinical studies reported a good efficacy and safety profile in patients with CKD. In contrast, linagliptin is eliminated by a predominantly hepatobiliary route. As a pharmacokinetic study showed only minimal influence of decreased GFR on total exposure, no dose adjustment of linagliptin is required in the case of CKD. The experience with GLP-1 receptor agonists in patients with CKD is more limited. Exenatide is eliminated by renal mechanisms and should not be given in patients with severe CKD. Liraglutide is not eliminated by the kidney, but it should be used with caution because of the limited experience in patients with CKD. Only limited pharmacokinetic data are also available for lixisenatide, exenatide long-acting release (LAR) and other once-weekly GLP-1 receptor agonists in current development. Several case reports of acute renal failure have been described with GLP-1 receptor agonists, probably triggered by dehydration resulting from gastrointestinal adverse events. However, increasing GLP-1 may also exert favourable renal effects that could contribute to reducing the risk of diabetic nephropathy. In conclusion, the already large reassuring experience with DPP-4 inhibitors in patients with CKD offers new opportunities to the clinician, whereas more caution is required with GLP-1 receptor agonists because of the limited experience in this population. [less ▲]Detailed reference viewed: 22 (1 ULg)