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See detailRationnel en faveur d'une combinaison insuline basale-incretine pour traiter le diabete de type 2.
Scheen, André ULg; Paquot, Nicolas ULg

in Revue medicale de Liege (2013), 68(11), 562-8

Type 2 diabetes is characterized by an insulin secretory defect that cannot compensate for insulin resistance. Such relative defect is present in the fasting state (insufficient basal insulin levels) and ... [more ▼]

Type 2 diabetes is characterized by an insulin secretory defect that cannot compensate for insulin resistance. Such relative defect is present in the fasting state (insufficient basal insulin levels) and contributes to overnight hyperglycaemia; it is even more pronounced in the postprandial state when it is then the main responsible factor for hyperglycaemia following meals. An original approach to correct these two disturbances is to propose a therapy combining the injection of a basal insulin (most commonly at bedtime to better control fasting glycaemia) and the administration of an incretin-based medication to potentiate insulin response to the three main meals, without inducing hypoglycaemia. This latter effect can be obtained either by blocking the degradation of incretin hormones with an oral inhibitor of dipeptidyl peptidase-4 (gliptin), or by injecting an agonist of glucagon-like peptide-1 (GLP-1) receptors. These basal insulin-incretin combined therapies are well validated in various controlled trials and observational studies. Lixisenatide is the first GLP-1 receptor agonist being reimbursed in this specific indication of combination with basal insulin in Belgium. [less ▲]

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See detailLe praticien face aux addictions dans tous leurs etats.
SCHEEN, André ULg; Pitchot, William

in Revue medicale de Liege (2013), 68(5-6), 209-10

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See detail((workaholism)): la dependance au travail, une autre forme d'addiction.
SCHEEN, André ULg

in Revue medicale de Liege (2013), 68(5-6), 371-6

Workaholism belongs to the behavioural addictions, also called ((without substances)) addictions, and is rather common in our society. The differential diagnosis must distinguish a hard worker, who has ... [more ▼]

Workaholism belongs to the behavioural addictions, also called ((without substances)) addictions, and is rather common in our society. The differential diagnosis must distinguish a hard worker, who has pleasure in his/her job, still profits from leisure time and maintains an excellent quality of life, from a true workaholic, who is prisoner of this compulsive behaviour that has negative consequences on his mental and physical health, his social and familial relationships and finally, his work performance itself. We describe here the various typologies of this mental disorder, its mode of evolution, its diagnostic approach, its multiple negative consequences for both patient and family as well as the main principles of management based on cognitive-behavioural therapy of this disorder that may be considered as a true addiction. [less ▲]

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See detailGLP-1 receptor agonists or DPP-4 inhibitors: How to guide the clinician?
SCHEEN, André ULg

in Annales d'Endocrinologie (2013)

Pharmacological treatment of type 2 diabetes has been enriched during recent years, with the launch of incretin therapies targeting glucagon-like peptide-1 (GLP-1). Such medications comprise either GLP-1 ... [more ▼]

Pharmacological treatment of type 2 diabetes has been enriched during recent years, with the launch of incretin therapies targeting glucagon-like peptide-1 (GLP-1). Such medications comprise either GLP-1 receptor agonists, with short (one or two daily injections: exenatide, liraglutide, lixisenatide) or long duration (one injection once weekly: extended-released exenatide, albiglutide, dulaglutide, taspoglutide); or oral compounds inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme that inactives GLP-1, also called gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin). Although both pharmacological approaches target GLP-1, important differences exist concerning the mode of administration (subcutaneous injection versus oral ingestion), the efficacy (better with GLP-1 agonists), the effects on body weight and systolic blood pressure (diminution with agonists versus neutrality with gliptins), the tolerance profile (nausea and possibly vomiting with agonists) and the cost (higher with GLP-1 receptor agonists). Both agents may exert favourable cardiovascular effects. Gliptins may represent a valuable alternative to a sulfonylurea or a glitazone after failure of monotherapy with metformin while GLP-1 receptor agonists may be considered as a good alternative to insulin (especially in obese patients) after failure of a dual oral therapy. However, this scheme is probably too restrictive and modalities of using incretins are numerous, in almost all stages of type 2 diabetes. Physicians may guide the pharmacological choice based on clinical characteristics, therapeutic goals and patient's preference. [less ▲]

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See detailQuels benefices antitumoraux attendre de la metformine ?
Beck, Emmanuel; SCHEEN, André ULg

in Annales d'Endocrinologie (2013), 74(2), 137-47

With the better management of cardiovascular risk factors, cancer plays an increasing role in the causes of death among patients with type 2 diabetes. Numerous epidemiological cohort and case-control ... [more ▼]

With the better management of cardiovascular risk factors, cancer plays an increasing role in the causes of death among patients with type 2 diabetes. 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 (sulfonylureas, insulin). Such beneficial effect is observed almost whatever the type of cancer, but seems to be more prominent in case of gastrointestinal and breast cancers. Several studies showed a significant relationship between the amplitude of the protection against cancer, on the one hand, and the daily dose of metformin and the duration of exposure, on the other hand. 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. Several meta-analyses recently confirmed that metformin therapy reduces the incidence of cancers and cancer-related mortality. 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. 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, independently of the presence of diabetes. [less ▲]

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See detailChirurgie bariatrique chez le patient diabétique de type 1 : résultats d’une expérience limitée.
FRANCK, Marie ULg; DE FLINES, Jenny ULg; PAQUOT, Nicolas ULg et al

in Diabète & Métabolisme (2013), 39(suppl), 102

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See detailLa vignette diagnostique de l'etudiant. Mise au point d'un patient consultant pour obesite.
De Flines, J.; Rorive, M.; Esser, Nathalie ULg et al

in Revue Médicale de Liège (2013), 68(3), 148-53

Obesity is increasingly prevalent in our society and medical consultations for evaluation and management of weight excess are frequent. Before considering a therapeutic strategy, a careful initial ... [more ▼]

Obesity is increasingly prevalent in our society and medical consultations for evaluation and management of weight excess are frequent. Before considering a therapeutic strategy, a careful initial clinical assessment is mandatory. The diagnostic approach of an obese person should be similar as for any other chronic pathology. The objectives of the present clinical description are to report the main steps of an exhaustive anamnesis, the signs to be more specifically detected at the clinical examination and the other useful investigations to be programmed at first glance in a person who is visiting his/her medical doctor because of obesity. Based upon the data collected during this careful evaluation, therapeutic modalities may be defined, ideally in the frame of a multidisciplinary approach. [less ▲]

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See detailPremiers enseignements de l’étude DESCENDANCE : prévalence des dysglycémies méconnues chez des apparentés de diabétiques de type 2 sur deux générations
Cosson, E; Gourdy, p; Penformis, A et al

in Résumés des communications de la réunion scientifique de la SFD 2013 (2013)

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See detailCardiovascular effects of gliptins.
SCHEEN, André ULg

in Nature Reviews. Cardiology (2013), 10(2), 73-84

Dipeptidyl peptidase 4 (DPP-4) inhibitors (commonly referred to as gliptins) are a novel class of oral antihyperglycaemic agents with demonstrated efficacy in the treatment of type 2 diabetes mellitus ... [more ▼]

Dipeptidyl peptidase 4 (DPP-4) inhibitors (commonly referred to as gliptins) are a novel class of oral antihyperglycaemic agents with demonstrated efficacy in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data and mechanistic studies have indicated a possible beneficial action on blood vessels and the heart, via both glucagon-like peptide 1 (GLP-1)-dependent and GLP-1-independent effects. DPP-4 inhibition increases the concentration of many peptides with potential vasoactive and cardioprotective effects. Clinically, DPP-4 inhibitors improve several risk factors in patients with T2DM. They improve blood glucose control (mainly by reducing postprandial glycaemia), are weight neutral (or even induce modest weight loss), lower blood pressure, improve postprandial lipaemia, reduce inflammatory markers, diminish oxidative stress, and improve endothelial function. Some positive effects on the heart have also been described in patients with ischaemic heart disease or congestive heart failure, although their clinical relevance requires further investigation. Post-hoc analyses of phase II-III, controlled trials suggest a possible cardioprotective effect with a trend for a lower incidence of major cardiovascular events with gliptins than with placebo or active agents. However, the actual relationship between DPP-4 inhibition and cardiovascular outcomes remains to be proven. Major prospective clinical trials with predefined cardiovascular outcomes and involving various DPP-4 inhibitors are now underway in patients with T2DM and a high-risk cardiovascular profile. [less ▲]

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See detailGliptins (dipeptidyl peptidase-4 inhibitors) and risk of acute pancreatitis.
SCHEEN, André ULg

in Expert Opinion on Drug Safety (2013), 12(4), 545-57

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) play an increasing role in the management of type 2 diabetes. Such incretin-based therapies offer some advantages over other glucose ... [more ▼]

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) play an increasing role in the management of type 2 diabetes. Such incretin-based therapies offer some advantages over other glucose-lowering agents, but might be associated with an increased risk of acute pancreatitis. Areas covered: An extensive literature search was performed to analyze clinical cases of acute pancreatitis reported in the literature or to the Food and Drug Administration (FDA), in randomized clinical trials, and in observational studies with five DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin. Expert opinion: An increased risk of pancreatitis has been reported in diabetic versus nondiabetic patients. Several anecdotal clinical cases of pancreatitis have been reported with sitagliptin and vildagliptin and an increased relative risk reported to the FDA with sitagliptin versus other comparators, but reporting bias cannot be excluded. In rather short-term clinical trials with well-selected diabetic patients, no increased risk of acute pancreatitis has been observed with any of the five commercialized DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin. Similarly, real-life cohort studies showed no increased incidence of pancreatitis with gliptins compared with other glucose-lowering agents, a finding recently challenged by a case- control study. These results must be confirmed in postmarketing surveillance programs and in ongoing large prospective trials with cardiovascular outcomes. [less ▲]

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See detailLes gliptines, une nouvelle mode?
SCHEEN, André ULg

in Revue du Praticien (La) (2013), 63(3), 304-5

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See detailCardiovascular effects of dipeptidyl peptidase-4 inhibitors: From risk factors to clinical outcomes.
SCHEEN, André ULg

in Postgraduate Medicine (2013), 125(3), 7-20

Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are oral incretin-based glucose-lowering agents with proven efficacy and safety in the management of type 2 diabetes mellitus (T2DM). In addition ... [more ▼]

Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are oral incretin-based glucose-lowering agents with proven efficacy and safety in the management of type 2 diabetes mellitus (T2DM). In addition, preclinical data and mechanistic studies suggest a possible additional non-glycemic beneficial action on blood vessels and the heart, via both glucagon-like peptide-1-dependent and glucagon-like peptide-1-independent effects. As a matter of fact, DPP-4 inhibitors improve several cardiovascular risk factors: they improve glucose control (mainly by reducing the risk of postprandial hyperglycemia) and are weight neutral; may lower blood pressure somewhat; improve postprandial (and even fasting) lipemia; reduce inflammatory markers; diminish oxidative stress; improve endothelial function; and reduce platelet aggregation in patients with T2DM. In addition, positive effects on the myocardium have been described in patients with ischemic heart disease. Results of post hoc analyses of phase 2/3 controlled trials suggest a possible cardioprotective effect with a trend (sometimes significant) toward lower incidence of major cardiovascular events with sitagliptin, vildagliptin, saxagliptin, linagliptin, or alogliptin compared with placebo or other active glucose-lowering agents. However, the definite relationship between DPP-4 inhibition and better cardiovascular outcomes remains to be proven. Major prospective clinical trials involving various DPP-4 inhibitors with predefined cardiovascular outcomes are under way in patients with T2DM and a high-risk cardiovascular profile: the Sitagliptin Cardiovascular Outcome Study (TECOS) on sitagliptin, the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 trial on saxagliptin, the Cardiovascular Outcomes Study of Alogliptin in Subjects With Type 2 Diabetes and Acute Coronary Syndrome (EXAMINE) trial on alogliptin, and the Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes (CAROLINA) on linagliptin. If these trials confirm that a DPP-4 inhibitor can reduce the cardiovascular burden of T2DM, it would be major progress that would dramatically influence the management of the disease. [less ▲]

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See detailL'hypotension orthostatique: 2eme partie. Epidemiologie, complications et traitements.
Tyberghein, M.; Philips, J.-C.; Krzesinski, Jean-Marie ULg et al

in Revue Médicale de Liège (2013), 68(4), 163-70

Orthostatic hypotension (OH) is a rather common phenomenon in clinical practice. It may occur in 5-10 % of normal individuals, but its prevalence increases with age and various pathologies, so that it may ... [more ▼]

Orthostatic hypotension (OH) is a rather common phenomenon in clinical practice. It may occur in 5-10 % of normal individuals, but its prevalence increases with age and various pathologies, so that it may rise above 35 % in certain subgroups of patients. OH is associated with various comorbidities, in particular cardio-cerebro-vascular accidents and falls (especially in the elderly), and may even increase mortality. It is, however, difficult to determine whether OH is simply a marker of frailty or whether it is really a risk factor. OH treatment involves physical manoeuvres or medications, which aim at inducing a peripheral vasoconstriction (midodrine, etilefrine) or an increase of circulating blood volume (9-alpha-fluohydrocortisone). However, their use should be cautious, because of a risk of arterial hypertension in supine position. [less ▲]

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See detailLa vignette diagnostique de l'etudiant. Diagnostic d'un diabete gestationnel.
Philips, J.-C.; SCHEEN, André ULg

in Revue Médicale de Liège (2013), 68(4), 201-7

Gestational diabetes (GD) is a common complication of pregnancy. Its prevalence depends on the strategy used for screening and the studied population. Pregnant women with GD are at increased risk for ... [more ▼]

Gestational diabetes (GD) is a common complication of pregnancy. Its prevalence depends on the strategy used for screening and the studied population. Pregnant women with GD are at increased risk for maternal and fetal complications. The relationship between maternal blood sugar and complications is linear, without a clear threshold defining GD. Therefore, the diagnostic criteria for GD have been the subject of several controversies since many years. The choice of the one-step or two-step method, the test to be used and the cut-off levels validated to define GD are still debated. The same is true regarding a universal versus a at-risk population screening. International experts have recently proposed the use of a one-step approach with a 2-hour oral glucose tolerance test for a universal screening. The need for a better harmonization regarding the diagnosis of GD is indeed mandatory. The present article discusses both the advantages and disadvantages of the various approaches used for GD screening. [less ▲]

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See detailComment je traite ... par metformine un patient diabetique avec insuffisance renale moderee.
SCHEEN, André ULg

in Revue Médicale de Liège (2013), 68(4), 190-5

Numerous patients with type 2 diabetes have renal impairment, especially in the elderly population. Metformin, the first choice oral glucose-lowering agent, is classically contraindicated in case of ... [more ▼]

Numerous patients with type 2 diabetes have renal impairment, especially in the elderly population. Metformin, the first choice oral glucose-lowering agent, is classically contraindicated in case of chronic kidney disease of stages 3-5 (creatinine clearance < 60 ml/min/1.73 m2), because of a risk of accumulation of the biguanide that may lead to lactic acidosis. Hence numerous patients with some degree of renal impairment are being treated with metformin in clinical practice, apparently without any harm. In contrast, several observational studies have shown that they may clinically benefit from this therapy, including with a significant reduction of all-cause mortality when compared to patients not receiving metformin. Thus, an increasing number of physicians plea for revisiting the official criteria of contraindication to the use of metformin in case of renal insufficiency. The present paper discusses this controversy and insists upon the mandatory cautions to be taken when using metformin in a diabetic patient with moderate (stage 3) chronic kidney disease (metformin being contraindicated in case of severe renal impairment - stages 4-5). [less ▲]

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See detailRegard sur la peau diabétique et ses méhins.
PIERARD, Gérald ULg; RADERMECKER, Régis ULg; SCHEEN, André ULg

in Revue de l'Association Belge du Diabète (2013), 56

La peau exprime certains changements qui sont souvent proportionnels à la durée et la sévérité du diabète. La plupart des composants de la peau sont affectés à des degrés divers, parfois cliniquement ... [more ▼]

La peau exprime certains changements qui sont souvent proportionnels à la durée et la sévérité du diabète. La plupart des composants de la peau sont affectés à des degrés divers, parfois cliniquement imperceptibles, parfois très sévères et invalidants. [less ▲]

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See detailThe skin landscape in diabetes mellitus. Focus on dermocosmetic management.
PIERARD, Gérald ULg; Seite, Sophie; HERMANNS, Trinh ULg et al

in Clinical, Cosmetic and Investigational Dermatology (2013), 6

BACKGROUND: Some relationships are established between diabetes mellitus (DM) and a series of cutaneous disorders. Specific dermatoses are markers for undiagnosed DM. Other disorders represent supervening ... [more ▼]

BACKGROUND: Some relationships are established between diabetes mellitus (DM) and a series of cutaneous disorders. Specific dermatoses are markers for undiagnosed DM. Other disorders represent supervening complications in an already treated DM patient. OBJECTIVE: To review the information about dermocosmetic care products and their appropriate use in the management and prevention of dermatoses related to DM. METHOD: The peer-reviewed literature and empiric findings are covered. Owing to the limited clinical evidence available for the use of dermocosmetics, a review of the routine practices and common therapies in DM-related dermatoses was conducted. RESULTS: Some DM-related dermatoses (acanthosis nigricans, pigmented purpuric dermatosis) are markers of macrovascular complications. The same disorders and some others (xerosis, Dupuytren's disease) have been found to be more frequently associated with microangiopathy. Other skin diseases (alopecia areata, vitiligo) were found to be markers of autoimmunity, particularly in type 1 DM. Unsurprisingly, using dermocosmetics and appropriate skin care has shown objective improvements of some DM-related dermatoses, such effects improve the quality of life. The most common skin manifestations of DM fall along continuum between "dry skin," xerosis, and acquired ichthyosis, occurring predominately on the shins and feet. Dermocosmetic products improve the feeling of well-being for DM patients. [less ▲]

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See detailL'Hypotension orthostatique: 1ere partie: definition, symptomatologie, evaluation et physiopathologie.
Tyberghein, Maelle; PHILIPS, Jean-Christophe ULg; Krzesinski, Jean-Marie ULg et al

in Revue Médicale de Liège (2013), 68(2), 65-73

Orthostatic hypotension (OH) is defined by a drop in arterial blood pressure (BP) of at least 20 mmHg for systolic BP and 10 mmHg for diastolic BP after standing. Symptoms are generally quite typical, but ... [more ▼]

Orthostatic hypotension (OH) is defined by a drop in arterial blood pressure (BP) of at least 20 mmHg for systolic BP and 10 mmHg for diastolic BP after standing. Symptoms are generally quite typical, but may also be rather vague. Diagnosis may be easily made by the physician in his/ her office, and confirmed, if necessary, by more sophisticated measurements. Pathophysiology is generally rather complex, but mostly involves a defect in the autonomic nervous system, in its sympathetic component. Failure of peripheral vasoconstriction seems to play a more important role than the defect in reflex tachycardia. Causes of OH are multiples. OH may occur in healthy subjects, when exposed to exceptional circumstances, but is more generally associated with various diseases, either neurological disorders or pathologies characterized by hypovolemia. Medications can also aggravate the risk of OH, among which some antihypertensive or psychotropic agents. Elderly people, especially frailty subjects, are exposed to a high risk of OH, whose origin is often multifactorial, and this complication may have serious medical consequences. [less ▲]

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