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See detailLes nouvelles recommandations Europeennes pour le traitement des dyslipidemies en prevention cardiovasculaire.
Descamps, O. S.; De Backer, G.; Annemans, L. et al

in Revue Médicale de Liège (2012), 67(3), 118-27

The new guidelines from the European Atherosclerosis Society and the European Society of Cardiology include a number of updated items. In this paper, we summarize 4 of these changes that we consider to be ... [more ▼]

The new guidelines from the European Atherosclerosis Society and the European Society of Cardiology include a number of updated items. In this paper, we summarize 4 of these changes that we consider to be the most pertinent. Firstly, cardiovascular risk is now stratified according to 4 (previously 2) categories: "very high risk" (patients with cardiovascular disease, patients with diabetes > 40 years old who have at least one other risk factor, patients with kidney failure, or patients in primary prevention with a SCORE value > or = 10%); "high risk" (patients in primary prevention with a SCORE value > or = 5% and < 10% or patients with a particularly serious risk factor such as familial hypercholesterolaemia or patients with diabetes < 40 years old without any other risk factor); "moderate risk" (primary prevention with SCORE > or = 1% and < 5%); and "low risk" (primary prevention with SCORE < 1%). The SCORE value for patients in primary prevention is estimated using the SCORE table (calibrated for Belgium). Risk in this table may now be corrected according to HDL cholesterol level. Secondly, the therapeutic targets for each category are now more stringent: LDL cholesterol < 70 mg/dl (or reduced by at least 50%) if the risk is "very high"; < 100 mg/dl if the risk is "high"; and < 115 mg/dl if the risk is "moderate". Thirdly, for patients at "high" or "very high" risk, particularly in patients with combined dyslipidaemia, two further therapeutic targets should be considered: non-HDL cholesterol and apolipoprotein B levels. Fourthly, the follow-up of efficacy (lipid profile) and tolerance (hepatic and muscular enzymes) is described in more details so as to harmonize case management in clinical practice. [less ▲]

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See detailLa vignette therapeutique de l'etudiant: Quelles cibles glycemiques et lipidiques viser chez un patient diabetique de type 2?
Paquot, Nicolas ULg; SCHEEN, André ULg

in Revue Médicale de Liège (2012), 67(2), 98-103

Patients with type 2 diabetes are at high cardiovascular risk and require a global management targeting all risk factors. Target values for blood pressure have been discussed in a previous paper. The ... [more ▼]

Patients with type 2 diabetes are at high cardiovascular risk and require a global management targeting all risk factors. Target values for blood pressure have been discussed in a previous paper. The present clinical case summarizes the most important arguments concerning the choice of the target values for glucose control (glycated haemoglobin or HbA1c) and lipid management. As far as glucose control is concerned, the objective should be individually adjusted, based on the benefits/risks ratio, with a less stringent HbA1c level in presence of coronary heart disease and risk of severe hypoglycaemia. However, in absence of these two risks factors, the objective should be reinforced (HbA1c < 7%), essentially to prevent or retard microangiopathic lesions. As far as lipid management is concerned, the most crucial goal remains LDL cholesterol lowering, with a target value < 100 mg/dL in patients at high cardiovascular risk and <70 mg/dL in patients at very high risk, according to the recent European guidelines. Dyslipidaemia related to the metabolic syndrome (hypertriglyceridaemia, low HDL cholesterol) may also represent a therapeutic target (non-HDL cholesterol), although evidence is mostly missing in the literature. [less ▲]

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See detailLe medicament du mois: Linagliptine (Trajenta): un inhibiteur selectif de la DPP-4 a elimination renale negligeable.
SCHEEN, André ULg; Van Gaal, L. F.

in Revue Médicale de Liège (2012), 67(2), 91-7

Linagliptin (Trajenta) is a selective inhibitor of dipeptidyl peptidase-4, an enzyme that degrades two incretin hormones, GLP-1 ("Glucagon-Like Peptide-1") and GIP ("Glucose-dependent Insulinotropic ... [more ▼]

Linagliptin (Trajenta) is a selective inhibitor of dipeptidyl peptidase-4, an enzyme that degrades two incretin hormones, GLP-1 ("Glucagon-Like Peptide-1") and GIP ("Glucose-dependent Insulinotropic Polypeptide"). As other molecules belonging to this pharmacological class, linagliptin improves blood glucose control of type 2 diabetic patients, without increasing hypoglycaemic risk, without promoting weight gain and with a good clinical and biological tolerance profile. Both efficacy and safety have been demonstrated in randomized controlled trials as monotherapy or in combination with other glucose-lowering agents, independent of demographic or clinical patient's characteristics. The pharmacokinetics specificity of linagliptin comprises its biliary excretion, with low hepatic metabolism (no drug-drug interactions) and, in contrast to other gliptins, its negligible renal elimination. Because of these favourable properties, linagliptin may be used without dose adjustment (5 mg once a day) in patients with renal impairment, as well as in elderly people. [less ▲]

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See detailMetformin + saxagliptin for type 2 diabetes.
SCHEEN, André ULg

in Expert Opinion on Pharmacotherapy (2012), 13(1), 139-46

INTRODUCTION: Metformin is considered as the first-line drug therapy for the management of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors, by promoting insulin secretion and reducing glucagon ... [more ▼]

INTRODUCTION: Metformin is considered as the first-line drug therapy for the management of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors, by promoting insulin secretion and reducing glucagon secretion in a glucose-dependent manner, offer new opportunities for oral therapy after failure of metformin. AREAS COVERED: An updated review of the literature demonstrates that saxagliptin, a DPP-4 inhibitor, and metformin may be administered together, separately or in fixed-dose combination (FDC), either as saxagliptin added to metformin or as initial combination in drug-naive patients. Both compounds exert complementary pharmacodynamic actions leading to better improvement in blood glucose control (fasting plasma glucose, postprandial glucose, HbA1c) than either compound separately. Adding saxagliptin to metformin monthotherapy results in a consistent, sustained and safe reduction in HbA1c levels. Tolerance is excellent without hypoglycemia or weight gain. EXPERT OPINION: The combination saxaglitpin plus metformin may be used as first-line or second-line therapy in the management of type 2 diabetes, especially as a valuable alternative to the classical metformin-sulfonylurea combination. [less ▲]

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See detailQuelles cibles glycémiques et lipidiques viser chez un patient diabétique de type 2 ?
PAQUOT, Nicolas ULg; SCHEEN, André ULg

in Revue Médicale de Liège (2012), 67

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See detailDiabète et Ramadan : représentations et pratiques de santé des patients et des soignants et intérêts de l'éducation thérapeutique du patient
Smaoui, N; Böhme, P; Collin, JF et al

in Diabètes & Métabolism (2012), 38(2), 47-48

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See detailCampagnes de sensibilisation au dépistage du diabète de type 2 dans les pharmacies. Comparaison de deux approches : glycémie capillaire et grille Findrisc
Böhme, P; Agrinier, N; Badia, M et al

in Diabètes & Métabolism (2012), 38(2), 7

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See detailA review of gliptins in 2011.
SCHEEN, André ULg

in Expert Opinion on Pharmacotherapy (2012), 13(1), 81-99

INTRODUCTION: Dipeptidylpeptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). AREAS COVERED: This paper is an updated review, providing an analysis of both the ... [more ▼]

INTRODUCTION: Dipeptidylpeptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). AREAS COVERED: This paper is an updated review, providing an analysis of both the similarities and the differences between the various compounds known as gliptins, currently used in the clinic (sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin). This paper discusses the pharmacokinetic and pharmacodynamic characteristics of gliptins; both the efficacy and safety profiles of gliptins in clinical trials (compared with classical glucose-lowering agents), given as monotherapy or in combination, including in special populations; the positioning of DPP-4 inhibitors in the management of T2DM in recent guidelines; and various unanswered questions and perspectives. EXPERT OPINION: The role of DPP-4 inhibitors in the therapeutic armamentarium of T2DM is evolving, as their potential strengths and weaknesses become better defined. Future critical issues may include the durability of glucose control, resulting from better beta-cell protection, positive effects on cardiovascular outcomes and long-term safety issues. [less ▲]

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See detailSaxagliptin plus metformin combination in patients with type 2 diabetes and renal impairment.
SCHEEN, André ULg

in Expert Opinion on Drug Metabolism & Toxicology (2012), 8(3), 383-94

INTRODUCTION: A metformin plus saxagliptin fixed-dose combination is now proposed to clinicians. Furthermore, saxagliptin's license was recently extended to include diabetic patients with moderate or ... [more ▼]

INTRODUCTION: A metformin plus saxagliptin fixed-dose combination is now proposed to clinicians. Furthermore, saxagliptin's license was recently extended to include diabetic patients with moderate or severe renal impairment (RI). However, metformin is still contraindicated in patients with RI. AREAS COVERED: This review analyses the pro and contra of using a combination of saxagliptin and metformin (separately or as a fixed-dose combination) in type 2 diabetic patients with moderate or severe RI. An extensive literature search of all pharmacokinetic data and efficacy/safety profile of metformin and saxagliptin in subjects with RI was performed. EXPERT OPINION: Since both metformin and saxagliptin are excreted via the kidney, dose adjustment is required in case of moderate-to-severe RI (half dose of saxagliptin). However, major discrepancies exist between guidelines (metformin excluded in case of RI because of the risk of lactic acidosis) and real life (metformin widely prescribed in patients with some degree of RI). Physicians should weigh the benefit/risk ratio carefully before deciding to prescribe or withdraw the combination metformin plus saxagliptin in patients with stable RI. A redefinition of contraindications to metformin will enable more physicians to prescribe within guidelines and to administer saxagliptin combined with metformin in more patients who clearly may benefit from this combination. [less ▲]

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See detailDifferential effects of olanzapine and risperidone on plasma adiponectin levels over time: Results from a 3-month prospective open-label study.
Wampers, M.; Hanssens, L.; van Winkel, R. et al

in European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (2012), 22

Second-generation antipsychotics (SGA), especially clozapine and olanzapine, are associated with an increased metabolic risk. Recent research showed that plasma adiponectin levels, an adipocyte-derived ... [more ▼]

Second-generation antipsychotics (SGA), especially clozapine and olanzapine, are associated with an increased metabolic risk. Recent research showed that plasma adiponectin levels, an adipocyte-derived hormone that increases insulin sensitivity, vary in the same way in schizophrenic patients as in the general population according to gender, adiposity and metabolic syndrome (MetS). The aim of the present study was to investigate whether different SGAs differentially affect plasma adiponectin levels independent of body mass index (BMI) and MetS status. 113 patients with schizophrenia (65.5% males, 32.3years old) who were free of antipsychotic medication were enrolled in this open-label prospective single-center study and received either risperidone (n=54) or olanzapine (n=59). They were followed prospectively for 12weeks. Average daily dose was 4.4mg/day for risperidone and 17.4mg/day for olanzapine. Plasma adiponectin levels as well as fasting metabolic parameters were measured at baseline, 6weeks and 12weeks. The two groups had similar baseline demographic and metabolic characteristics. A significant increase in body weight was observed over time. This increase was significantly larger in the olanzapine group than in the risperidone group (+7.0kg versus +3.1kg, p<0.0002). Changes in fasting glucose and insulin levels and in HOMA-IR, an index of insulin resistance, were not significantly different in both treatment groups. MetS prevalence increased significantly more in the olanzapine group as compared to the risperidone groups where the prevalence did not change over time. We observed a significant (p=0.0015) treatment by time interaction showing an adiponectin increase in the risperidone-treated patients (from 10,154 to 11,124ng/ml) whereas adiponectin levels decreased in olanzapine treated patients (from 11,280 to 8988ng/ml). This effect was independent of BMI and the presence/absence of MetS. The differential effect of antipsychotic treatment (risperidone versus olanzapine) on plasma adiponectin levels over time, independent of changes in waist circumference and antipsychotic dosing, suggests a specific effect on adipose tissues, similar to what has been observed in animal models. The observed olanzapine-associated reduction in plasma adiponectin levels may at least partially contribute to the increased metabolic risk of olanzapine compared to risperidone. [less ▲]

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See detailInhibiteurs du cotransporteur du glucose SGLT rénal pour traiter le diabète de type 2
SCHEEN, André ULg; RADERMECKER, Régis ULg; ERNEST, Philippe ULg et al

in Revue Médicale Suisse (2011), 7(306), 1621-1629

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See detailOlmesartan for the delay or prevention of microalbuminuria in type 2 diabetes
Haller H; Ito S; Izzo JL Jr, et al

in New England Journal of Medicine [=NEJM] (2011), 364

BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or ... [more ▼]

BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. METHODS: In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angiotensin-converting-enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points. RESULTS: The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P=0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients (0.7%) as compared with 3 patients (0.1%) (P=0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P=0.02). CONCLUSIONS: Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.). [less ▲]

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See detailEditorial. Le cancer du sein.
JERUSALEM, Guy ULg; SCHEEN, André ULg

in Revue Médicale de Liège (2011), 66(5-6), 225-228

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See detailHypocortisolism induces chronic respiratory failure
PIRLET, Charles ULg; BECK, Emmanuel ULg; SCHEEN, André ULg et al

in Respiratory Medicine (2011), 4(3), 107-108

Hypocortisolism is an uncommon condition. Its association with myopathy and respiratoryfailure has only rarely been described. We report the case of a 52 year-old woman presenting with progressive ... [more ▼]

Hypocortisolism is an uncommon condition. Its association with myopathy and respiratoryfailure has only rarely been described. We report the case of a 52 year-old woman presenting with progressive dyspnoea. Work-up revealed a severe restrictive syndrome with hypoxaemia. Further investigations showed hypocortisolism of pituitary origin. Response to hydrocortisone allowed us to conclude to an unusual case of hypocortisolic myopathy affecting the respiratory muscles. [less ▲]

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See detailPrevalence of the metabolic syndrome in Luxembourg according to the Joint Interim Statement definition estimated from the ORISCAV-LUX study.
Alkerwi, Ala'a; Donneau, Anne-Françoise ULg; Sauvageot, Nicolas et al

in BMC Public Health (2011), 11(1), 4

ABSTRACT: BACKGROUND: The prevalence of the metabolic syndrome (MS) has been determined in many countries worldwide but never in Luxembourg. This research aimed to 1) establish the gender- and age ... [more ▼]

ABSTRACT: BACKGROUND: The prevalence of the metabolic syndrome (MS) has been determined in many countries worldwide but never in Luxembourg. This research aimed to 1) establish the gender- and age-specific prevalence of MS and its components in the general adult population of Luxembourg, according to the most recent Joint Interim Statement (JIS) definition, by using both the high and low cut-off points to define abdominal obesity, and 2) compare and assess the degree of agreement with the Revised National Cholesterol Education Programme-Adult Treatment Panel III (R-ATPIII) and the International Diabetes Federation (IDF) definitions. METHODS: A representative stratified random sample of 1349 European subjects, aged 18-69 years, participated to ORISCAV-LUX survey. Logistic regression and odds ratios (OR) were used to study MS prevalence with respect to gender and age. The Framingham risk score (FRS) to predict the 10-year coronary heart disease (CHD) risk was calculated to compare the proportion of MS cases below or above 20%, according to both high and low waist circumference (WC) thresholds. Cohen's kappa coefficient (kappa) was utilized to measure the degree of agreement between MS definitions. RESULTS: The prevalence of the MS defined by the JIS was 28.0% and 24.7% when using the low (94/80) and the high (102/88) WC cut-off points, respectively. The prevalence was significantly higher in men than in women (OR = 2.6 and 2.3 for the low and high WC thresholds), as were all components of the MS except abdominal obesity measured by both thresholds. It also increased with age (OR values in age categories ranging from 2.7 to 28 when compared to the younger subjects for low WC and from 3.3 to 31 for the high WC cut-offs). The 10-year predicted risk of CHD by FRS did not depend on the threshold used. Globally, excellent agreement was observed between the three definitions of MS (kappa= 0.89), in particular between JIS and IDF (kappa = 0.93). Agreement was significantly higher in women than in men, and differed between age groups. CONCLUSION: Regardless of the definition used, the adult population of Luxembourg reveals a high MS prevalence. Our findings contribute to build evidence regarding the definitive construct of the MS, to help selecting the waist circumference thresholds for Europid populations, and to support the need to revise the guidelines for abdominal obesity levels. [less ▲]

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See detailDPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials.
SCHEEN, André ULg

in Diabètes & Métabolism (2011)

Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that ... [more ▼]

Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials. [less ▲]

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