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See detailMaladie cardiovasculaire et diabète chez les personnes atteintes d'une maladie mentale sévère 2ème partie : Evaluation du risque et stratégie de prise en charge
Scheen, André ULg; Gillain, Benoit; De Hert, Marc

in Médecine des Maladies Métaboliques (2010), 4(2), 223-230

Nous avons insisté, dans un premier article, sur le fait que les personnes souffrant de maladies mentales sévères telles que la schizophrénie, la dépression ou le trouble bipolaire sont en moins bonne ... [more ▼]

Nous avons insisté, dans un premier article, sur le fait que les personnes souffrant de maladies mentales sévères telles que la schizophrénie, la dépression ou le trouble bipolaire sont en moins bonne santé physique et ont une espérance de vie moindre que la population générale. Ils sont notamment exposés à de multiples facteurs de risque métabolique et cardiovasculaire conduisant à une surmortalité coronarienne et cérébrovasculaire. Ces patients peuvent avoir un accès restreint à la médecine générale, avec des opportunités de dépistage et de prévention du risque cardiovasculaire inférieures à celles que l'on est en droit d’attendre dans une population non-psychiatrique. L'European Psychiatric Association (EPA), soutenue par l'European Association for the Study of Diabetes (EASD) et l'European Society of Cardiology (ESC), a publié récemment une déclaration de position dans le but d'améliorer la prise en charge des patients atteints de maladies mentales sévères. L'intention est d'amorcer une coopération et une prise en charge partagée entre les différents professionnels de la santé et de sensibiliser les psychiatres et les médecins de première ligne qui s'occupent de patients souffrant de maladies mentales sévères au dépistage et au traitement des facteurs de risque cardiovasculaire et du diabète. Après avoir décrit l’épidémiologie des maladies cardiovasculaires et du diabète dans la population atteinte de maladies mentales sévères et analysé l’impact des médicaments psychotropes en termes de risques métabolique et cardiovasculaire dans une première publication, le présent article décrit comment évaluer le risque de maladies cardiovasculaires et donne des conseils quant à la prise en charge des facteurs de risque cardiovasculaire et du diabète dans cette population psychiatrique. [less ▲]

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See detailMaladie cardiovasculaire et diabète chez les personnes atteintes d'une maladie mentale sévère 1ère partie : Epidémiologie et influence des médicaments psychotropes
Scheen, André ULg; Gillain, Benoit; De Hert, Marc

in Médecine des Maladies Métaboliques (2010), 4

People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess ... [more ▼]

People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed in part to an increased risk of the modifiable coronary heart disease risk factors : obesity, smoking, diabetes, hypertension and dyslipidaemia. Antipsychotic medication and possibly other psychotropic medication like antidepressants can induce weight gain or worsen other metabolic cardiovascular risk factors. Patients may have limited access to general healthcare with less opportunity for cardiovascular risk screening and prevention than would be expected in a non-psychiatric population. The European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) recently published a statement with the aim of improving the care of patients suffering from severe mental illness. This first paper summarizes the epidemiological data of coronary heart disease and stroke in this special population as well as the potential cardiometabolic consequences of psychotropic medications. A second article will explain how to evaluate the cardiovascular risk and give recommendations concerning the appropriate management of risk factors and diabetes in the psychiatric population. [less ▲]

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See detailTraitements neuroleptiques et troubles métaboliques
Scheen, André ULg; van Winkel, R.; De Hert, Marc

in Médecine des Maladies Métaboliques (2008), 2(6), 593-599

Les neuroleptiques, en particulier les antipsychotiques atypiques ou de seconde génération, sont associés à des troubles métaboliques dont un gain pondéral, parfois majeur, un syndrome métabolique et la ... [more ▼]

Les neuroleptiques, en particulier les antipsychotiques atypiques ou de seconde génération, sont associés à des troubles métaboliques dont un gain pondéral, parfois majeur, un syndrome métabolique et la survenue (ou l’aggravation) d’un diabète sucré. Outre la survenue, assez fréquente, d’une diminution de tolérance au glucose ou d’un diabète (généralement dans un contexte de syndrome métabolique) chez des sujets présentant, par ailleurs, les facteurs de risque habituel de diabète de type 2, de rares cas de décompensations métaboliques aiguës avec acidocétose sévère et/ou pancréatite aiguë, allant jusqu’au décès, ont été rapportés. Le risque métabolique paraît différent selon les molécules considérées et non nécessairement lié à la prise pondérale. Une surveillance métabolique attentive et des conseils hygiéno-diététiques, sont recommandés chez tout patient sous antipsychotiques atypiques. Éventuellement, une intervention pharmacologique pourra être envisagée. Enfin, le choix du neuroleptique le plus approprié devrait être influencé, non seulement par son efficacité sur le plan psychiatrique, mais aussi par le profil de risque métabolique du patient et de l’antipsychotique. [less ▲]

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See detailPrevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder.
van Winkel, Ruud; De Hert, Marc; Van Eyck, Dominique et al

in Bipolar Disorders (2008), 10(2), 342-8

OBJECTIVES: The presence of metabolic abnormalities is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of the metabolic abnormalities in ... [more ▼]

OBJECTIVES: The presence of metabolic abnormalities is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of the metabolic abnormalities in disorders other than schizophrenia in which antipsychotic medication is part of routine treatment. METHODS: Sixty consecutive patients with bipolar disorder (BD) at our university psychiatric hospital and affiliate services were entered in an extensive prospective metabolic study including an oral glucose tolerance test. The prevalence of the metabolic syndrome was assessed based on the National Cholesterol Education Program Adult Treatment Protocol (ATP-III) criteria, the adapted ATP-III criteria using a fasting glucose threshold of 100 mg/dL, and the recently proposed criteria from the International Diabetes Federation (IDF). RESULTS: The analysis of 60 patients showed a prevalence of the metabolic syndrome of 16.7% (ATP-III), 18.3% (adapted ATP-III) and 30.0% (IDF), respectively. A total of 6.7% of the patients met criteria for diabetes and 23.3% for pre-diabetic abnormalities. CONCLUSIONS: The metabolic syndrome and glucose abnormalities are highly prevalent among patients with BD. They represent an important risk for cardiovascular and metabolic disorders. Assessment of the presence and monitoring of metabolic abnormalities and its associated risks should be part of the clinical management of patients with BD. [less ▲]

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See detailA cross-sectional evaluation of adiponectin plasma levels in patients with schizophrenia and schizoaffective disorder.
Hanssens, Linda; van Winkel, Ruud; Wampers, Martien et al

in Schizophrenia Research (2008), 106(2-3), 308-14

BACKGROUND: In recent years, several studies showed increased rates of hyperglycaemia, diabetes, dyslipidemia, metabolic syndrome as well as cardiovascular disease in schizophrenic patients. The ... [more ▼]

BACKGROUND: In recent years, several studies showed increased rates of hyperglycaemia, diabetes, dyslipidemia, metabolic syndrome as well as cardiovascular disease in schizophrenic patients. The underlying mechanism, however, is poorly understood. Adiponectin is a recently identified adipocyte-derived protein, with low adiponectin levels being associated with metabolic abnormalities such as obesity, insulin resistance and type 2 diabetes. METHODS: Fasting adiponectin levels were assessed in a cross-sectional sample of 386 patients with schizophrenia or schizoaffective disorder. All patients were on monotherapy of second-generation antipsychotics (SGA) and underwent an extensive metabolic screening including an oral glucose tolerance test (OGTT). RESULTS: Adiponectin plasma levels were inversely correlated with BMI, and differed significantly between patients with normal weight, overweight or obesity (p<0.05). Patients who met criteria for the metabolic syndrome, according to adapted National Cholesterol Educational Program - Adult Treatment Panel criteria (NCEP-ATP III) (29.3%), had significantly lower adiponectin levels than patients not meeting metabolic syndrome criteria (p<0.0001). Patients without glucose abnormalities (78%) had significantly higher adiponectin levels than patients with diabetes (5.7%) (p<0.05). After controlling for components of metabolic syndrome and sex, antipsychotic medication independently influenced adiponectin levels (p<0.0001), with the lowest mean levels in patients on clozapine and olanzapine. CONCLUSIONS: Adiponectin levels in schizophrenic patients mirror what is observed in the general population, with the lowest levels in the most metabolically comprised subjects. However, antipsychotic medication may also influence adiponectin regulation independently, a finding that should be confirmed in longitudinal studies. [less ▲]

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See detailTypical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review.
De Hert, Marc; Schreurs, Vincent; Sweers, Kim et al

in Schizophrenia Research (2008), 101(1-3), 295-303

The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the ... [more ▼]

The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the onset of the disorder and specifically no data on patients treated in the era when only first-generation antipsychotics were available. METHODS: Data from a historic cohort of consecutively admitted first-episode patients with schizophrenia treated with first-generation antipsychotics (FGAs) were compared with an age and sex matched series of consecutive first-episode patients treated only with second-generation antipsychotics (SGAs). Rates of MetS were compared at baseline and after on average 3 years of treatment exposure. RESULTS: At first episode there was no difference in the prevalence of MetS between the historic and the current cohort. Rates of MetS increased over time in both groups, but patients started on SGAs had a three times higher incidence rate of MetS (Odds Ratio 3.6, CI 1.7-7.5). The average increase in weight and body mass index was twice as high in patients started on SGA. The difference between the FGA and SGA group was no longer significant when patients started on clozapine and olanzapine were excluded. CONCLUSION: Rates of MetS at the first episode of schizophrenia today are not different from those of patients 15 to 20 years ago. This finding counters the notion that the high rates of metabolic abnormalities in patients with schizophrenia currently reported are mainly due to lifestyle changes over time in the general population. Some SGAs have a significantly more negative impact on the incidence of MetS compared to FGAs in first-episode patients. [less ▲]

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See detailMajor changes in glucose metabolism, including new-onset diabetes, within 3 months after initiation of or switch to atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder.
van Winkel, Ruud; De Hert, Marc; Wampers, Martien et al

in Journal of Clinical Psychiatry (2008), 69(3), 472-9

OBJECTIVE: To investigate 3-month changes in glucose metabolism in a naturalistic sample of patients with schizophrenia newly started on or switched to specific atypical antipsychotic medication therapy ... [more ▼]

OBJECTIVE: To investigate 3-month changes in glucose metabolism in a naturalistic sample of patients with schizophrenia newly started on or switched to specific atypical antipsychotic medication therapy. METHOD: One hundred eighty-three patients were evaluated before initiation and 3 months after with a 75-g glucose load oral glucose tolerance test (OGTT). Data were collected between November 2003 and January 2007. RESULTS: Eight patients (4.4%) developed new-onset diabetes within 3 months. Initiation of clozapine resulted in a significantly higher risk for new-onset glucose abnormalities than initiation of aripiprazole (odds ratio = 67.29, 95% CI = 5.23 to 866.49). Significant drug x time interactions were found for all OGTT glucose assessments (fasting: F = 6.79, df = 5,177; p < .0001; 30 minutes: F = 3.89, df = 5,177; p = .0023; 60 minutes: F = 5.03, df = 5,177; p = .0002; 120 minutes: F = 3.78, df = 5,177; p = .0028), with the evolution of plasma glucose levels being significantly worse in patients initiated on clozapine therapy (fasting, 30 minutes, and 60 minutes), olanzapine therapy (fasting, 60 minutes, and 120 minutes), and quetiapine therapy (fasting and 60 minutes) than in patients initiated on aripiprazole therapy (p < .05). Clozapine was also significantly more deleterious than risperidone and amisulpride for fasting plasma glucose level changes (p < .05). Type of initiation (start or switch) did not affect any of the metabolic parameters. CONCLUSIONS: The incidence of new-onset glucose abnormalities, including diabetes, in the first 3 months after newly starting or switching atypical antipsychotic medication is high and may be markedly influenced by type of prescribed antipsychotic. The importance of accurately screening for new-onset glucose abnormalities after initiation of an atypical antipsychotic is emphasized. [less ▲]

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See detailPsychiatric diagnosis as an independent risk factor for metabolic disturbances: results from a comprehensive, naturalistic screening program.
van Winkel, Ruud; van Os, Jim; Celic, Ivan et al

in Journal of Clinical Psychiatry (2008), 69(8), 1319-27

OBJECTIVE: Unconfounded differences in inherent vulnerability to metabolic disturbance may be hypothesized for different diagnostic groups with severe mental illness. METHOD: A naturalistic cohort of ... [more ▼]

OBJECTIVE: Unconfounded differences in inherent vulnerability to metabolic disturbance may be hypothesized for different diagnostic groups with severe mental illness. METHOD: A naturalistic cohort of patients diagnosed with DSM-IV bipolar disorder (N = 112), schizophrenia (N = 503), and schizoaffective disorder (N = 92) were assessed for metabolic disturbances. The prospective inclusions started in November 2003 and were concluded in July 2007. RESULTS: Diagnosis was strongly associated with the metabolic syndrome (chi(2) = 14.90, df = 2, p < .001). Compared with bipolar patients, the unadjusted risk for metabolic syndrome was significantly higher for schizoaffective (odds ratio [OR] = 3.51, p < .0001) but not for schizophrenia patients (OR = 1.58, p = .094). Differences were not reducible to confounding factors including treatment. Rather, the difference between bipolar and schizophrenia patients also reached significance after adjustment (OR = 1.97, p = .046). Furthermore, the association between diagnosis and glucose dysregulation was significant (chi(2) = 6.97, df = 2, p = .031), with a significantly higher risk in schizoaffective (unadjusted OR = 2.12, p = .022) but not in schizophrenia patients (unadjusted OR = 1.13, p = .640) compared with bipolar patients. Diagnostic differences in glucose dysregulation were in part mediated by body mass index (BMI). CONCLUSIONS: Schizoaffective patients in particular may be at risk for metabolic disturbances compared with bipolar and schizophrenia patients. Differences were not reducible to known metabolic risk factors and could only be explained in part by higher BMI in schizoaffective patients, suggesting an increased inherent vulnerability in this group. [less ▲]

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See detailOral glucose tolerance tests in treated patients with schizophrenia. Data to support an adaptation of the proposed guidelines for monitoring of patients on second generation antipsychotics?
De Hert, Marc; Van Eyck, Dominique; Hanssens, Linda et al

in European Psychiatry (2006), 21(4), 224-226

Objective. - A recent consensus conference has proposed guidelines for the monitoring for diabetes in patients with schizophrenia and also identifies the need of long-term prospective studies. Method. - A ... [more ▼]

Objective. - A recent consensus conference has proposed guidelines for the monitoring for diabetes in patients with schizophrenia and also identifies the need of long-term prospective studies. Method. - A large scale prospective study on metabolic risks of antipsychotic medication is currently ongoing. At baseline, patients get a full laboratory screening, ECG and an oral glucose tolerance test (OGTT). Baseline data on 100 non-diabetic patients at study inclusion and stable on medication for at least 6 months are presented. Results. - Glucose abnormalities are found in 22% of patients at baseline, A monitoring protocol based only on fasting glucose would not have detected 63.6% of these patients with classifiable glucose abnormalities in our sample. Fasting insulin and measures for insulin resistance have a high predictive value for abnormalities late in the OGTT. Conclusion. - Already at baseline, metabolic problems are frequently present in patients with schizophrenia treated with antipsychotics. Adding assessment of fasting insulin in a monitoring protocol improves detection of glucose abnormalities late in an OGTT. (c) 2005 Elsevier SAS. All rights reserved. [less ▲]

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See detailScreening for diabetes and other metabolic abnormalities in patients with schizophrenia and schizoaffective disorder: evaluation of incidence and screening methods.
van Winkel, Ruud; De Hert, Marc; Van Eyck, Dominique et al

in Journal of Clinical Psychiatry (2006), 67(10), 1493-500

OBJECTIVE: To assess the diagnostic properties of 2 different screening guidelines for the detection of diabetes in patients diagnosed with schizophrenia. METHOD: Over a 2-year period (November 2003 ... [more ▼]

OBJECTIVE: To assess the diagnostic properties of 2 different screening guidelines for the detection of diabetes in patients diagnosed with schizophrenia. METHOD: Over a 2-year period (November 2003-November 2005), 415 patients with schizophrenia were screened with a full laboratory screening and a 75-g oral glucose tolerance test (OGTT). The sensitivity of 2 screening strategies was compared with the "gold standard": the OGTT. The 2 strategies were (1) assessing fasting glucose in all patients, as suggested by the American Psychiatric Association/ American Diabetes Association (APA/ADA), and (2) a screening strategy derived from the guidelines of the World Health Organization of assessing fasting glucose in all patients (step 1) and subsequently performing an OGTT in patients with impaired fasting glucose (step 2). RESULTS: Of the total sample, 6.3% (N = 26) met criteria for diabetes, resulting in a mean annual incidence of diabetes of 3.15% (6.3% incident cases/2 years). A screening based on the APA/ADA guidelines detected diabetes in 12 (46.2%) of the 26 cases identified by the OGTT. The proposed 2-step strategy detected 25 (96.2%) of 26 cases. CONCLUSION: The data suggest a high incidence of diabetes in patients diagnosed with schizophrenia. However, the guidelines to detect diabetes as proposed by the APA/ADA did not sufficiently detect diabetes in this specific high-risk group. The alternative 2-step strategy was able to detect the vast majority of diabetes cases and should therefore be considered in the clinical routine of screening and monitoring patients with schizophrenia. [less ▲]

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See detailUsefulness of glycosylated haemoglobin (HbA1c) to screen for diabetes in patients with schizophrenia.
Hanssens, Linda; De Hert, Marc; Van Eyck, Dominique et al

in Schizophrenia Research (2006), 85(1-3), 296-7

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See detailTreatment with rosuvastatin for severe dyslipidemia in patients with schizophrenia and schizoaffective disorder.
De Hert, Marc; Kalnicka, Dita; van Winkel, Ruud et al

in Journal of Clinical Psychiatry (2006), 67(12), 1889-96

BACKGROUND: Mortality rates in patients with schizophrenia are double compared to those in the general population, with cardiovascular disease causing 50% of the excess. Lowering low-density lipoprotein ... [more ▼]

BACKGROUND: Mortality rates in patients with schizophrenia are double compared to those in the general population, with cardiovascular disease causing 50% of the excess. Lowering low-density lipoprotein (LDL) cholesterol is recognized as a primary target for the prevention of cardiovascular mortality according to the National Cholesterol Education Program-Adult Treatment Panel III. Use of lipid-lowering drugs such as statins is recommended when lifestyle changes are not sufficient to reach the LDL goal. The efficacy and safety of rosuvastatin treatment were evaluated in schizophrenic patients. METHOD: 100 schizophrenic patients with severe dyslipidemia were identified. All were treated with antipsychotics. Fifty-two patients were treated with rosuvastatin and compared with 48 who did not receive statin treatment. All patients were screened for cardiovascular risk factors and examined at baseline. The effects of lipid-lowering medication on lipid profile, glucose homeostasis, and components of metabolic syndrome were evaluated at 3-month follow-up. The study began in 2003, and all data available until December 2005 are reported. RESULTS: After 3 months of statin therapy, a significant decrease in triglycerides, total cholesterol, LDL cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol and in associated ratios (LDL/HDL, total cholesterol/HDL) was observed. The difference was highly significant compared to patients not receiving statin treatment. No significant changes occurred in HDL cholesterol, body mass index and waist circumference, or glucose homeostasis. The only component of metabolic syndrome affected by statin therapy was the serum triglyceride level. CONCLUSION: Rosuvastatin proved effective in the management of dyslipidemia in patients with schizophrenia treated with antipsychotics. More complex treatment may be required for associated metabolic disturbances. [less ▲]

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See detailOral glucose tolerance tests in schizophrenic patients treated with antipsychotics
De Hert, Marc; Van Eyck, Dominique; Hermans, Gilberte ULg et al

in International Journal of Neuropsychopharmacology (2004, June), 7(Suppl. 1), 424

Objective. –A recent consensus conference has proposed guidelines for the monitoring for diabetes in patients with schizophrenia and also identifies the need of long-term prospective studies. Method. – A ... [more ▼]

Objective. –A recent consensus conference has proposed guidelines for the monitoring for diabetes in patients with schizophrenia and also identifies the need of long-term prospective studies. Method. – A large scale prospective study on metabolic risks of antipsychotic medication is currently ongoing. At baseline, patients get a full laboratory screening, ECG and an oral glucose tolerance test (OGTT). Baseline data on 100 non-diabetic patients at study inclusion and stable on medication for at least 6 months are presented. Results. – Glucose abnormalities are found in 22% of patients at baseline.A monitoring protocol based only on fasting glucose would not have detected 63.6% of these patients with classifiable glucose abnormalities in our sample. Fasting insulin and measures for insulin resistance have a high predictive value for abnormalities late in the OGTT. Conclusion. – Already at baseline, metabolic problems are frequently present in patients with schizophrenia treated with antipsychotics. Adding assessment of fasting insulin in a monitoring protocol improves detection of glucose abnormalities late in an OGTT. [less ▲]

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