Evaluación de síndrome metabólico en varones hospitalizados en Unidad de Corta Estadía Psiquiátrica Marzo 2017 / Evaluation of metabolic syndrome in Hospitalized Men in the Short Stay Psychiatric Unit. March 2017

El síndrome metabólico (SM) corresponde a un conjunto de factores de riesgo derivados de la obesidad visceral e insulinoresistencia. 35.3% de la población adulta chilena presentó SM en el período 2009 - 2010, con diferencia significativa entre hombres y mujeres (41.6% vs 30.9%, respectivamente). En Estados Unidos se ha calculado que la media de años potencialmente perdidos en pacientes con enfermedades mentales va de 25 a 30, comparada con la población general. La principal causa de muerte es la enfermedad coronaria. La mayoría de los pacientes en tratamiento neuroléptico en hospitales psiquiátricos no reciben control de factores de riesgo metabólicos. La evidencia señala que los pacientes esquizofrénicos no son adecuadamente pesquisados ni tratados por Dislipidemia (hasta un 88% de estos pacientes siguen sin tratamiento) ni por hipertensión (hasta un 62%). El objetivo de este trabajo es evaluar factores de riesgo cardiovascular en varones hospitalizados en unidad de corta estadía psiquiátrica del Instituto Psiquiátrico Dr. José Horwitz Barak. Se evaluó a 35 pacientes varones, de los cuales un 37% presentó SM, un 45.3% presentó sobrepeso.

The metabolic syndrome (MS) corresponds to a set of risk factors derived from visceral obesity and insulin resistance. 35.3% of the Chilean adult population had MS in the 2009-2010 period, with a significant difference between men and women (41.6% vs 30.9%, respectively). In the United States, it has been estimated that the average number of years potentially lost in patients with mental illness ranges from 25 to 30, compared with the general population. The main cause of death is coronary heart disease. Most patients on neuroleptic treatment in psychiatric hospitals do not receive control of metabolic risk factors. The evidence indicates that schizophrenic patients are not adequately researched or treated for dyslipidemia (up to 88% of these patients remain untreated) or hypertension (up to 62%). OBJECTIVE: To evaluate cardiovascular risk factors in hospitalized men in a short stay psychiatric unit of the Psychiatric Institute Dr. José Horwitz Barak. Thirty-five male patients were evaluated, of which 37% had MS, and 45.3% were overweight.

Prevalência de síndrome metabólica em pacientes com esquizofrenia refratária / Metabolic syndrome prevalence in patients with refractory schizophrenia / Prevalencia de síndrome metabólico en pacientes con esquizofrenia refractaria

RESUMO Objetivo: Estimar prevalência de síndrome metabólica (SM) e seus fatores associados em pacientes com es quizofrenia refratária em uso do antipsicótico clozapina. Método: Trata-se de um estudo descritivo e trans versal, realizado na Região Ampliada Oeste do Estado de Minas Gerais (MG), em 2015, com uma amostra de 72 pacientes. Foram coletados dados sociodemográficos, clínicos, antropométricos e bioquímicos. Realizou-se análise descritiva, univariada e multivariada. Resultados: Observou-se prevalência de SM em 47,2% da amos tra, com predomínio entre as mulheres (58,8%). Pacientes com SM apresentaram percentuais mais elevados de alterações, principalmente em relação à glicemia e triglicérides. O uso de quatro ou mais medicamentos e a presença de sobrepeso e obesidade estiveram associados à SM. Além disso, pacientes com a síndrome apresen taram um histórico de menos internações psiquiátricas, comparados àqueles que não a possui. Conclusão: A prevalência de SM encontrada nos pacientes com esquizofrenia refratária foi elevada e alarmante. A presença de sobrepeso e obesidade e o uso de 4 ou mais medicamentos podem estar associados com o desenvolvimento de SM neste grupo. Essa taxa pode representar um importante indicador de risco cardiovascular, sendo sugerida a construção de estratégias de prevenção primária das alterações metabólicas, bem como se indica que o paciente seja acompanhado periodicamente, principalmente em relação aos componentes da SM.

ABSTRACT Objective: To estimate the prevalence of the metabolic syndrome (MS) and its associated factors in patients with refractory schizophrenia using the antipsychotic clozapine. Method: This is a descriptive cross-sectional study conducted in the extended western region of Minas Gerais (MG), Brazil, in 2015, using a sample of 72 patients. We collected sociodemographic, clinical, anthropometric and biochemical data and conducted descriptive univariate and multivariate analysis. Results: We verified the prevalence of MS in 47.2% of the sample, with a greater predominance among women (58.8%). Patients with MS showed higher change values, especially in relation to blood glucose and triglycerides. The use of four or more medications and the presence of overweight and obesity were associated with MS. In addition, patients with the syndrome had fewer cases of psychiatric hospitalizations than those who did not have it. Conclusion: High and alarming levels of MS prevalence were found in patients with refractory schizophrenia. The presence of overweight and obesity and the use of 4 or more medications may be associated with the development of the MS in this group. These levels could represent an important indicator of cardiovascular risk, which raises the need to develop strategies for primary prevention of metabolic alterations, and highlights the importance of a periodical monitoring of the patient, especially regarding the components of the MS.

RESUMEN Objetivo: Estimar la prevalencia del síndrome metabólico (SM) y sus factores asociados en pacientes con es quizofrenia refractaria que utilizan clozapina como antipsicótico. Material y método: Se trata de un estudio descriptivo y transversal realizado en la región ampliada del oeste de Minas Gerais (MG) en 2015, con una muestra de 72 pacientes. Se recogieron datos sociodemográficos, clínicos, antropométricos y bioquímicos. Se realizó análisis descriptivo, univariado y multivariado. Resultados: Se observó prevalencia de SM en el 47,2% de la muestra, con una prevalencia entre las mujeres (58,8%). Los pacientes con SM tenían mayores porcenta jes de alteración, especialmente en la glucosa en sangre y triglicéridos. El uso de cuatro o más medicamentos y la presencia de sobrepeso y obesidad se asociaron con SM. Además, los pacientes con el síndrome tenían un historico de hospitalizaciones psiquiátricas menor que los que no lo tienen. Conclusión: La prevalencia del SM encontrado en pacientes con esquizofrenia refractaria fue alto y alarmante. La presencia de sobrepeso y obesidad, y el uso de 4 o más fármacos puede estar asociado con el desarrollo de la SM en este grupo. Esta tasa puede representar un importante indicador de riesgo cardiovascular, y sugiere la construcción de estrategias de prevención primaria de los cambios metabólicos, así como que el paciente debe controlarse periódicamente, especialmente en relación con los componentes del SM.

Efecto preventivo del extracto etanólico de las hojas de Annona muricata L. (guanábana) sobre el síndrome metabólico inducido en ratas / Preventive effect of the ethanol extract of the leaves of Annona muricata L. (soursop) on the metabolic syndrome induced in rats

Introducción: Annona muricata L. (Guanábana), planta medicinal con diversos beneficios terapéuticos. Objetivos: Evaluar el efecto preventivo del extracto etanólico de hojas de guanábana (EEA) administrado en ratas con síndrome metabólico. Diseño: Experimental, Pre-clínico, "In vivo". Lugar: Laboratorio de Farmacología Experimental, Facultad de Medicina Humana-UNMSM, Lima, Perú. Material biológico: Hojas de guanábana, ratas machos de 2 meses, cepa Holtzmann de 175±25g. Intervenciones: La mezcla de colesterol 200mg/kg y fructosa 1000 mg/día (CF) indujo la patología concomitantemente se administró (EEA) por un periodo de 90 días. Noventa animales fueron divididos en nueve grupos: 1) normal (SSF 2mL/kg); 2) EEA 200mg/kg; 3) CF 200mg/kg; 4- 6) CF + EEA 50, 100 y 200mg/kg respectivamente; 7) CF + atorvastatina 20mg/kg; 8) CF + enalapril 20mg/kg; 9) CF + enalapril 20mg/kg + atorvastatina 20mg/kg. Principales medidas de resultado: peso corporal (g), niveles de glicemia (mg/dL), presión arterial (mmHg) y colesterol (mg/dL). Resultados: Hubo mejor disminución del peso corporal en 10.2 por ciento; glicemia y HbA1c en 21.5 por ciento en ambas a 200mg/kg (p<0.0001); disminuyo la presión sistólica (35.7 por ciento), diastólica (34.9 por ciento) y media (37 por ciento) a 100mg/kg (p<0.0001); el colesterol bajo (35.4 por ciento) y el HDL aumento (28.7 por ciento) ambos con 100mg/kg (p<0.0001). Conclusiones: El extracto etanólico de las hojas de Annona muricata L. (Guanábana) mostro el efecto preventivo del síndrome metabólico inducido en ratas por colesterol más fructosa.

Introduction: Annona muricata L (Soursop) is a medicinal plant that is attributed many therapeutic benefits. Objective: To evaluate preventive effect of ethanolic extract from leaves of soursop (EEA) administered in rats with metabolic syndrome. Design: Experimental, Pre-clinic, "in vivo". Setting: Laboratory of Experimental Pharmacology, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological Material: Soursop leaves, male rats of two months, Holtzman strain of 175 ± 25g. Interventions: The mixture cholesterol 200 mg/kg and fructose 1000mg/day (CF) induced pathology was co-administered (EEA) for 90 days. Ninety animals were divided into nine groups: 1) normal (SSF 2mL/kg); 2) EEA 200mg/kg; 3) CF 200mg/kg; 4-6) CF + EEA 50, 100 y 200mg/kg respectively; 7) CF + atorvastatin 20mg/kg; 8) CF + enalapril 20mg/kg; 9) CF + enalapril 20mg/kg + atorvastatin 20 mg/kg. Main outcome measures: body weight (g), glycemic levels (mg/dL), blood pressure (mmHg) and cholesterol (mg/dL). Results: There was better decrease of body weight in 10.2 per cent; blood glucose and HbA1c in 21.5 per cent both 200mg/kg (p<0.0001); decreased systolic blood pressure (35.7 per cent), diastolic (34.9 per cent) and medium (37 per cent) to 100mg/kg (p<0.0001); low cholesterol (35.4 per cent) and; increase HDL (28.7 per cent) both with 100mg/kg (p<0.0001). Conclusions: The ethanolic extract of the leaves of A. muricata L (soursop) showed the preventive effect in rats developing the metabolic syndrome in rats induced by fructose more cholesterol.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet

BACKGROUND: Metabolic syndrome is a growing worldwide health problem. We evaluated the effects of wine grape powder (WGP), rich in antioxidants and fiber, in a rat model of metabolic syndrome induced by a high fructose diet. We tested whether WGP supplementation may prevent glucose intolerance and decrease oxidative stress in rats fed with a high fructose diet. METHODS: Male Sprague-Dawley rats weighing 180 g were divided into four groups according to their feeding protocols. Rats were fed with control diet (C), control plus 20 % WGP (C + WGP), 50 % high fructose (HF) or 50 % fructose plus 20 % WGP (HF + WGP) for 16 weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood pressure were measured. Homeostasis model assessment (HOMA) index was calculated using insulin and glucose values. A glucose tolerance test was performed 2 days before the end of the experiment. As an index of oxidative stress, thio-barbituric acid reactive substances (TBARS) level was measured in plasma and kidney, and superoxide dismutase was measured in the kidney. RESULTS: Thiobarbituric acid reactive substances in plasma and renal tissue were significantly higher when compared to the control group. In addition, the area under the curve of the glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood glucose, plasma insulin levels, and the HOMA index, were also increased. WGP supplementation prevented these alterations in rats fed with the HF diet. We did not find any significant difference in body weight or systolic blood pressure in any of the groups. CONCLUSIONS: Our results show that WGP supplementation prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats fed with HF diet. We propose that WGP may be used as a supplement in human food as well.

Glycyrrhizin ameliorates insulin resistance, hyperglycemia, dyslipidemia and oxidative stress in fructose-induced metabolic syndrome-X in rat model.

This study investigates if glycyrrhizin, a constituent of licorice (Glycyrrhiza glabra) root, is able to treat the complications (insulin resistance, hyperglycemia, dyslipidemia and oxidative stress) of metabolic syndrome. Metabolic syndrome was induced in rats by feeding a fructose-enriched (60%) diet for six weeks, after which single dose of glycyrrhizin (50 mg/kg body weight) was administered intraperitoneally. Different biochemical parameters from blood were estimated during three weeks after treatment. Then the rats were sacrificed to collect skeletal muscle tissue. Glycyrrhizin reduced the enhanced levels of blood glucose, insulin and lipids in metabolic syndrome group. Increased advanced glycation end products of hemoglobin, glycohemoglobin, hemoglobin-mediated iron release and iron-mediated free radical reactions (arachidonic acid and deoxyribose degradation) in metabolic syndrome were inhibited by glycyrrhizin treatment. Reduced activities of enzymatic antioxidants (superoxide dismutase and catalase) and elevated oxidative stress markers (malonaldehyde, fructosamine, hemoglobin carbonyl content and DNA damage) in metabolic syndrome were reversed to almost normal levels by glycyrrhizin. The decreased levels of peroxisome proliferator activated receptor (PPAR) and glucose transporter 4 (GLUT4) proteins in skeletal muscle of metabolic syndrome group were elevated by glycyrrhizin, indicating improved fatty acid oxidation and glucose homeostasis.

Antidiabetic effect of hydroalcholic Urtica dioica leaf extract in male rats with fructose- induced insulin resistance

Urtica dioica has been used as antihypertensive, antihyperlipidemic and antidiabetic herbal medicine. The purpose of this study was to study the effect of hydroalcoholic extract of Urtica dioica on fructose-induced insulin resistance rats. Forty male Wistar rats were randomly divided into five groups including control, fructose, extract 50, extract 100 and extract 200. The control rat received vehicle, the fructose and extract groups received fructose 10% for eight weeks. The extract groups received single daily injection of vehicle, 50, 100 or 200 mg/kg/day for the two weeks. Blood glucose, insulin, last fasting insulin resistance index [FIRI], serum triglyceride [TG], low-density lipoprotein [LDL], very low-density lipoprotein [VLDL], high-density lipoprotein [HDL], alanin trasaminase [AST] and alkaline phosphatase [ALP], leptin and LDL/HDL ratio were determined. Compared to control group, daily administration of fructose was associated with significant increase in FIRI, blood glucose and insulin, significant decrease in lepin, and no significant change in TG, HDL, LDL, LDL/HDL ratio, VLDL, ALT, and ALP. The extract significantly decreased serum glucose, insulin, LDL and leptin, and LDL/HDL ratio and FIRI. It also significantly increased serum TG, VLDL, and AST, but did not change serum ALP. We suggest that Urtica dioica extract, by decreasing serum glucose, and FIRI, may be useful to improve type 2 diabetes mellitus. Also, by positive effect on lipid profile and by decreasing effect on leptin, it may improve metabolic syndrome

La inactividad física en etapas tempranas del desarrollo disminuye la expresión de Akt en el músculo sóleo de ratas / Akt expression is diminished by physical inactivity in early stages of development in soleus muscle of rats

El Síndrome Metabólico corresponde a una serie de trastornos relacionados con obesidad e inactividad física. Poco se conoce respecto de la falta de ejercicio, en estadios tempranos del desarrollo, en la susceptibilidad a un fenotipo insulinoresistente inducido por una dieta alta en grasas. Akt juega un rol clave en la síntesis de proteínas y el transporte de glucosa en el músculo esquelético y ha mostrado ser regulada por la actividad muscular. El objetivo del presente estudio fue determinar el efecto de la inactividad física temprana sobre el crecimiento muscular y la susceptibilidad de adquirir un fenotipo diabético y evaluar su relación con la expresión de Akt. Cuarenta ratas Wistar fueron distribuidas en 2 grupos (Grupos Control, Std) y Restricción de movimiento (RM). Entre los días postnatal 23 y 70 los animales del grupo RM fueron alojados en pequeñas jaulas que no permitían una actividad motora relevante. A partir del día postnatal 71 y hasta el día 102, 10 ratas de cada grupo fueron alimentadas con una Dieta Alta en Grasas (RM-DAG y Std-DAG). No se observaron diferencias en el peso corporal total pero DAG generó un significativo incremento en la grasa epididimal. RM generó una disminución significativa en el peso de los músculos sóleo. La captación de glucosa estimulada por insulina fue menor en el grupo RM-DAG. Los niveles de proteína Akt fueron menores en los grupos RM. El análisis de PCR a tiempo real mostró que la restricción de movimiento disminuyó los niveles de ARNm de AKT1 en el músculo sóleo, independiente de la dieta administrada. Estos hallazgos sugieren que la inactividad física temprana limita el crecimiento muscular y contribuye en la instauración un fenotipo insulino resistente, lo cual puede ser en parte explicado por una desregulación en la expresión de Akt.

Metabolic Syndrome is a group of conditions related to obesity and physical inactivity. Little is known about the role of physical inactivity, in early stages of development, in the susceptibility to insulin resistant phenotype induced by high fat diet. Akt plays a key role in protein synthesis and glucose transport in skeletal muscle and has been regulated by muscle activity. The objective of present study was to determine the effect of early physical inactivity on muscle growth and susceptibility to acquire a diabetic phenotype and to assess its relationship with Akt expression. Forty Wistar male rats were distributed in two groups (standard group, Std) and movement restriction (RM). Between days 23 and 70 after birth, RM group was kept in small cages that did not allow them to perform relevant motor activity. From day 71 to 102 after birth, 10 rats of each group were fed with hyperlipidic diet (groups Std-DAG and RM-DAG). No differences were observed in total body weight although DAG increased epididymal fat pad weight. RM decreased significantly the soleus weight. Insulin-mediated glucose uptake was lower in RM-DAG group. Akt protein levels were lower in RM groups. Real time RT-PCR analysis showed that movement restriction decreased mRNA levels of AKT1 in soleus muscle, regardless of supplied diet. These findings suggest that early physical inactivity limits muscle's growth and contributes to instauration of insulin resistant phenotype, which can be partly explained by dysregulation of Akt expression.

Metabolic syndrome in HIV-infected patients receiving antiretroviral therapy in Latin America

OBJECTIVE: To evaluate the prevalence of and the associated factors for metabolic syndrome (MS) among Latin American HIV-infected patients receiving antiretroviral therapy (ART) using baseline data from the RAPID II study. METHODS: A longitudinal study to evaluate the metabolic profile, cardiovascular disease (CVD) risk and associated treatment practices to reduce this risk has been conducted in seven Latin American countries (the RAPID II study). Adult HIV patients with at least six months of RT were enrolled. MS was defined following ATP-III criteria. Demographic and anthropometric data, serum biochemical and clinical parameters were compared in patients with and without MS using bivariate and multivariate analysis. RESULTS: A total of 4,010 patients were enrolled, 2,963 (74 percent) were males. Mean age (SD) was 41.9 (10.0) years. The prevalence of MS was 20.2 percent. Females had higher prevalence of MS than males (22.7 percent vs. 19.4 percent, p = 0.02). MS was driven by high triglycerides, low HDL-cholesterol and high blood pressure (HBP). Patients with MS had higher 10year CVD risk: 22.2 percent vs. 7.4 percent, p < 0.001. Age (OR: 1.05 per year), female gender (OR: 1.29), family history of CVD (OR: 1.28), CD4 cell count (OR: 1.09 per 100 cell increase), and protease inhibitor based-ART (OR: 1.33) correlated with MS in the multivariate analysis. CONCLUSIONS: Prevalence of MS in this setting was similar to that reported from developed countries. MS was driven by high triglycerides, low-HDL and HBP, and it was associated with higher risk of CVD. Traditional risk factors, female gender, immune reconstitution, and protease inhibitor based-ART correlated with MS.

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART

OBJECTIVE: Determine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART). METHODS: A cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis. RESULTS: A total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44 percent received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2 percent and 20.2 percent, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females. CONCLUSIONS: Traditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.

Fructose and cardiometabolic disorders: the controversy will, and must, continue: [review]

The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit. Nevertheless major caveats exist (species, gender, source of fructose, study protocols) which are detailed in this review and presently prevent any firm conclusion. New studies taking into account these confounding factors should be undertaken in order to ascertain whether or not high fructose diet is harmful.

Exercício físico previne alterações cardiometabólicas induzidas pelo uso crônico de glicocorticóides / Exercise prevents cardiometabolic alterations induced by chronic use of glucocorticoids

FUNDAMENTO: Cronicamente, os glicocorticóides induzem alterações cardiometabólicas adversas, incluindo resistência à insulina, diabete, dislipidemia, esteatose hepática e hipertensão arterial. OBJETIVOS: Avaliar o efeito da prática regular de exercício físico aeróbio sobre as alterações cardiometabólicas induzidas por administração crônica de dexametasona (Dex - 0,5 mg/kg/dia i.p) em ratos. MÉTODOS: Ratos Wistar machos (n = 24) foram divididos em quatro grupos: Grupo controle; Grupo treinado; Grupo tratado com Dex e Grupo tratado com Dex e treinado. O treinamento físico (iniciado 72 horas após a primeira dose de Dex) foi realizado 3 vezes por semana, até o final do tratamento. Ao final desse período, realizaram-se as seguintes avaliações bioquímicas: glicemia em jejum, teste de tolerância à glicose e análise do perfil lipídico no sangue que incluiu colesterol total (CT), LDL-c, HDL-c, VLDL-c e triglicerídeos (TG). O peso do músculo gastrocnêmio, análise histopatológica do fígado e os índices cardiometabólicos (CT/HDL-c, LDL-c/HDL-c e TG/HDL-c) também foram avaliados. RESULTADOS: Observou-se hiperglicemia, menor tolerância à glicose, elevação do CT, LDL-c, VLDL-c e TG, diminuição do HDL-c, presença de esteatose hepática, hipotrofia muscular e elevação dos índices CT/HDL-c, LDL-c/HDL-c e TG/HDL-c nos animais tratados com Dex. O exercício físico reduziu a hiperglicemia, melhorou a tolerância à glicose, reduziu a dislipidemia e preveniu a esteatose hepática , a hipotrofia muscular e reduziu os índices CT/HDL-c, LDL-c/HDL-c e TG/HDL-c. Entretanto, não houve efeito significante do treinamento físico sobre o HDL-c. CONCLUSÃO: O exercício físico aeróbio tem efeito protetor contra as alterações cardiometabólicas induzidas pelo uso crônico de glicocorticóides.

BACKGROUND: Chronically, glucocorticoids induce adverse cardiometabolic alterations including insulin resistance, diabetes, dyslipidemia, liver steatosis and arterial hypertension. OBJECTIVES: To evaluate the effect of regular practice of aerobic exercise on cardiometabolic alterations induced by chronic administration of dexamethasone (Dex - 0.5 mg/kg/day ip) in rats. METHODS: Male Wistar rats (n = 24) were divided in four groups: Control group; Trained group; Treated with Dex group and Treated with Dex and trained group. The exercise training (initiated 72 hours after the first dose of Dex) was carried out three times a week until the end of the treatment. At the end of this period, the following biochemical assessments were performed: fasting glycemia, oral glucose tolerance test and analysis of the blood lipid profile that included total cholesterol (TC), LDL-c, HDL-c, VLDL-c and triglycerides (TG). The weight of the gastrocnemius muscle, the histopathological analysis of the liver and cardiometabolic indices (TC/HDL-c, LDL-c/HDL-c and TG/HDL-c) were also performed. RESULTS: Hyperglycemia, lower glucose tolerance, increased TC, LDL-c, VLDL-c, TG, CT/HDL-c, LDL-c/HDL-c and TG/HDL-c, decreased HDL-c, presence of liver steatosis and muscular hypotrophy were observed in the animals treated with Dex. The exercise training reduced hyperglycemia, improved glucose tolerance, decreased dyslipidemia and prevented liver steatosis, muscular hypotrophy and reduced CT/HDL-c, LDL-c/HDL-c and TG/HDL-c ratios. However, there was no significant effect on HDL-c. CONCLUSION: The aerobic exercise training have a protective effect against the cardiometabolic alterations induced by the chronic use of glucocorticoids.

Perfil lipídico, fatores de risco cardiovascular e síndrome metabólica em um grupo de pacientes com AIDS / Perfil lipídico, factores de riesgo cardiovascular y síndrome metabólico en un grupo de pacientes con SID / Lipid profile, cardiovascular risk factors and metabolic syndrome in a group of AIDS patients

FUNDAMENTO: Desde o advento da AIDS, a terapia antiretroviral desenvolveu-se significantemente, incluindo a terapia antiretroviral altamente ativa (HAART) e a doença adquiriu uma característica crônica. Entretanto, após a introdução da HAART, várias alterações metabólicas foram observadas, principalmente relacionadas ao perfil lipídico. OBJETIVO: Avaliar e comparar os perfis lipídicos, analisar o risco cardiovascular, e descrever a prevalência da síndrome metabólica em pacientes com AIDS tratados ou não com HAART. MÉTODOS: Durante um período de 18 meses, 319 pacientes tratados em ambulatórios na cidade de São Paulo, Brasil, foram selecionados. RESULTADOS: A amostra final incluiu 215 pacientes tratados com HAART e 69 pacientes virgens de tratamento com HAART. A idade média era 39,5 anos, e 60,9 por cento eram do sexo masculino. Os principais fatores de risco cardiovascular eram o fumo (27 por cento), hipertensão (18 por cento) e histórico familiar de aterosclerose (40 por cento). Os valores médios de colesterol total, HDL-colesterol, triglicérides e glicose foram mais altos no grupo HAART do que no grupo não-HAART (205 vs 180 mg/dl, 51 vs 43 mg/dl, 219 vs 164 mg/dl e 101 vs 93 mg/dl respectivamente; p < 0,001 para todos). De acordo com o escore de risco de Framingham, o risco cardiovascular era moderado a alto em 11 por cento dos pacientes tratados com HAART e 4 por cento dos pacientes não-HAART. De acordo com a definição do Adult Treatment Panel III, a síndrome metabólica foi observada em 13 por cento e 12 por cento dos pacientes, respectivamente, com e sem HAART. CONCLUSÃO: Embora os valores médios do colesterol total, HDL-c e triglicérides tenham sido mais altos no grupo HAART, um maior risco cardiovascular não foi identificado no primeiro grupo. A prevalência de síndrome metabólica foi comparável em ambos os grupos.

BACKGROUND: Since the advent of AIDS, the anti-HIV therapy has developed significantly, including the highly active antiretroviral therapy (HAART) and the disease acquired a chronic characteristic. However, after the introduction of HAART, several metabolic alterations were observed, mainly related to the lipid profile. OBJECTIVES: to evaluate and compare lipid profiles, analyze cardiovascular risk, describe the prevalence of metabolic syndrome in AIDS patients with or without HAART. METHODS: Over an 18-month period, 319 patients treated at outpatient clinics in the city of São Paulo, Brazil were selected. RESULTS: The final sample included 215 patients receiving HAART and 69 HAART-naive patients. The mean age was 39.5 years, and 60.9 percent were males. The main cardiovascular risk factors were smoking (27 percent), hypertension (18 percent) and family history of atherosclerosis (40 percent). Mean total cholesterol, HDL-cholesterol, triglycerides and glucose were higher in the HAART group than in the non-HAART group (205 vs 180 mg/dl, 51 vs 43 mg/dl, 219 vs 164 mg/dl and 101 vs 93 mg/dl respectively; p < 0.001 for all). According to the Framingham risk score, the cardiovascular risk was moderate to high in 11 percent of the patients receiving HAART and 4 percent of the HAART-naïve patients. According to the Adult Treatment Panel III definition, the metabolic syndrome was observed in 13 percent and 12 percent of the patients with or without HAART, respectively. CONCLUSIONS: Although the mean values for total cholesterol, HDL-c and triglycerides were higher in the HAART group, a higher cardiovascular risk was not identified in the former. The prevalence of metabolic syndrome was comparable in both groups.

FUNDAMENTO: Desde el surgimiento del SIDA, la terapia antiretroviral se desarrolló significantemente. Al incluir la terapia antiretroviral altamente activa (HAART), la enfermedad adquirió una característica crónica. Sin embargo, tras la introducción de HAART, diversas alteraciones metabólicas se observaron, principalmente relacionadas al perfil lipídico. OBJETIVO: Evaluar y comparar los perfiles lipídicos, analizar el riesgo cardiovascular, y describir la prevalencia del síndrome metabólico en pacientes con SIDA tratados o no con HAART. MÉTODOS: Durante un período de 18 meses, se seleccionaron a 319 pacientes tratados en ambulatorios en la ciudad de São Paulo, Brasil. RESULTADOS: La muestra final incluyó a 215 pacientes tratados con HAART y a 69 pacientes vírgenes de tratamiento con HAART. La edad promedio era de 39,5 años, y el 60,9 por ciento eran del sexo masculino. Los principales factores de riesgo cardiovascular eran el fumo (27 por ciento), hipertensión (18 por ciento) e histórico familiar de aterosclerosis (40 por ciento). Los valores promedios de colesterol total, HDL-colesterol, triglicéridos y glucosa fueron más altos en el Grupo HAART que en el Grupo no-HAART (205 vs. 180 mg/dL, 51 vs. 43 mg/dL, 219 vs. 164 mg/dL, 101 vs. 93 mg/dL respectivamente; p < 0,001 para todos). De conformidad con el score de riesgo de Framingham, el riesgo cardiovascular era moderado y alto en el 11 por ciento de los pacientes tratados con HAART y el 4 por ciento de los pacientes no-HAART. Según la definición del Adult Treatment Panel III, el síndrome metabólico se observó en el 13 por ciento y el 12 por ciento de los pacientes, respectivamente, con y sin HAART. CONCLUSIÓN: Aunque los valores promedios del colesterol total, HDL-c y triglicéridos fueron más altos en el Grupo HAART, un mayor riesgo cardiovascular no se identificó en el primer grupo. La prevalencia de síndrome metabólico fue comparable en ambos grupos.

Efeitos da administração de metformina sobre a pressão arterial e o metabolismo glicídico de ratos espontaneamente hipertensos tornados obesos pela injeção neonatal de glutamato monossódico / Metformin effects upon blood pressure and glucose metabolism of monossodium glutamate induced-obese spontaneously hypertensive rats

OBJETIVOS: Produzir um modelo experimental de síndrome metabólica (SM) e analisar efeitos da metformina sobre pressão arterial (PA), peso corporal (PC), metabolismo glicídico e conteúdo de gordura epididimal (GE). MÉTODO: Os machos SHR receberam 2 mg/kg/dia de glutamato monossódico (MSG) até o 11º dia de vida. Os controles receberam salina. Após 12 semanas, foram separados em dois grupos e tratados com 500 mg/kg/dia de metformina ou veículo. Foram acompanhados a PA e o PC dos dois grupos. Ao final do seguimento, realizou-se o teste de tolerância à glicose oral (TTGO) e mediu-se o índice de sensibilidade à insulina. Após sacrifício dos animais, a GE foi pesada. RESULTADOS: A administração de MSG intensificou a resistência insulínica e aumentou o conteúdo de GE, sem, no entanto, alterar a PA. O tratamento com metformina promoveu melhora da sensibilidade insulínica e redução da GE e PA. CONCLUSÕES: Observou-se importante papel da resistência hepática à insulina na SM e efeitos cardiovasculares benéficos da melhora na sensibilidade insulínica.

OBJECTIVES: To make available experimental model for the metabolic syndrome (MS) and verify effects of chronic oral treatment with metformin upon blood pressure (BP), body weight (BW), glucose metabolism, epididimal fat content (EF). METHOD: Males SHR received monossodium glutamate (MSG, 2 mg/kg/day/sc) during first 11 days of life. Control animals received saline. After 12 weeks, animals were separated in two groups, treated either with metformin 500 mg/ kg/day or vehicle during 12 weeks. PA and BW were determined. At the end of the follow-up, animals underwent an oral glucose tolerance test (OGTT) and insulin sensitivity index was determined. Upon sacrifice EF was measured. RESULTS: MSG worsened insulin resistance and induced visceral obesity in SHR, without change BP. Treatment with metformin improved glucose metabolism and reduces EF and BP. CONCLUSIONS: These observations emphasize the role of hepatic insulin resistance on MS and point out for beneficial cardiovascular effects with improvement in the insulin sensitivity.

Consenso Brasileiro sobre antipsicóticos de segunda geração e distúrbios metabólicos: [revisão] / Brazilian Consensus on second-generation antipsychotics and metabolic disorders: [review]

OBJETIVO: Discutir os aspectos atuais do tratamento com os antipsicóticos, levando-se em consideração o perfil de efeitos metabólicos, tais como ganho de peso, diabetes, dislipidemias e síndrome metabólica. Tais fatores aumentam o risco de doença cardiovascular, que é a principal causa de morte nos portadores de esquizofrenia. MÉTODO: Foi realizada uma reunião de consenso com psiquiatras especialistas em esquizofrenia e endocrinologistas, os quais, com base nas evidências provenientes de ampla revisão da literatura, elaboraram um documento com recomendações que auxiliam a prática clínica. RESULTADOS E CONCLUSÕES: A avaliação periódica dos efeitos adversos metabólicos em pacientes que fazem uso de antipsicóticos é fundamental para a prática clínica, especialmente nos caso de antipsicóticos de segunda geração. O equilíbrio entre eficácia e tolerabilidade deve ser cuidadosamente considerado em todas as etapas do tratamento.

OBJECTIVE: To discuss current aspects of use of antipsychotics considering their metabolic side effects profile, which includes weight gain, dyslipidemias, diabetes and metabolic syndrome. Such metabolic effects increase the risk of mortality by cardiovascular disease, which is the leading cause of death among schizophrenic patients. METHOD: A consensus meeting was held, with participation of endocrinologists and psychiatrists specialists in schizophrenia and, based on a literature review, an article was elaborated emphasizing practical and helpful recommendations to clinicians. RESULTS AND CONCLUSIONS: Monitoring metabolic side effects is essential to patients taking antipsychotics, particularly in the case of second generation antipsychotics. Efficacy and tolerability should be carefully balanced in all phases of treatment.

Weight gain, dyslipidemia and altered parameters for metabolic syndrome on first episode psychotic patients after six-month follow-up

OBJECTIVES: Obesity and metabolic abnormalities are frequent in psychotic patients, including first-episode psychosis. We evaluated weight and metabolic parameters in first-episode psychotic outpatients from the First Episode Psychosis Program, Universidade Federal de São Paulo. METHOD: Weight, height, waist and hip circumferences, glucose and lipid levels were measured at baseline and after a six-month period. RESULTS: Fifty-seven patients were included and 44 (77.2 percent) of them finished the study. Patients had a median age of 26.3 years, 60 percent were men and 43 percent had a diagnosis of schizophrenia at the endpoint. Weight and BMI values increased significantly during the follow-up (p < 0.01). The average weight gain at the follow-up was 10.1 percent of the baseline weight (SD = 11.9). Only women presented significant waist abnormalities: at the first assessment the waist mean was 79.12 cm (SD = 10.68) and 6 months later it had increased to 89.65 cm (SD = 11.19, z = -3.182, p = 0.001). After 6 months, the total cholesterol (p = 0.004), and triglyceride levels (p = 0.016) increased, while HDL-cholesterol levels decreased (p = 0.025). During the follow-up period one patient (2.3 percent) developed diabetes mellitus, one (2.3 percent) presented altered fasting glucose, 12 (27.2 percent) patients developed at least two altered parameters for metabolic syndrome and 3 (6.8 percent) patients developed metabolic syndrome (p = 0.001). DISCUSSION: The results of this study showed that in a short period of time individuals under antipsychotic treatment had their weight increased significantly and developed important metabolic abnormalities. CONCLUSIONS: Clinicians should be aware of these risks, choose an antipsychotic that causes less weight gain and should monitor these patients carefully, and recommend prophylactic measures as diet restriction and physical activities.

OBJETIVOS: Obesidade e alterações metabólicas são freqüentes em pacientes psicóticos, inclusive no primeiro episódio psicótico. Foram avaliados peso e parâmetros metabólicos em pacientes em tratamento no Programa de Episódio Psicótico da Universidade Federal de São Paulo. MÉTODO: Peso, altura, medida de cintura e quadril, glicemia e perfil lipídico foram avaliados no início do tratamento e após seis meses. RESULTADOS: Cinqüenta e sete pacientes foram incluídos no estudo e 44 (72 por cento) concluíram o estudo. Os pacientes apresentavam em média 26,3 anos, 60 por cento eram do sexo masculino e, ao final do estudo, 43 por cento apresentavam diagnóstico de esquizofrenia. Houve aumento significativo do peso e índice de massa corporal durante o estudo (p < 0,01). Em média, o peso aumentou 10,1 por cento do peso inicial (SD = 11,9). Apenas mulheres apresentaram alterações na medida da cintura: no início, a média da cintura era de 79,12 cm (SD = 10,68) e, após seis meses, houve um aumento para 89,65 cm (SD = 11,19, z = -3,182, p = 0,001). Após seis meses, houve aumento do colesterol total (p = 0,004) e triglicérides (p = 0,016), e diminuição dos níveis de colesterol HDL (p = 0,025). No período, um paciente (2,3 por cento) desenvolveu diabetes mellitus, um paciente (2,3 por cento) apresentou glicemia de jejum alterada, 12 (27,2 por cento) desenvolveram pelo menos dois parâmetros alterados para síndrome metabólica, e 3 (6,8 por cento) apresentaram síndrome metabólica (p = 0,001). DISCUSSÃO: Os resultados deste estudo mostram que em um curto período de tempo pacientes em tratamento com antipsicóticos aumentaram substancialmente o peso e desenvolveram importantes alterações metabólicas. CONCLUSÃO: Os clínicos devem estar atentos a esses riscos, escolher medicações que causem menor ganho de peso, devendo monitorar esses pacientes cuidadosamente e recomendar medidas profiláticas como restrição dietética e atividade física.

Distribuição da gordura corporal e perfis lipídico e glicêmico de pacientes infectados pelo HIV / Corporal fat distribution and lipidic and glicemic profiles of HIV-infected patients

Os objetivos foram avaliar dados antropométricos e perfis lipídico e glicêmico de pacientes infectados pelo HIV usuários e não usuários de anti-retrovirais (ARV), e verificar a associação entre ARV e alterações da gordura corporal, distúrbios lipídicos e da homeostase da glicose. Foram incluídos 176 pacientes (133 usuários e 43 não usuários de ARV). Os pacientes foram submetidos a avaliação clínica, exames laboratoriais, ultrassonografia, biompedanciometria e medida de pregas cutâneas. Pacientes usuários de ARV apresentaram maior relação cintura/quadril (p= 0,0002), maior espessura da gordura intra-abdominal medida pela ultrassonografia (p= 0,003) e menores pregas de gordura bicipital (p= 0,01) e tricipital (p= 0,0002). Estes pacientes tiveram níveis mais elevados de triglicérides (p= 0,0002), colesterol total (p= 0,00007) e colesterol HDL (p= 0,009). Eles também apresentaram maiores níveis de glicose aos 60 (p= 0,01) e 120 minutos (p= 0,001) após dextrosol, maiores níveis de insulina de jejum (p= 0,03) e maiores valores do índice HOMA (p= 0,02). As drogas anti-retrovirais estão associadas a acúmulo central e perda periférica de gordura. Além disso, estas drogas estão associadas a alterações lipídicas e a aumento da resistência insulínica, conhecidos fatores de risco cardiovascular.

The aims of this study were to describe anthropometric data and glycemic and lipidic profiles of HIV-infected patients treated or not with antiretrovirals (ARV) drugs, and to assess association between these drugs and body composition changes, lipid and glucose homeostasis disturbances. There were 176 patients included (133 ARV-treated patients and 43 ARV-naïve). The patients were submitted to clinical evaluation, laboratorial analysis, ultrasonographic measurements, bioelectrical impedance analysis and skin folds thickness measurements. The ARV-treated group showed higher waist-to-hip ratio (p= 0.0002), higher intra-abdominal fat thickness measured by ultrasonography (p= 0.003) and lower bicipital (p= 0.01) and tricipital (p= 0.0002) skin folds. This group also showed higher triglyceride (p= 0.0002), total cholesterol (p= 0.00007), HDL cholesterol (p= 0.009), glucose measurements one hour (p= 0.01) and two hours (p= 0.001) after dextrose load, higher levels of fasting insulin (p= 0.03) and higher HOMAR index (p= 0.02). The antiretroviral drugs are associated with increased visceral fat and decreased peripheral fat pads. Beside that, these drugs are associated with atherogenic lipid profile and insulin resistance, two independent risk predictors of cardiovascular disease.