Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (II). Tratamiento de la enfermedad del hígado graso no alcohólico / Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease

La enfermedad del hígado graso no alcohólico (EHGNA) comprende una serie de lesiones hepáticas histológicamente similares a las inducidas por el alcohol en personas con un consumo del mismo muy escaso o nulo. La importancia de la EHGNA radica en su alta prevalencia en nuestras sociedades occidentales y, desde el punto de vista hepático, en su progresiva evolución desde esteatosis a esteatohepatitis, cirrosis y cáncer de hígado. Durante la última década se ha observado que la EHGNA da lugar a un incremento del riesgo cardiovascular con aceleración de la arteriosclerosis y de los episodios cardiovasculares, principal causa de su morbimortalidad. Esta revisión actualizada a enero de 2016 consta de 2 partes. En esta segunda parte se revisarán el tratamiento de la EHGNA y su influencia sobre la enfermedad cardiovascular, así como los fármacos empleados en el control de los factores de riesgo cardiovascular que muestran un efecto beneficioso sobre esta hepatopatía (AU)

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed (AU)

Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (I). Enfermedad del hígado graso no alcohólico y su asociación con la enfermedad cardiovascular / Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease

La enfermedad del hígado graso no alcohólico (EHGNA) comprende una serie de lesiones hepáticas histológicamente similares a las inducidas por el alcohol, en personas con un consumo del mismo muy escaso o nulo. La importancia de la EHGNA radica en su alta prevalencia en el mundo occidental y, desde el punto de vista hepático, en su progresiva evolución desde esteatosis a esteatohepatitis, cirrosis y cáncer de hígado. Durante la última década se ha observado que la EHGNA da lugar a un incremento del riesgo cardiovascular con aceleración de la arteriosclerosis y de los eventos a ella vinculados, principal causa de su morbimortalidad. Esta revisión actualizada a enero de 2016 consta de dos partes, analizando en esta primera parte la asociación de la EHGNA con la enfermedad cardiovascular (AU)

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease (AU)

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (II). Tratamiento de la enfermedad del hígado graso no alcohólico.

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (I). Enfermedad del hígado graso no alcohólico y su asociación con la enfermedad cardiovascular.

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease.

La auténtica dimensión del colesterol-no-HDL: colesterol aterogénico / The real measurement of non-HDL-cholesterol: Atherogenic cholesterol

Las lipoproteínas de baja densidad (LDL) son un agente causal de la enfermedad cardiovascular. En la práctica, se asume una identificación entre las LDL y el colesterol unido a las LDL (cLDL). De esta forma el cLDL se ha transformado en un objetivo prioritario para la prevención cardiovascular. Sin embargo, cada vez existen más evidencias de que las lipoproteínas ricas en triglicéridos, especialmente las de muy baja densidad (VLDL) son capaces de promover y desarrollar arteriosclerosis, transformando así el colesterol unido a VLDL (cVLDL) y sus remanentes en otro potencial objetivo terapéutico. Esto es particularmente importante, por su magnitud, en los individuos con hipertrigliceridemia. Podemos señalar, por tanto, que la suma del cLDL más cVLDL y sus remanentes y el colesterol de la lipoproteína(a) -o lo que resulta similar, el colesterol-no-HDL (c-no-HDL)-. Además, la concentración de c-no-HDL no muestra variaciones significativas en el estado de ayunas o posprandial. En consecuencia, el c-no-HDL se ha transformado en un excelente indicador de colesterol aterogénico, y un objetivo terapéutico primordial en individuos con dislipidemia aterogénica. De acuerdo con los distintos ensayos clínicos, y los estudios epidemiológicos de base poblacional y genética, en los pacientes de muy alto riesgo, el nivel óptimo de cLDL es inferior a 70 mg/dl, y de c-no-HDL inferior a 100 mg/dl, mientras que en los de alto riesgo será 100 y 130 mg/dl, respectivamente

Lowe density lipoproteins (LDL) are the causal agent of cardiovascular diseases. In practice, we identify LDL with cholesterol transported in LDL (cLDL). So, cLDL has become the major target for cardiovascular prevention. Howewer, we have progressive evidences about the role of triglycerides rich lipoproteins, particularly those very low density lipoprotein (VLDL) in promotion and progression of atherosclerosis, that leads cholesterol in VLDL and its remanents as a potential therapeutic target. This feature is particularly important and of a great magnitude, in patients with hypertiglyceridemia. We can to considere, that the non-HDL cholesterol -cLDL+cVLDL+c-remmants+Lp(a)- is the real measurement of atherogenic cholesterol. In addition, non-HDL-cholesterol do not show any variations between postprandial states. In fact, non-HDL-cholesterol should be an excellent marker of atherogenic cholesterol, and an major therapeutic target in patients with atherogenic dyslipidaemia. According with different clinical trials and with the epidemiological and mendelian studies, in patients with high cardiovascular risk, optimal level of cLDL will be under 70 mg/dl, and under 100 ng/dl for non-HDL-cholesterol; and in high risk patients, 100 mg/dl and 130 mg/dl, respectivel (AU)

Terapia con fibratos: uso racional del fenofibrato 2016. Resumen ejecutivo / Fibrates therapy: Rational use fenofibrate 2016. Executive summary

En el control de los factores de riesgo lipídicos, y con independencia de un correcto manejo del cLDL acorde con el nivel de riesgo individual, se debe considerar la detección y tratamiento de la dislipidemia aterogénica y de los niveles anormales de triglicéridos o de cHDL para abordar una protección cardiovascular global, tanto en prevención primaria como secundaria. En tal sentido, estas recomendaciones recogen los datos de eficacia y seguridad de la combinación de estatina con los fibratos, frecuentemente necesaria para el control global de la dislipidemia, especialmente en los enfermos con alteraciones metabólicas tales como diabetes mellitus, síndrome metabólico u obesidad visceral. También se hace referencia al proceso de control y seguimiento del tratamiento, así como al valor añadido que pueden aportar los beneficios derivados del tratamiento con fenofibrato, que no se ligan directamente a su efecto hipolipemiante

To control lipid factors risk, beyond proper management of LDL cholesterol according to individual risk, detection and treatment of atherogenic dyslipidemia and abnormal levels of triglycerides or HDL cholesterol it should be considered for address a global cardiovascular protection, both in primary and secondary prevention. In this sense, these recommendations collect data on efficacy and safety about the combination statin with fibrates, often necessary for total control of dyslipidemia, particularly in patients with metabolic disorders such as diabetes mellitus, metabolic syndrome or visceral obesity. Reference to control and monitoring of treatment is also done, as well as benefits of fenofibrate not linked directly to their lipid-lowering effect

[The real measurement of non-HDL-cholesterol: Atherogenic cholesterol]. / La auténtica dimensión del colesterol-no-HDL: colesterol aterogénico.

Lowe density lipoproteins (LDL) are the causal agent of cardiovascular diseases. In practice, we identify LDL with cholesterol transported in LDL (cLDL). So, cLDL has become the major target for cardiovascular prevention. Howewer, we have progressive evidences about the role of triglycerides rich lipoproteins, particularly those very low density lipoprotein (VLDL) in promotion and progression of atherosclerosis, that leads cholesterol in VLDL and its remanents as a potential therapeutic target. This feature is particularly important and of a great magnitude, in patients with hypertiglyceridemia. We can to considere, that the non-HDL cholesterol -cLDL+cVLDL+c-remmants+Lp(a)- is the real measurement of atherogenic cholesterol. In addition, non-HDL-cholesterol do not show any variations between postprandial states. In fact, non-HDL-cholesterol should be an excellent marker of atherogenic cholesterol, and an major therapeutic target in patients with atherogenic dyslipidaemia. According with different clinical trials and with the epidemiological and mendelian studies, in patients with high cardiovascular risk, optimal level of cLDL will be under 70mg/dl, and under 100 ng/dl for non-HDL-cholesterol; and in high risk patients, 100mg/dl and 130mg/dl, respectively.

[Fibrates therapy: Rational use fenofibrate 2016. Executive summary]. / Terapia con fibratos: uso racional del fenofibrato 2016. Resumen ejecutivo.

To control lipid factors risk, beyond proper management of LDL cholesterol according to individual risk, detection and treatment of atherogenic dyslipidemia and abnormal levels of triglycerides or HDL cholesterol it should be considered for address a global cardiovascular protection, both in primary and secondary prevention. In this sense, these recommendations collect data on efficacy and safety about the combination statin with fibrates, often necessary for total control of dyslipidemia, particularly in patients with metabolic disorders such as diabetes mellitus, metabolic syndrome or visceral obesity. Reference to control and monitoring of treatment is also done, as well as benefits of fenofibrate not linked directly to their lipid-lowering effect.

El papel de la dislipemia aterogénica en las guías de práctica clínica / The role of atherogenic dyslipidaemia in clinical practice guidelines

Antecedentes y objetivo: La dislipemia aterogénica está frecuentemente infradiagnosticada e infratratada. El objetivo del presente estudio ha sido revisar el posicionamiento de las guías de práctica clínica con respecto a la dislipemia aterogénica. Material y método: A partir de la base de datos MEDLINE se recogieron las principales guías de práctica clínica de las sociedades científicas u organismos oficiales emitidas entre el 1 de enero de 2012 y el 31 marzo de 2015. De las 10 guías seleccionadas se identificaron los siguientes parámetros: colesterol de las lipoproteínas de alta densidad (HDL), triglicéridos, colesterol no HDL, apolipoproteína (apo) B y dislipemia aterogénica. De cada uno de ellos se valoró si eran considerados un factor de riesgo cardiovascular, si establecían algún objetivo terapéutico y si proponían algún tratamiento farmacológico específico. Resultados: Las guías americanas, excepto la National Lipid Association (NLA), no consideran el colesterol HDL y los triglicéridos en la prevención cardiovascular. La NLA resalta la relevancia de la dislipemia aterogénica. Por su parte, la guía canadiense introduce el colesterol no HDL y la apo B como objetivos alternativos y propone tratamiento con fármacos hipolipemiantes distintos de las estatinas en presencia de colesterol HDL bajo e hipertrigliceridemia. Las recomendaciones de la International Atherosclerosis Society (IAS) y del National Institute for Health and Care Excellence (NICE) promueven la importancia del colesterol no HDL. Las guías europea, brasileña y japonesa ponen en valor el colesterol HDL y los triglicéridos, aunque con la limitación de que las principales evidencias proceden de subanálisis de estudios clínicos. Conclusiones: Las guías de práctica clínica analizadas o no consideran la importancia de la dislipemia aterogénica o la abordan de forma poco convincente

Background and objective: Atherogenic dyslipidaemia is underdiagnosed, undertreated, and under-controlled. The aim of the present study was to assess the positioning of clinical guidelines as regards atherogenic dyslipidaemia. Material and method: The major clinical guidelines of scientific societies or official agencies issued between January 1, 2012 and March 31, 2015 were collected from the MEDLINE database. High-density lipoprotein (HDL) cholesterol, triglycerides, atherogenic dyslipidaemia, non-HDL cholesterol, and apolipoprotein (apo) B were gathered from the 10 selected guidelines, and it was assessed whether these parameters were considered a cardiovascular risk factor, a therapeutic target, or proposed a pharmacological strategy. Results: American guidelines, except the National Lipid Association (NLA), do not consider HDL cholesterol and triglycerides in cardiovascular prevention. The NLA emphasises the relevance of atherogenic dyslipidaemia. The Canadian guidelines introduced non-HDL cholesterol and Apo B as alternative targets, and proposes non-statin treatment in the presence of low HDL cholesterol and hypertriglyceridaemia. The International Atherosclerosis Society (IAS) and National Institute for Health and Care Excellence (NICE) guidelines promote the importance of non-HDL cholesterol. European, Brazilian and Japanese guidelines highlight HDL cholesterol and triglycerides, but with the limitation that the main evidence comes from sub-analysis of clinical studies. Conclusions: The clinical guidelines analysed do not consider, or unconvincingly address, the importance of atherogenic dyslipidaemia

[The role of atherogenic dyslipidaemia in clinical practice guidelines]. / El papel de la dislipemia aterogénica en las guías de práctica clínica.

BACKGROUND AND OBJECTIVE: Atherogenic dyslipidaemia is underdiagnosed, undertreated, and under-controlled. The aim of the present study was to assess the positioning of clinical guidelines as regards atherogenic dyslipidaemia. MATERIAL AND METHOD: The major clinical guidelines of scientific societies or official agencies issued between January 1, 2012 and March 31, 2015 were collected from the MEDLINE database. High-density lipoprotein (HDL) cholesterol, triglycerides, atherogenic dyslipidaemia, non-HDL cholesterol, and apolipoprotein (apo) B were gathered from the 10 selected guidelines, and it was assessed whether these parameters were considered a cardiovascular risk factor, a therapeutic target, or proposed a pharmacological strategy. RESULTS: American guidelines, except the National Lipid Association (NLA), do not consider HDL cholesterol and triglycerides in cardiovascular prevention. The NLA emphasises the relevance of atherogenic dyslipidaemia. The Canadian guidelines introduced non-HDL cholesterol and ApoB as alternative targets, and proposes non-statin treatment in the presence of low HDL cholesterol and hypertriglyceridaemia. The International Atherosclerosis Society (IAS) and National Institute for Health and Care Excellence (NICE) guidelines promote the importance of non-HDL cholesterol. European, Brazilian and Japanese guidelines highlight HDL cholesterol and triglycerides, but with the limitation that the main evidence comes from sub-analysis of clinical studies. CONCLUSIONS: The clinical guidelines analysed do not consider, or unconvincingly address, the importance of atherogenic dyslipidaemia.

Alzheimer's like brain changes correlate with low adiponectin plasma levels in type 2 diabetic patients.

AIM: To study the association between adiponectin plasma levels, and gray matter brain volume and cerebral glucose metabolism in a group of type 2 diabetes patients. METHODS: We studied 25 type 2 diabetes patients and 25 age- and gender-matched healthy control participants. Biochemical analysis and structural cerebral magnetic resonance imaging, including voxel-based morphometry and (18)-fluorodeoxyglucose positron emission tomography, were performed. The gray matter volumes and metabolism changes were analyzed using statistical parametric mapping (SPM8). RESULTS: Lower levels of adiponectin correlated with a lower gray matter volume in temporal regions and with reduced cerebral glucose metabolism in temporal regions (p<0.001), adjusted for age, gender, education, and the presence of at least one epsilon 4 allele for the apolipoprotein E (APOEε4 genotype). CONCLUSIONS: Positive correlations between adiponectin plasma levels and both gray matter volume and cerebral glucose metabolism were found, predominantly in temporal regions, as in Alzheimer's disease. Adiponectin might be a biomarker for the cognitive decline associated with type 2 diabetic patients.

Análogos del glucagon-like peptide-1 (GLP-1): ¿una nueva estrategia de tratamiento para la enfermedad de Alzheimer? / Glucagon-like peptide-1 (GLP-1) mimetics: a new treatment for Alzheimer's disease?

Introducción. Los análogos del glucagon-like peptide-1 (GLP-1) son una opción terapéutica establecida en los pacientes con diabetes tipo 2. Sin embargo, las propiedades de los análogos del GLP-1 van más allá del control estrictamente metabólico del paciente diabético. Los efectos neuroprotectores de los análogos del GLP-1 se han puesto de manifiesto en estudios recientes y han abierto nuevos campos de investigación en trastornos neurodegenerativos como la enfermedad de Alzheimer (EA), entre otros. Objetivo. Revisión sistemática de los estudios experimentales y ensayos clínicos en humanos que demuestran las propiedades neuroprotectoras de los análogos del GLP-1 en la EA. Desarrollo. Los estudios experimentales que se han llevado a cabo en modelos de roedores con EA demuestran las propiedades neuroprotectoras de los análogos del GLP-1 sobre el sistema nervioso central que reducen las placas de β-amiloide, el estrés oxidativo y la respuesta inflamatoria cerebral. Recientemente se han puesto en marcha estudios con análogos del GLP-1 en humanos con deterioro cognitivo y EA. Conclusiones. Los análogos del GLP-1 presentan propiedades neuroprotectoras. Al considerarse la diabetes tipo 2 un factor de riesgo para el deterioro cognitivo y la demencia, deben considerarse los beneficios de los análogos del GLP-1 sobre la cognición. Del mismo modo, los análogos del GLP-1 suponen un tratamiento prometedor en la EA (AU)

Introduction. The glucagon-like peptide-1 (GLP-1) mimetics are an established therapeutic option for patients with type 2 diabetes. However, the properties of the GLP-1 mimetics go beyond the strict metabolic control of the patients with diabetes. The neuroprotective effects of GLP-1 have been shown in recent studies opening new areas of research in neurodegenerative diseases such as Alzheimer’s disease (AD), among others. Aim. Systematic review including experimental studies and human clinical trials demonstrating the neuroprotective properties of GLP-1 mimetics in AD. Development. The experimental studies that have been conducted in rodent models of AD have demonstrated the neuroprotective properties of GLP-1 in the central nervous system reducing β-amyloid plaques, the oxidative stress and the inflammatory brain response. Clinical trials in patients with cognitive impairment and AD testing the effects of GLP-1 analogs have recently started. Conclusion. The GLP-1 analogs have neuroprotective properties. Considering that type 2 diabetes is a risk factor for cognitive impairment and dementia, the benefits of GLP-1 mimetics on cognition must be considered. Likewise, the GLP-1 mimetics represent a promising treatment for neurodegenerative diseases such as AD (AU)

[Glucagon-like peptide-1 (GLP-1) mimetics: a new treatment for Alzheimer's disease?]. / Análogos del glucagon-like peptide-1 (GLP-1): ¿una nueva estrategia de tratamiento para la enfermedad de Alzheimer?

INTRODUCTION: The glucagon-like peptide-1 (GLP-1) mimetics are an established therapeutic option for patients with type 2 diabetes. However, the properties of the GLP-1 mimetics go beyond the strict metabolic control of the patients with diabetes. The neuroprotective effects of GLP-1 have been shown in recent studies opening new areas of research in neurodegenerative diseases such as Alzheimer's disease (AD), among others. AIM. Systematic review including experimental studies and human clinical trials demonstrating the neuroprotective properties of GLP-1 mimetics in AD. DEVELOPMENT: The experimental studies that have been conducted in rodent models of AD have demonstrated the neuroprotective properties of GLP-1 in the central nervous system reducing beta-amyloid plaques, the oxidative stress and the inflammatory brain response. Clinical trials in patients with cognitive impairment and AD testing the effects of GLP-1 analogs have recently started. CONCLUSION: The GLP-1 analogs have neuroprotective properties. Considering that type 2 diabetes is a risk factor for cognitive impairment and dementia, the benefits of GLP-1 mimetics on cognition must be considered. Likewise, the GLP-1 mimetics represent a promising treatment for neurodegenerative diseases such as AD.

TITLE: Analogos del glucagon-like peptide-1 (GLP-1): una nueva estrategia de tratamiento para la enfermedad de Alzheimer?Introduccion. Los analogos del glucagon-like peptide-1 (GLP-1) son una opcion terapeutica establecida en los pacientes con diabetes tipo 2. Sin embargo, las propiedades de los analogos del GLP-1 van mas alla del control estrictamente metabolico del paciente diabetico. Los efectos neuroprotectores de los analogos del GLP-1 se han puesto de manifiesto en estudios recientes y han abierto nuevos campos de investigacion en trastornos neurodegenerativos como la enfermedad de Alzheimer (EA), entre otros. Objetivo. Revision sistematica de los estudios experimentales y ensayos clinicos en humanos que demuestran las propiedades neuroprotectoras de los analogos del GLP-1 en la EA. Desarrollo. Los estudios experimentales que se han llevado a cabo en modelos de roedores con EA demuestran las propiedades neuroprotectoras de los analogos del GLP-1 sobre el sistema nervioso central que reducen las placas de beta-amiloide, el estres oxidativo y la respuesta inflamatoria cerebral. Recientemente se han puesto en marcha estudios con analogos del GLP-1 en humanos con deterioro cognitivo y EA. Conclusiones. Los analogos del GLP-1 presentan propiedades neuroprotectoras. Al considerarse la diabetes tipo 2 un factor de riesgo para el deterioro cognitivo y la demencia, deben considerarse los beneficios de los analogos del GLP-1 sobre la cognicion. Del mismo modo, los analogos del GLP-1 suponen un tratamiento prometedor en la EA.

[The combinations of statins and fibrates: pharmacokinetic and clinical implications]. / Combinaciones de estatinas y fibratos: implicaciones farmacocinéticas y clínicas.

With mixed dyslipidemia of the atherogenic dyslipidemia type, once the LDL-c objectives have been achieved through statin treatment, there is often a residual risk, for which the addition of a fibrate is recommended. The combination of statins and fibrates has been limited by the possibility of drug interactions, which mostly result in myopathy. Interactions between statins and other drugs are caused by pharmacokinetic mechanisms, mainly by changing the metabolism of statins in the CYP450 enzyme system, in the hepatic glucuronidation pathway or in the transporters responsible for statin distribution in tissues. The most significant adverse eff ect of statins is myopathy, which can also be induced by fibrates and is more frequent when the 2 drugs (statins and fibrates) are combined. This adverse eff ect manifests clinically as myalgia, muscle weakness, increased CK levels and, in its most severe form, rhabdomyolysis. This interaction mainly aff ects gemfibrozil due to its specific action on the CYP450 enzyme system and that interferes with the hepatic glucuronidation of statins by using the same isoenzymes and with organic anion transporters in the liver. When combining statins, we should use other fibric acid derivatives, preferably fenofibrate.

Cognitive dysfunctions in middle-aged type 2 diabetic patients and neuroimaging correlations: a cross-sectional study.

BACKGROUND/OBJECTIVE: The aim was to assess the neuropsychological performance of a group of middle-aged patients with well-controlled type 2 diabetes mellitus (T2DM) and to examine whether the neuropsychological deficits correlate with structural and functional brain alterations. METHODS: We compared 25 subjects with T2DM aged 45-65 years with 25 control participants matched for age, gender, and educational level. The neuropsychological battery was designed to examine executive functions, attention, information processing speed, and verbal memory. Severity of depression was assessed using the Hamilton Depression Rating Scale and cardiovascular risk factors were assessed using the Framingham Cardiovascular Risk Profile Score. The presence of at least one APOEε4 allele was determined. Reduced gray matter density was analyzed using voxel-based morphometry and brain glucose metabolic changes were assessed by 18FDG-PET. RESULTS: T2DM subjects had significantly lower scores than subjects without T2DM in the Trail-making Test B (p < 0.004), Color-Word Stroop test (p < 0.005), Semantic Fluency (p < 0.006), Digit-Symbol modalities test (p < 0.02), Text Recall from the Wechsler Memory Scale (p < 0.0001), Rey-Osterrieth Complex Figure-copy (p < 0.004), and delayed reproduction (p < 0.03). Worse executive functions and memory functioning correlated predominantly with less gray matter density and reduced glucose metabolism in the orbital and prefrontal cortex, temporal (middle gyrus, parahippocampus and uncus), and cerebellum regions (p < 0.001). CONCLUSIONS: T2DM subjects presented cognitive dysfunctions compared with controls. Clinical-neuroimaging correlations corresponded to brain changes (reduced gray matter density and glucose metabolism) mainly in fronto-temporal areas.

Combinaciones de estatinas y fibratos: implicaciones farmacocinéticas y clínicas / The combinations of statins and fibrates: pharmacokinetic and clinical implications

En la dislipemia mixta del tipo de la dislipemia aterogénica, tras alcanzar los objetivos de colesterol unido a lipoproteínas de baja densidad (cLDL) mediante tratamiento con estatinas, persiste muchas veces un riesgo residual que aconseja la adición de un fibrato. La asociación de estatinas y fibratos ha sido limitada por la posibilidad de interacciones farmacológicas que determinan sobre todo miopatías. Las interacciones de las estatinas con otros fármacos se producen por mecanismos farmacocinéticos, fundamentalmente por alteración de su metabolismo a nivel del sistema enzimático CYP450, de la vía de la glucuronidación hepática o de los transportadores responsables de su distribución tisular. El efecto adverso más importante de las estatinas es la miopatía, que también puede ser inducida por los fibratos, y que resulta más frecuente cuando se asocian ambas medicaciones (estatinas y fibratos). Se manifiesta clínicamente por mialgias, debilidad muscular y/o elevaciones de creatinfosfocinasa, y en su forma más grave por rabdomiólisis. Esta interacción afecta fundamentalmente al gemfibrozilo, en base a su acción específica sobre el sistema enzimático citocromo P450 (CYP450), y a la interferencia con la glucuronidación hepática de las estatinas al utilizar las mismas isoenzimas, o con los transportadores de aniones orgánicos a nivel del hígado. Para asociar a estatinas, debemos utilizar otros derivados del ácido fíbrico, preferentemente fenofibrato

With mixed dyslipidemia of the atherogenic dyslipidemia type, once the LDL-c objectives have been achieved through statin treatment, there is often a residual risk, for which the addition of a fibrate is recommended. The combination of statins and fibrates has been limited by the possibility of drug interactions, which mostly result in myopathy. Interactions between statins and other drugs are caused by pharmacokinetic mechanisms, mainly by changing the metabolism of statins in the CYP450 enzyme system, in the hepatic glucuronidation pathway or in the transporters responsible for statin distribution in tissues. The most significant adverse eff ect of statins is myopathy, which can also be induced by fibrates and is more frequent when the 2 drugs (statins and fibrates) are combined. This adverse eff ect manifests clinically as myalgia, muscle weakness, increased CK levels and, in its most severe form, rhabdomyolysis. This interaction mainly aff ects gemfibrozil due to its specific action on the CYP450 enzyme system and that interferes with the hepatic glucuronidation of statins by using the same isoenzymes and with organic anion transporters in the liver. When combining statins, we should use other fibric acid derivatives, preferably fenofibrate

Use of expert consensus to improve atherogenic dyslipidemia management.

INTRODUCTION AND OBJECTIVES: Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up. METHODS: After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues. RESULTS: After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients. CONCLUSIONS: The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus.

Decálogo de recomendaciones clínicas en dislipidemia aterogénica / Decalogue of clinical recommendations on atherogenic dyslipidemia

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Structural and functional brain changes in middle-aged type 2 diabetic patients: a cross-sectional study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an emerging risk factor for cognitive impairment. Whether this impairment is a direct effect of this metabolic disorder on brain function, a consequence of vascular disease, or both, remains unknown. Structural and functional neuroimaging studies in patients with T2DM could help to elucidate this question. OBJECTIVE: We designed a cross-sectional study comparing 25 T2DM patients with 25 age- and gender-matched healthy control participants. Clinical information, APOE genotype, lipid and glucose analysis, structural cerebral magnetic resonance imaging including voxel-based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were obtained in all subjects. METHODS: Gray matter densities and metabolic differences between groups were analyzed using statistical parametric mapping. In addition to comparing the neuroimaging profiles of both groups, we correlated neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance measurement (HOMA-IR) in the diabetic patients group. RESULTS: Patients with T2DM presented reduced gray matter densities and reduced cerebral glucose metabolism in several fronto-temporal brain regions after controlling for various vascular risk factors. Furthermore, within the T2DM group, longer disease duration, and higher HbA1c levels and HOMA-IR were associated with lower gray matter density and reduced cerebral glucose metabolism in fronto-temporal regions. CONCLUSION: In agreement with previous reports, our findings indicate that T2DM leads to structural and metabolic abnormalities in fronto-temporal areas. Furthermore, they suggest that these abnormalities are not entirely explained by the role of T2DM as a cardiovascular risk factor.

Consenso de expertos sobre propuestas para la mejora del manejo de la dislipemia aterogénica / Use of expert consensus to improve atherogenic dyslipidemia management

Introducción y objetivos. La dislipemia aterogénica es un reconocido factor de riesgo cardiovascular; sin embargo, en la práctica clínica frecuentemente se subestima y, en consecuencia, está infratratada e infracontrolada. El objetivo es desarrollar un consenso multidisciplinario para establecer recomendaciones clínicas en torno a la dislipemia aterogénica para optimizar la prevención, la detección precoz, la valoración diagnóstica, el abordaje terapéutico y el seguimiento. Métodos. Tras la revisión de las evidencias científicas, el comité científico formuló 87 recomendaciones relacionadas con la dislipemia aterogénica, agrupadas en cinco áreas: conceptos generales (10 ítems), impacto y epidemiología (4 ítems), riesgo cardiovascular (32 ítems), detección y diagnóstico (19 ítems) y tratamiento (22 ítems). Se usó el método Delphi modificado en dos rondas para contrastar las opiniones de 65 expertos cardiólogos (el 23% de los encuestados), endocrinólogos (24,6%), médicos de atención primaria (27,7%) e internistas (24,6%). Resultados. Después de la primera ronda de acuerdo, se apreció consenso en 65 de las 87 cuestiones analizadas, que al final de la segunda ronda ascendió a 76 ítems. No se alcanzó un consenso suficiente en tres puntos sobre detección y diagnóstico de la dislipemia aterogénica y en tres aspectos de los objetivos terapéuticos que alcanzar en estos pacientes. Conclusiones. La valoración externa por expertos en dislipemia aterogénica constata un elevado nivel de acuerdo profesional con las recomendaciones clínicas propuestas. Estas recomendaciones constituyen un instrumento útil para la mejora del manejo clínico de los pacientes con dislipemia aterogénica. Las cuestiones en que no se alcanzó acuerdo precisan un análisis minucioso que permita señalar la evidencia científica actual (AU)

Introduction and objectives. Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up. Methods. After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues. Results. After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients. Conclusions. The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus (AU)