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.

Características clínicas de los pacientes con hipertrigliceridemia remitidos a las Unidades de Lípidos: registro de hipertrigliceridemias de la Sociedad Española de Arteriosclerosis / Clinical features of patients with hypertriglyceridemia referred to lipid units: registry of hypertrigliceridemia of the Spanish Arteriosclerosis Society

Fundamento y objetivoDescribir las características clínicas de sujetos con hipertrigliceridemia remitidos a Unidades de Lípidos asociadas a la Sociedad Española de Arteriosclerosis (ULSEA).Pacientes y métodoSe trata de un estudio multicéntrico, prospectivo y observacional, de pacientes con valores de triglicéridos séricos > 200mg/dl, reclutados desde enero 2007 a diciembre de 2008. Se recogieron variables demográficas, antecedentes, consumo de medicamentos, antropometría, diagnóstico y variables analíticas de la visita de inclusión.Resultados: Se incluyeron 1.033 varones y 361 mujeres con edad media (DE) de 50 (12) años. La enfermedad vascular previa, el tabaquismo, el consumo de alcohol y la esteatosis hepática fueron mayores en los varones que en las mujeres; en ellas fueron más prevalentes la hipertensión, la diabetes y la obesidad abdominal. La actividad física habitual y la dieta cardiosaludable fue seguida escasamente en ambos sexos. La mayor parte de los pacientes tenían una hipertrigliceridemia primaria (54%), especialmente una hiperlipemia familiar combinada o una hipertrigliceridemia familiar. La obesidad, el alcohol y la diabetes fueron las causas más comunes de hipertrigliceridemia secundaria. Un 27% de los pacientes se trataban con dieta, un 44% con fármacos en monoterapia y el resto (24%) con diversas combinaciones. Conclusiones: Aunque predominan las causas primarias, se constata una elevada frecuencia de etiologías secundarias y de trastornos que agravan la hipertrigliceridemia, predominando el tabaquismo y el consumo de alcohol en los varones y la obesidad abdominal y la diabetes en las mujeres. Aunque muchos pacientes reciben terapia farmacológica, se evidencia un amplio margen para mejorar la dieta y reducir el sedentarismo (AU)

Background and objective: to show clinical features of subjects with hypertriglyceridemia (HTG) referred to the Lipid Units associated to Spanish Arteriosclerosis Society (ULSEA).Patients and method: it is a prospective, cross-sectional, multicentric study of patients with serum Tgs > 200mg/dL, recruited from January 2007 to December 2008. Demographic, drug therapies, anthropometrical, main diagnosis and biochemical parameters were registered. Results: We included 1,033 men and 361 women, 50±12 years-old. Vascular disease, smoking, alcohol intake and liver steatosis were more prevalent in men than in women; by contrast, hypertension, diabetes and abdominal obesity were they in women. Regular physical exercise and a healthy diet were kept sparsely. Most patients suffered from a primary HTG (54%), mainly familial combined hyperlipidemia or familial hypertriglyceridemia. Obesity, alcohol intake and diabetes were the most common secondary forms of HTG. Among patients, 27% were diet-only treated, 44% received drugs in monotherapy and 24% drugs in combinations. Conclusions: Although primary forms of HTG are common, we show here a high prevalence of secondary forms and conditions worsening the HTG, being smoking and alcohol intake in men and abdominal obesity and diabetes in women. Even though most patients are drug-treated, diet and regular exercise recommendations should be clearly improved (AU)

[Clinical features of patients with hypertriglyceridemia referred to lipid units: registry of hypertrigliceridemia of the Spanish Arteriosclerosis Society]. / Características clínicas de los pacientes con hipertrigliceridemia remitidos a las Unidades de Lípidos: registro de hipertrigliceridemias de la Sociedad Española de Arteriosclerosis.

BACKGROUND AND OBJECTIVE: to show clinical features of subjects with hypertriglyceridemia (HTG) referred to the Lipid Units associated to Spanish Arteriosclerosis Society (ULSEA). PATIENTS AND METHOD: it is a prospective, cross-sectional, multicentric study of patients with serum Tgs > 200mg/dL, recruited from January 2007 to December 2008. Demographic, drug therapies, anthropometrical, main diagnosis and biochemical parameters were registered. RESULTS: We included 1,033 men and 361 women, 50±12 years-old. Vascular disease, smoking, alcohol intake and liver steatosis were more prevalent in men than in women; by contrast, hypertension, diabetes and abdominal obesity were they in women. Regular physical exercise and a healthy diet were kept sparsely. Most patients suffered from a primary HTG (54%), mainly familial combined hyperlipidemia or familial hypertriglyceridemia. Obesity, alcohol intake and diabetes were the most common secondary forms of HTG. Among patients, 27% were diet-only treated, 44% received drugs in monotherapy and 24% drugs in combinations. CONCLUSIONS: Although primary forms of HTG are common, we show here a high prevalence of secondary forms and conditions worsening the HTG, being smoking and alcohol intake in men and abdominal obesity and diabetes in women. Even though most patients are drug-treated, diet and regular exercise recommendations should be clearly improved.

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis.

BACKGROUND: Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. METHODS: Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. RESULTS: Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). CONCLUSION: Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during childhood.

Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report.

BACKGROUND: Mixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day. METHODS: Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA. RESULTS: The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05). CONCLUSION: Our preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.