Diabetes como paradigma del impacto de las enfermedades no transmisibles

A proposal to redefine familial combined hyperlipidaemia -- third workshop on FCHL held in Barcelona from 3 to 5 May 2001, during the scientific sessions of the European Society for Clinical Investigation.

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Frailty Is Associated with Oxidative Stress in Older Patients with Type 2 Diabetes

Aging has increased the prevalence of frailty, and type 2 diabetes (T2D) has also increased in prevalence. Diabetes and oxidative stress (OS) have been shown to be related to frailty. However, the exact mechanism by which it occurs is not fully known. Our aim was to analyze body composition in community-dwelling older diabetic people treated in our center and to evaluate the possible relation between OS, frailty, and body composition. We included 100 adults older than 65 years with T2D. We found that 15% were frail and 57% were prefrail. The patients included in the nonrobust group showed increased levels of OS. Our study shows that the presence of T2D in the geriatric population is associa…

Homozygous Familial Hypercholesterolemia in Spain Prevalence and Phenotype-Genotype Relationship

Background— Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and LDL protein receptor adaptor 1 ( LDLRAP1 ). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results— Data were collected from the Spanish Dyslipidemia Regist…

Classical cardiovascular risk factors according to fasting plasma glucose levels

To compare the prevalence of classical cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) in our population according to fasting plasma glucose levels (FPG).We have studied 344 subjects between 20-70 years of age, recruited in a Primary Care Clinic. Subjects were divided into four groups according to their fasting plasma glucose (FPG) values: normal plasma glucose (NG) when FPG5.6 mmol/L; FPG between 5.6 and 6.0 mmol/L (FPG1); FPG between 6.1-6.9 mmol/L (FPG2); and diabetes (DM) FPGor = 7 mmol/L or previous diagnosis of diabetes. Cardiovascular risk factors (hypertension, TC/HDL-C index and Apo B values), presence of the MetS and indirect measure of insulin resistance (HOMA) w…

Gender differences on oxidative stress markers and complement component C3 plasma values after an oral unsaturated fat load test

Abstract Objective Post-prandial lipaemia (PL), oxidative stress (OS), and complement component C3 (C3) values are related to the atherosclerosis process. The post-prandial response of C3 after an oral fat load test (OFLT) using unsaturated fat is poorly addressed. The aim of this study was to analyze and compare the post-prandial response of OS markers and C3 values in men and women after an OFLT using unsaturated fat. Methods The study included a total of 22 healthy subjects with normal lipids and normal blood glucose (11 men and 11 pre-menopausal women). An oral unsaturated fat load test (OFLT: 50 g fat per m2 body surface) was performed using a commercial liquid preparation of long chai…

Insulin resistance aggravates atherosclerosis by reducing vascular smooth muscle cell survival and increasing CX3CL1/CX3CR1 axis.

Aims Insulin resistance (IR) is a major risk factor for cardiovascular disease and atherosclerosis. Life-threatening acute events are mainly due to rupture of unstable plaques, and the role of vascular smooth muscle cells (VSMCs) in this process in IR, Type 2 diabetes mellitus, and metabolic syndrome (T2DM/MetS) has not been fully addressed. Therefore, the role of VSMC survival in the generation of unstable plaques in T2DM/MetS and the involvement of inflammatory mediators was investigated. Methods and results Defective insulin receptor substrate 2 (IRS2)-mediated signalling produced insulin-resistant VSMCs with reduced survival, migration, and higher apoptosis than control cells. Silencing…

Insulin resistance and familial dyslipidaemias

Síndrome de McCune-Albright: otra forma de neoplasias endocrinas múltiples

Presentamos el caso de una mujer con sindrome de McCune-Albright como paradigma de afeccion tumoral en multiples glandulas endocrinas. El diagnostico de la enfermedad se baso en la presencia de la triada clasica (lesiones hiperpigmentadas cutaneas de color cafe con leche, pubertad precoz y displasia fibrosa). Durante su seguimiento presento hipertiroidismo secundario a bocio multinodular toxico, hiperparatiroidismo, probablemente secundario a hiperplasia paratiroidea, y acromegalia secundaria a adenoma hipofisario productor de hormona de crecimiento. Se comenta la base molecular de la enfermedad y su amplia expresion fenotipica.

Apo E phenotypes and plasma triglycerides in postmenopausal women with hormone replacement therapy

Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations?

Abstract Background: Familial hypercholesterolemia (FH) is a frequent form of autosomal-dominant hypercholesterolemia that predisposes to premature coronary atherosclerosis. FH is caused by sequence variations in the gene coding for the LDL receptor (LDLR). This gene has a wide spectrum of sequence variations, and genetic diagnosis can be performed by 2 strategies. Methods: Point variations and large rearrangements were screened along all the LDLR gene (promoter, exons, and flanking intron sequences). Results: We screened a sample of 129 FH probands from the Valencian Community, Spain, and identified 54 different LDLR sequence variations. The most frequent (10% of cases) was 111insA, and 60…

Respiratory chain polymorphisms and obesity in the Spanish population, a cross-sectional study

ObjectiveTo study the association of genes involved in the mitochondrial respiratory chain (MRC) pathway with body mass index (BMI) and obesity risk.DesignThis work studies three cross-sectional populations from Spain, representing three provinces: HORTEGA (Valladolid, Northwest/Centre), SEGOVIA (Segovia, Northwest/centre) and PIZARRA (Malaga,South).SettingForty-eight single nucleotide polymorphisms (SNPs) from MRC genes were selected and genotyped by SNPlex method. Association studies with BMI and obesity risk were performed for each population. These associations were then verified by analysis of the studied population as a whole (3731 samples).ParticipantsA total of 3731 Caucasian indivi…

Influence of Apo A4 genotypes (Apo4-347 mutation) on the lipid response to diet in familial hypercholesterolemia

Effects of a controlled program of moderate physical exercise on insulin sensitivity in nonobese, nondiabetic subjects.

OBJECTIVE: To study the effect of a moderate, aerobic physical exercise program on insulin resistance and its accompanying metabolic changes in a group of healthy, middle-age, nonobese subjects, without modifying oxygen consumption and body weight. DESIGN: The inclusion of subjects was carried out among volunteers from the health personnel of our center, who complied with the inclusion criteria. PARTICIPANTS: Twelve subjects (age 30-60 years, 5 females), nonsmokers, body mass index (BMI) <27 kg/m2 and fasting plasma glucose <6.1 mmol/L. INTERVENTIONS: Insulin resistance was assessed using the Bergmann minimal model modified with insulin, and basal and maximum metabolic rate were measured wi…

Estudio del defecto familiar de unión de la apolipoproteína B100 en una población mediterránea

Fundamento y objetivo Comparar las caracteristicas clinicobioquimicas del defecto familiar de union de la apolipoproteina B100 (DFB) con la hipercolesterolemia familiar (HF) heterocigota en una poblacion mediterranea del sur de Europa donde existen pocos datos al respecto, estudiar la prevalencia y el posible efecto fundador del DFB en una zona de la Comunidad Valenciana y conocer las caracteristicas clinicobioquimicas del DFB. Sujetos y metodo Hemos estudiado a 19 heterocigotos con DFB (8 varones) pertenecientes a 12 familias, portadores de la mutacion R3500Q del gen de la apolipoproteina B, y a 57 heterocigotos con HF (24 varones) geneticamente caracterizados, seleccionados de forma aleat…

Metabolismo lipídico y clasificación de las hiperlipemias

This chapter summarises, and updates, lipid metabolism. Both pathways, exogenous metabolisms route via the chylomicrons, and the endogenous pathway of very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The reverse cholesterol metabolism will also be mentioned. It also includes the current classification of hyperlipidaemias or hyperlipoproteinaemias, with a reminder of the phenotype classification, and further developments of the aetiological classification. Both parts have updated references, with which knowledge of this vast subject can be expanded.

Oxidative stress and antioxidant enzyme values in lymphomonocytes after an oral unsaturated fat load test in familial hypercholesterolemic subjects

Oxidative stress (OS) has been observed in conditions affecting the cardiovascular system. Familial hypercholesterolemia (FH) is associated with an increased risk of premature coronary heart disease. In the postprandial state, circulating lipids and lipoproteins can modulate OS status. Our aim was to study the response of lymphomonocyte OS status and reactive oxygen species by-products after an oral unsaturated fat load test (OFLT) in those with FH and to compare this response with that obtained in normolipidemic, normoglycemic subjects. We studied 12 patients with FH and 20 healthy controls. In both groups, lymphomonocyte, oxidized/reduced glutathione ratio, and malondialdehyde were determ…

Influencia del depósito de grasa abdominal en la respuesta terapéutica a atorvastatina en mujeres con hipercolesterolemia familiar heterocigota

Objetivo Analizar la influencia de parametros antropometricos (tipo y grado de obesidad) sobre el fenotipo lipoproteico y la respuesta terapeutica a atorvastatina en mujeres con Metodos Estudio de intervencion no controlado con 20 mg de atorvastatina al dia (dosis nocturna) en 34 mujeres con hipercolesterolemia familiar heterocigota seleccionadas de forma aleatoria. Resultados El deposito de grasa abdominal influye de forma estadisticamente significativa en los valores de presion arterial y concentraciones plasmaticas basales y postratamiento de los trigliceridos. Existe una interaccion negativa entre el deposito de grasa abdominal y la respuesta terapeutica de cLDL, siendo menores los desc…

The relation between obesity, abdominal fat deposit and the angiotensin-converting enzyme gene I/D polymorphism and its association with coronary heart disease.

To analyse the relation between overweight, obesity and fat distribution with I/D polymorphism of the angiotensin-converting enzyme (ACE) gene and its association with coronary heart disease (CHD). Cross-sectional, case–control study. A total of 185 cases (141 males) who had suffered at least one episode of CHD and 182 controls (127 males). Body mass index, waist circumference, blood pressure, plasma total cholesterol, triglycerides, HDL cholestrol and fasting glucose were measured with standard methods, genotyping the I/D polymorphism of ACE gene. Obesity and abdominal fat deposit are associated with CHD in women, but not independently. We have found an association between obesity and abdo…

NT3/TrkC pathway modulates the expression of UCP-1 and adipocyte size in human and murine adipose tissue

ABSTRACTNT3, through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (specially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 was present in human retroperitoneal AT and decreas…

Peripheral blood levels of CXCL10 are a useful marker for diabetic polyneuropathy in subjects with type 2 diabetes.

BACKGROUND Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus associated with high morbidity and mortality. Major risk factors for DPN include metabolic changes, duration of diabetes, nerve ischaemia and derangements in regeneration and nerve repair programmes. Chemokines have been previously implicated in the pathogenesis of various neuropathies and neuropathic pain processes. The aim of this pilot study was to evaluate the association between the plasma levels of chemokines (CXCL9, CXCL10 and CXCL11) in the presence of DPN in a cohort of type 2 diabetes (T2D) patients. MATERIALS AND METHODS We studied 73 patients with T2D: 36 with DPN and 37 without DPN. D…

Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia

BACKGROUND Thioredoxins (TRX) are major cellular protein disulphide reductases that are critical for redox regulation. Oxidative stress and inflammation play promoting roles in the genesis and progression of atherosclerosis, but until now scarce data are available considering the influence of TRX activity in familial combined hyperlipidaemia (FCH). Since FCH is associated with high risk of cardiovascular disease, the objective of the present study was to assess oxidative stress status in FCH patients, and evaluate the influence of insulin resistance (IR). MATERIALS AND METHODS A cohort of 35 control subjects and 35 non-related FCH patients were included, all of them nondiabetic, normotensiv…

Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy.

The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficien…

Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population: influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterol.

The aims of this study were to examine the presence of mutations in the low-density lipoprotein receptor gene among subjects clinically diagnosed with familial hypercholesterolemia and to analyze whether the molecular diagnosis helps to predict the response to simvastatin treatment in our familial hypercholesterolemia population. Fifty-five probands and 128 related subjects with familial hypercholesterolemia were studied. Genetic diagnosis was carried out following a three-step protocol based on Southern blot and PCR-single strand conformational polymorphism analysis. A randomized clinical trial with simvastatin was conducted in 42 genetically diagnosed subjects with familial hypercholester…

Altered glutathione system is associated with the presence of distal symmetric peripheral polyneuropathy in type 2 diabetic subjects.

Abstract Distal symmetric peripheral polyneuropathy (DSPN) is a highly prevalent complication of diabetes. However, underlying pathophysiological mechanisms are multiple and not well understood. The aim of our study was to analyze the oxidative stress levels in circulating mononuclear cells by measuring the glutathione system, malondialdehyde and oxidized-LDL, in 60 type 2 diabetic patients from a well-characterized cohort of 196 type 2 diabetic patients. Using a nested case–control design, we studied 30 type 2 diabetic patients with distal symmetric polyneuropathy and 30 diabetic controls without this complication, according to the Neuropathy Disability Score. We have found that diabetic p…

Homocisteína plasmática, Lp(a) y marcadores de estrés oxidativo en la vasculopatía periférica del paciente con diabetes tipo 2

Resumen Objetivo Buscar nuevos factores biologicos como el estres oxidativo (EO) y su interaccion con los clasicos, edad, HbA1c, Lp(a) y homocisteina plasmatica asociados con la vasculopatia periferica (VP) del paciente con diabetes tipo 2 (DMT2). Sujetos y metodos Estudiamos 204 diabeticos tipo 2 seleccionados de forma consecutiva de un hospital de referencia y un hospital comarcal de nuestra comunidad autonoma en el periodo comprendido entre enero de 2009 a mayo de 2010. Se trato de un estudio transversal de caso (ITB   1,2. Los parametros clinicobiologicos fueron medidos por procedimientos estandarizados. Resultados Los sujetos fueron divididos en 2 grupos: con VP (ITB > 0,89) o sin VP (…

AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia

Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG) metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on postprandial lipemia.Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined.Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39±8.36 mM*h/L) compared to homozygous carriers of the 1166-A allele (2.02±6.20 mM*h/L) (P&lt;0.05). Postprandial lipemia was similar…

Supresión del eje hipotálamohipofisario-suprarrenal por la exposición crónica a glucocorticoides de uso tópico. Presentación de dos casos clínicos

Presentamos 2 casos clinicos con psoriasis extensa en los que el mal uso prolongado de corticoides topicos indujo la supresion del eje hipotalamohipofisario- suprarrenal y, como consecuencia, una insuficiencia suprarrenal secundaria. Se comentan los mecanismos y los factores que pueden dar lugar a dicha supresion.

Anthropometric Indicators as a Tool for Diagnosis of Obesity and Other Health Risk Factors: A Literature Review

[EN] Obesity is characterized by the accumulation of an excessive amount of fat mass (FM) in the adipose tissue, subcutaneous, or inside certain organs. The risk does not lie so much in the amount of fat accumulated as in its distribution. Abdominal obesity (central or visceral) is an important risk factor for cardiovascular diseases, diabetes, and cancer, having an important role in the so-called metabolic syndrome. Therefore, it is necessary to prevent, detect, and appropriately treat obesity. The diagnosis is based on anthropometric indices that have been associated with adiposity and its distribution. Indices themselves, or a combination of some of them, conform to a big picture with di…

Pancitopenia en un varón de 59 años con feocromocitoma maligno tratado con I-131 metaiodobencilguanidina

Presentamos un paciente diagnosticado de feocromocitoma maligno silente que en su evolucion presento metastasis en cuerpos vertebrales, huesos iliacos, ambos pulmones e higado. El paciente solo referia lumbalgia intermitente y las determinaciones urinarias de catecolaminas y sus metabolitos fueron normales. Se realizo inicialmente suprarrenalectomia derecha y se aplico telecobaltoterapia externa en la region L4-S2 (dosis total de 20 Gy), para control del dolor y por inicio de compresion radicular. Posteriormente, de forma paliativa se administro una dosis unica de 200 mCi de 131-I metaiodobencilguanidina (MIBG), desarrollando al mes una pancitopenia con neutropenia grave, que preciso antibi…

Semiquantitative multiplex PCR: a useful tool for large rearrangement screening and characterization

Methods presently employed for detection of large rearrangements have several drawbacks, such as the amount of sample and time required, technical difficulty, or the probability of false-negative carriers. Using the low-density-lipoprotein receptor (LDLR) gene, whose mutations are responsible for familial hypercholesterolemia (FH), we have developed a procedure to detect large rearrangements in this gene based on semiquantitative PCR, with important improvements as compared to previous methods. Our method covers the complete LDLR gene and introduces an internal control in the reaction. The procedure discriminates the four different large rearrangements (two deletions and two insertions) tha…

Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients from a South European population

Few data are available on genotype-phenotype interactions among familial hypercholesterolemia (FH) patients in South European populations and there are no data about the influence of R3500Q mutation on lipoprotein phenotype compared to low-density lipoprotein receptor (LDLR) mutations. The objective of the study is to analyze the influence of mutations in the LDLR and apolipoprotein B (apoB) genes on lipoprotein phenotype among subjects clinically diagnosed of FH living in East Spain. In all, 113 FH index patients and 100 affected relatives were studied. Genetic diagnosis was carried out following a protocol based on Southern blot and PCR-SSCP analysis. A total of 118 FH subjects could be c…

Cuantificación de insulinorresistencia con los valores de insulina basal e índice HOMA en una población no diabética

Fundamento Calcular la prevalencia y definir el sindrome de insulinorresistencia mediante la determinacion de insulinemia basal y el indice HOMA, y estudiar su relacion con otros componentes del sindrome metabolico. Sujetos y metodo Estudiamos una poblacion de 292 sujetos no diabeticos, de ambos sexos y edades entre 20 y 65 anos, seleccionados por un metodo de muestreo simple aleatorio entre los que consultaron durante un ano en un centro de salud (en el area metropolitana de Valencia), mediante un metodo de busqueda oportunista. De ellos se selecciono a un subgrupo formado por 96 sujetos que no tenian caracteristicas clinicas ni analiticas del sindrome de insulinorresistencia, y se estudia…

Prevalence of plasma lipid abnormalities and its association with glucose metabolism in Spain: The di@bet.es study

Abstract Introduction Dyslipidemia is a significant contributor to the elevated CVD risk observed in type 2 diabetes mellitus. We assessed the prevalence of dyslipidemia and its association with glucose metabolism status in a representative sample of the adult population in Spain and the percentage of subjects at guideline-recommended LDL-C goals. Material and methods The di@bet.es study is a national, cross-sectional population-based survey of 5728 adults. Results A total of 4776 subjects were studied. Dyslipidemia was diagnosed in 56.8% of subjects; only 13.2% of subjects were treated with lipid lowering drugs. Lipid abnormalities were found in 56.8% of Spanish adults: 23.3% with high LDL…

Postprandial triglyceridaemia is modulated by insulin resistance but not by grade of obesity in abdominal and morbid obese subjects

Background Obesity is associated with high cardiovascular risk. Postprandial lipidaemia has been associated with cardiovascular disease risk. Our aim was to identify whether anthropometric parameters, insulin resistance (IR) and/or fasting plasma triglycerides may determine postprandial changes in lipoprotein concentrations in abdominal and morbid obese subjects. Methods We have studied 20 non-diabetic, normolipidaemic subjects with abdominal obesity, 20 morbid obese subjects and 20 healthy individuals, that have similar age and gender. In all of them a standardised oral fat load test (OFLT) with unsaturated fat was performed. Results During the OFLT, the postprandial triglycerides response…

Effects of marathon running on plasma total homocysteine concentrations.

Summary Aims There is evidence of an excess of acute cardiovascular (CV) events in marathon runners. High plasma total homocysteine (tHcy) concentrations are a recognised risk factor for CV events. Therefore, we investigated the changes in plasma tHcy concentrations 24 h before and after a marathon race. Methods and results Twenty-two non-professional male athletes, mean age 35.6 (6.6), range 23–49 years, were studied the day before and 24 h after finishing a marathon race. None of the athletes was a carrier of the MTHFR 677TT genotype and no ingestion of supplements of vitamins (B12, B6, folic acid) was allowed. Results Changes in plasma folate and plasma vitamin B12 concentrations were no…

Estudio de receptor anómalo suprarrenal en sujetos con síndrome de Cushing ACTH-independiente e hiperplasia nodular suprarrenal

Resumen Introduccion El sindrome de Cushing ACTH-independiente (SCAI) supone el 15-20% de los casos de sindrome de Cushing, de los cuales Material y metodos Estudio descriptivo multicentrico de una serie de 15 casos de SCAI con hiperplasia nodular suprarrenal (periodo de estudio: 2002-2016). En ellos se hizo el despistaje de receptor anomalo, mediante pruebas de estimulacion, considerando patologico un aumento de cortisol plasmatico ≥ del 25% respecto al valor basal. Resultados De los 15 casos, 13 fueron mujeres, con una edad media al diagnostico de 56,8 anos. En 12 de los 15 casos estudiados se detecto positividad de las pruebas de estimulacion. De ellos, fueron positivos para comida de pr…

Efecto del género y de la obesidad en la lipemia posprandial en sujetos sanos normolipidémicos no diabéticos y sujetos con hiperlipemia familiar combinada

Introduccion Un nuevo metodo basado en la autodeterminacion de trigliceridos (TG) capilares permite un mejor conocimiento de la lipemia posprandial (LP). Los objetivos de nuestro estudio son analizar el efecto del genero y la obesidad sobre la LP valorada por medicion capilar de TG diurnos mediante Accutrend GCT® en sujetos sanos y sujetos con hiperlipemia familiar combinada (HFC). Material y metodos Hemos estudiado a 23 sujetos con HFC no relacionados entre si (10 hombres) y a 45 sujetos (29 hombres) normolipidemicos no diabeticos. Todos ellos realizaron tres perfiles diarios de TG capilares durante una semana. Resultados En los sujetos sanos normolipidemicos no diabeticos encontramos valo…

Oxidative Stress and Chronic Inflammatory State Present in Familial Hypercholesterolemia is Reduced After a Fat Overload Rich in Unsaturated Fatty Acids

Determinantes de la lipemia posprandial medida como perfil diurno de triglicéridos en personas no diabéticas con normolipemia

Fundamento y objetivo: Conocer los determinantes clinicos y biologicos de la lipemia posprandial, medida con la autodeterminacion diurna de trigliceridos en sangre capilar (TGc), en personas sin dislipemia ni diabetes. Pacientes y metodo: Hemos estudiado a 76 personas sanas (45 mujeres premenopausicas) con normolipemia y sin diabetes. La determinacion de los TGc se realizo mediante Accutrend® durante 3 dias en 6 puntos establecidos: ayunas, inmediatamente antes y 3 h despues de comer y de cenar, y antes de acostarse. Se midio el area bajo la curva de TGc (ABC-TGc) como expresion de la lipemia posprandial diurna. Resultados: El ABC-TGc fue significativamente mayor en los varones (26,20 [11,0…

Estudio de los valores plasmáticos de Lp(a) en el defecto familiar de unión de la apo B 100 en una población mediterránea del sur de Europa

Aims: 1) to study lipoprotein (a) (Lp(a)) plasma values in subjects with familial ligand-defective apo B 100 (FDB). Methods: We studied 19 heterozygous FDB subjects (8 males) from 12 families, carriers of R3500Q mutation on apo B gene and 90 controls (34 males). The genetic diagnosis was established with PCR-SSCP analysis and automatic sequencing. In all subjects plasma lipids, apoli-poprotein B and Lp(a) levels were determined with standard procedures. Results: Subjects carriers of R3500Q mutation on apo B gene have significantly higher plasma Lp(a) and log transformed Lp(a) values and prevalence of Lp(a) > 30 cut point for coronary heart disease than controls. Conclusions: Subjects with F…

Increased plasma xanthine oxidase activity is related to nuclear factor kappa beta activation and inflammatory markers in familial combined hyperlipidemia

Abstract Background and aims Xanthine oxidase (XO) has been described as one of the major enzymes producing free radicals in blood. Oxidative stress and inflammatory processes have been implicated in the pathogenesis of endothelial dysfunction and the progression of atherosclerosis but until now, there is little data about the influence of vascular prooxidant systems and inflammation in familial combined hyperlipidemia (FCH). Our goal was to evaluate whether XO activity was altered in FCH and if it was related to the inflammatory process represented by NFkB, IL-6 and hsCRP, and assessing the correlation between XO activity and insulin resistance (IR). Method and results 40 Non-related subje…

Reduced penetrance of autosomal dominant hypercholesterolemia in a high percentage of families: importance of genetic testing in the entire family.

Abstract Background Autosomal dominant hypercholesterolemias (ADHs) are characterised by increased plasma levels of total and LDL cholesterol, predisposing to premature atherosclerosis. ADHs comprise several diseases with undistinguishable phenotype, caused by mutations in different genes: LDLR, APOB and PCSK9. Genetic studies are usually performed in patients with altered cholesterol levels. However, some persons carrying pathogenic mutations are normocholesterolemic and there are no further studies about this subject. We have studied the frequency of families and individuals carrying ADH mutations who do not present the disease in Spanish population. Methods We have analysed genes known t…

Misclassification of subjects with insulin resistance and associated cardiovascular risk factors by homeostasis model assessment index. Utility of a postprandial method based on oral glucose tolerance test

Different methods are available for assessing insulin sensitivity in the fasting state. However, insulin resistance (IR) is initially a postprandial disturbance; and usually, when basal (fasting) disturbance appears, the process has been in progress for some time. Our aim was to investigate if a postprandial measurement, performing an oral glucose tolerance test (OGTT), is more sensitive than fasting values. We wished to identify early IR states in healthy, nonobese individuals and ascertain if this situation was associated with other cardiovascular risk factors. A total of 90 nonobese, nondiabetic, and nonsmoker individuals were studied. They were divided into 3 groups according to IR stat…

Association of C677T polymorphism in MTHFR gene, high homocysteine and low HDL cholesterol plasma values in heterozygous familial hypercholesterolemia.

Aim: to investigate the association of C677T polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene, homocysteine plasma values (Hcy), and plasma HDL cholesterol in heterozy-gous familial hypercholesterolemia (hFH).Methods: One hundred and twenty-five hFH subjects were studied. Plasma lipid, lipoprotein, vitamin B12, folic acid and Hcy values were determined. C677T polymorphism in the MTHFR gene was detected by SSCP-PCR. Genetic diagnosis of FH was determined by a three-step protocol using SSCP-PCR, Southern blot, long PCR and automatic sequencing.Results: We found significant differences in plasma HDL-C (CC 1.39±0.34, CT 1.33±0.39 and TT 1.14±0.26 mmol/L, p=0.028) between th…

Therapeutic inertia in patients with type 2 diabetes treated with non-insulin agents

Abstract Aims To analyze therapeutic inertia in type 2 diabetes (T2D) subjects with suboptimal glycemic control and treated with ≥2 non-insulin antidiabetic agents in a primary care setting. Methods A retrospective study was conducted using electronic medical records from subjects with HbA1c ≥7.0% (≥53 mmol/mol). Therapeutic inertia was defined as the absence of treatment intensification despite suboptimal glycemic control where intensification should have been implemented (HbA1c ≥7.5% [≥58 mmol/mol]). Time to the first intensification with non-insulin antidiabetic agent or insulin and HbA1c values at the time of intensification were evaluated by competing risk analysis. Results 2652 adults…

Estudio de los valores de 8-oxo-7,8-dihidro-2’-desoxiguanosina como marcador de estrés oxidativo del ADN en pacientes con hiperlipemia familiar combinada

Fundamento y objetivo: Comparar los valores de 8-oxo-7,8-dihidro-2'-desoxiguanosina (8-oxo-dG) como marcador de estres oxidativo entre personas sanas y pacientes con hiperlipemia familiar combinada (HFC), modelo de dislipemia mixta con resistencia a la insulina y cardiopatia isquemica precoz, y estudiar su relacion con parametros clinicobiologicos de resistencia a la insulina. Sujetos y metodo: Se ha analizado a 40 pacientes (15 mujeres) no relacionados entre si y diagnosticados de HFC y a 20 sujetos sanos (8 mujeres) normolipemicos y no diabeticos. Se recogieron de forma estandarizada parametros clinicos, antropometricos y bioquimicos: perfil lipidico, glucemia e insulinemia basales y dete…

Familial Combined Hyperlipidemia, Metabolic Syndrome and Cardiovascular Disease

Our aim was to investigate the relationship between metabolic syndrome and cardiovascular disease (i.e., survivors of myocardial infarction) in patients with familial combined hyperlipidemia (FCH). We compared a group of 20 male patients with FCH who had survived a myocardial infarction with two other groups matched for age and body mass index, comprising 20 individuals with FCH who had not had a myocardial infraction and 20 control subjects. Plasma lipid, glucose, and insulin levels were determined. Metabolic syndrome was judged to present on the basis of World Health Organization (WHO) and National Cholesterol Education Program-Adult treatment panel (NCEP-ATPIII) criteria. Differences bet…

Gender differences on oxidative stress markers and complement component C3 plasma values after an oral unsaturated fat load test

Factores asociados con el ingreso hospitalario de pacientes diabéticos con ulceración en el pie

Fundamento Identificar y analizar los factores asociados con el ingreso hospitalario en diabeticos con ulceras en los pies, con el fin de identificar y tratar los pacientes de alto riesgo y evitar su ingreso hospitalario, que es la mayor fuente de gasto sanitario debido al pie diabetico. Sujetos y Metodo Hemos estudiado a 108 diabeticos (59 varones, edad media [DE] 68 [11] anos, 100 con diabetes tipo 2, con 16,4 [10,3] anos de evolucion) que acudieron a la unidad del pie diabetico desde enero 1996 hasta septiembre de 1997 con ulceras en los pies. En la primera visita se recogieron parametros clinicos y bioquimicos de riesgo en un protocolo clinico. Los sujetos fueron seguidos una media de 2…

Hipoglucemia grave y prolongada secundaria a cotrimoxazol en sujeto con factores predisponentes

Los niveles plasmáticos de IL-18 se relacionan con la insulinemia y están modulados por polimorfismos del gen de IL-18

INTRODUCTION Atherosclerosis is an inflammatory chronic disease influenced by multiple factors. Different prospective studies have shown that plasmatic levels of inflammatory markers were related to atherosclerosis and cardiovascular disease. OBJECTIVE To evaluate whether plasmatic levels of interleukin 18 (IL-18) are modulated by SNPs (single nucleotide polymorphisms) of the IL 18 gene and its possible association with insulin levels and other cardiovascular risk factors. METHODS 746 individuals were studied for a period of two years by opportunistic selection in the metropolitan area of Valencia. Parameters of lipid and glucose metabolism were analyzed by standard methodology. IL-18 was m…

Identificación y caracterización del primer español con defecto homocigoto familiar de unión de la apolipoproteína B

Fundamento El defecto familiar de union de la apolipoproteina B-100 (DFB) es una enfermedad hereditaria autosomica dominante debida a mutaciones localizadas en el gen de la apolipoproteina B-100, clinicamente indistinguible de la hipercolesterolemia familiar. Describimos el primer homocigoto espanol para el DFB. Metodos Estudiamos por tecnica de PCR–SSCP la mutacion R3500Q en los familiares de primer y segundo grado de la familia con DFB previamente descrita por nuestro grupo. Ademas, analizamos la actividad del receptor de LDL en un ensayo con LDL conjugada con oro coloidal. Resultados El paciente presenta en ambos alelos la mutacion R3500Q causante de DFB. El estudio de la actividad del r…

Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes mellitus.

Background To examine the association of biochemical markers of risk (plasma Hcy, microalbuminuria, lipoprotein (a)(Lp(a)) and diabetic dyslipidaemia) with the prevalence of diabetic foot ulceration in type 2 diabetic patients. Methods Case/control study conducted in 198 type 2 diabetic patients. 89 patients have foot ulcers and 109 have no foot ulcers (control group), in order to establish ORs for diabetic foot ulceration. In all subjects plasma Hcy, Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, HbA1c and microalbuminuria were measured using standard procedures. Results Plasma Hcy, microalbuminuria, HbA…

Waist to hip ratio as a marker of insulin resistance in healthy subjects

Insuficiencia mitral de etiología desconocida en paciente de 20 años

NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue

Neurotrophin-3 (NT3), through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (especially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 (encoded by NTF3) was present in human re…

Papel de la dislipemia aterogénica en el desarrollo del síndrome metabólico

Fundamento y objetivo Averiguar si el diagnostico de sindrome metabolico (SM) definido por los criterios de la International Diabetes Federation (IDF) en 2005 identifica a un mayor numero de sujetos con dislipemia aterogenica de elevado riesgo cardiovascular que los criterios del National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP-III). Pacientes y metodo Estudiamos a una poblacion de 344 sujetos no diabeticos (158 varones y 186 mujeres), de edades comprendidas entre 20 y 70 anos, seleccionados por un metodo de muestreo simple aleatorio entre los que consultaron durante un ano en un centro de salud en el area metropolitana de Valencia (metodo de busqueda oportunista).…

Autosomal Recessive Hypercholesterolemia

Abstract Background Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. Objectives Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. Methods Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. Results We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years…

Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis

Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR-SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR-SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 1…

Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia.

Eur J Clin Invest 2010; 40 (2): 89–94 Abstract Background  Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. Materials and methods  Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear c…

Differences in clinical and biological characteristics and prevalence of chronic complications related to aging in patients with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease that increases with age. Because of this, and due to its chronic complications, T2DM causes high human, social, and financial costs. In addition, the elderly population with T2DM has a marked clinical heterogeneity. Therefore, our main objective was to analyze the relationship of age with the clinical and biological manifestations of the disease and the prevalence of chronic complications in patients with T2DM.A cross-sectional study of a large population with T2DM (n=405) randomly selected from a Diabetes Unit and 2 health care centers (60%). The clinical, anthropometric, and biochemical variables of the subjects were c…

Oxidative stress and mrna expression after an oral unsaturated fat load test in subjects with abdominal obesity

Establishing cut-off values for apolipoprotein B and non-HDL-C according to LDL-C values in a South European population

SUMMARY Background: Low-density lipoprotein cholesterol (LDL-C) remains the primary target of therapy in most strategies of dyslipidaemia management focused on cardiovascular disease prevention. Different guidelines have identified specific LDL-C cut-off points as targets for therapeutic intervention. Many clinical situations characterised by dyslipidaemia and elevated triglycerides are common in our environment and in overall industrialised countries. Thus, lipid goals based only on LDL-C could misclassify an important percentage of subjects. The objective of the present study was to establish cut-off point values for apoB and non-HDL-C in relation to the identified LDL-C cut-off points fo…

Evaluation of clinical diagnosis criteria of familial ligand defective apoB 100 and lipoprotein phenotype comparison between LDL receptor gene mutations affecting ligand-binding domain and the R3500Q mutation of the apoB gene in patients from a South European population

Familial hypercholesterolemia (FH) and familial defective apoB 100 (FDB) are characterized by increased plasma low-density lipoprotein cholesterol (LDLc) levels and risk of coronary heart disease (CHD). FDB is clinically indistinguishable from FH. The aims of this study were to evaluate clinical diagnosis criteria for FDB and to compare the lipoprotein phenotype between carriers of LDL receptor (LDLR) gene mutations that affect the ligand-binding domain and subjects with the R3500Q mutation in apoB gene. We studied 213 subjects (113 probands) with FH and 19 heterozygous FDB subjects. Genetic diagnosis was determined by following a protocol based on Southern blot and polymerase chain reactio…

Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients.

Context: Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting.Objective: To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state.Design: A commercial liquid preparation of long-chain triglycerides (Supracal®; ω6/ω3 ratio &amp;gt;20/1, OUFL) was administered to 20 patients and 10 age-matched controls. Whole blood was collected before (fasting state) and 4 h after admi…

Polymorphisms in endothelin system genes, arsenic levels and obesity risk.

Background/objectivesObesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity.Subjects/methodsWe analyz…

Cardiovascular autonomic neuropathy in type 1 diabetic patients with and without peripheral neuropathy.

One hundred Type 1 diabetic patients (54 men, 46 women) mean age 28.9 +/- 8.4 years, were selected from among individuals referred to our hospital, with no previous diagnosis of diabetic chronic complications including diabetic neuropathy. After clinical and physical examinations, subjects were divided into two groups: with (n = 37) and without (n = 63) peripheral neuropathy. The percentage of subjects with cardiovascular autonomic neuropathy (AN), diagnosed by positive results to at least two of the five cardiovascular tests (Valsalva ratio, EI ratio, 30/15 ratio, blood-pressure response to standing up and handgrip test), was 40%: 72.9% in the group with peripheral neuropathy and 20.6% in …

Enhanced reduction in oxidative stress and altered glutathione and thioredoxin system response to unsaturated fatty acid load in familial hypercholesterolemia.

Abstract Objectives Familial hypercholesterolemia (FH) is characterized by increased oxidative stress (OS) levels. In the postprandial state, lipids and lipoproteins modulate OS status through their impact on pro-oxidant and antioxidant mechanisms. The objective of this study was to evaluate in patients with FH the response to an unsaturated oral fat load test (OFLT) by analyzing the mRNA levels of genes involved in the glutathione and thioredoxin antioxidant systems. Design and Methods We analyzed 14 FH patients and 20 normolipidemic and normoglycemic controls. In both groups, mRNA values of antioxidant enzyme genes (glutathione and thioredoxin systems) were determined at baseline and at 2…

Utilidad de la ultrasonografía endoscópica para el diagnóstico de localización de tumores neuroendocrinos pancreáticos: presentación de 2 insulinomas benignos

Los insulinomas son tumores neuroendocrinos que se manifiestan por episodios de hipoglucemia de ayuno. El diagnostico se basa en la sospecha clinica, que debe ir seguida de la demostracion de hiperinsulinismo y la localizacion tumoral. Sin embargo, la localizacion no siempre es posible con las tecnicas de imagen habituales, por lo que se debe recurrir a otras mas complejas. Presentamos 2 casos de insulinomas cuya localizacion tumoral no fue posible con tecnicas de imagen convencionales, pero si con ultrasonografia endoscopica.

Association of chemokines IP-10/CXCL10 and I-TAC/CXCL11 with insulin resistance and enhance leukocyte endothelial arrest in obesity

Abstract Background and aims Obesity is a key contributing factor to incidental type 2 diabetes and cardiovascular disease. CXCR3 receptor and its ligands CXCL 10 and 11 are associated with atherosclerosis and cardiovascular disease. The aim of our study was to analyse the role of the CXCR3 ligands on insulin resistance (IR) and endothelial dysfunction in human obesity. Methods and results We have studied 45 obese patients (mean age 44 ± 6 years, body mass index 45 ± 9 kg/m2) who were selected for Roux-Y-gastric bypass surgery and 21 non obese control subjects with similar age and gender distribution. We measured by ELISA the circulating levels of the CXCR3 ligands interferon-γ inducible pr…

Autosomal recessive hypercholesterolemia in Spain.

Abstract Background and aims Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. We aimed to characterize ARH in Spain. Methods Data were collected from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. A literature search was performed up to June 2017, and all diagnostic genetic studies for familial hypercholesterolemia of Spain were reviewed. Results Seven patients with ARH were identified, 6 true homozygous and one compound heterozygous with a novel muta…

Asociación de factores lipídicos, genotipo de APOE y tipos de mutación del gen del receptor de LDL con el infarto agudo de miocardio en sujetos con hipercolesterolemia familiar heterocigota

Fundamento Evaluar la relacion de los lipidos, del genotipo de APOE y del tipo de mutacion delgen del receptor de LDL, clasificandolas en nulas y no nulas, sobre la prevalencia de infartoagudo de miocardio (IAM) en individuos heterocigotos con hipercolesterolemia familiar (HF) delsur de Europa, donde existen pocos datos al respecto. Pacientes y metodo Se trata de un estudio transversal que compara individuos con HF e IAM(n = 32) y a individuos con HF sin IAM (n = 76) mayores de 35 anos (41 varones y 67 mujeres).En 88 sujetos se establecio el diagnostico genetico, siendo divididos en portadores de mutacionesnulas o no nulas del gen del receptor de LDL. Se han comparado los factores clasicosd…

Estándares SEA 2019 para el control global del riesgo cardiovascular

One of the main goals of the Spanish Society of Arteriosclerosis is to contribute to a wider and greater knowledge of vascular disease, its prevention and treatment. Cardiovascular diseases are the leading cause of death in our country and also lead to a high degree of disability and health expenditure. Arteriosclerosis is a multifactorial disease, this is why its prevention requires a global approach that takes into account the different risk factors with which it is associated. Thus, this document summarizes the current level of knowledge and integrates recommendations and procedures to be followed for patients with established cardiovascular disease or high vascular risk. Specifically, t…

Polymorphisms of the UCP2 gene are associated with body fat distribution and risk of abdominal obesity in Spanish population

Eur J Clin Invest 2011 Abstract Background  Increased accumulation of fat results from an imbalance between energy expenditure and intake, being modulated by different environmental and genetic factors. Uncoupling proteins (UCPs) are mitochondrial carrier proteins able to spend energy generating heat. Therefore, variations in these genes are good candidates as potential modulators of body fat accumulation. Our aim was to investigate the possible association of genetic variations of the gene codifying the UCP2 protein with obesity and fat distribution. Design  We performed a cross-sectional study in 2367 individuals from two population-based studies from different regions of Spain. The Horte…

Different impacts of cardiovascular risk factors on oxidative stress.

The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant…

SGLT-2 (Sodium-Glucose Cotransporter 2) Inhibition Reduces Ang II (Angiotensin II)-Induced Dissecting Abdominal Aortic Aneurysm in ApoE (Apolipoprotein E) Knockout Mice.

Objective: Abdominal aortic aneurysm (AAA) is a pathological condition of permanent vessel dilatation that predisposes to the potentially fatal consequence of aortic rupture. SGLT-2 (sodium-glucose cotransporter 2) inhibitors have emerged as powerful pharmacological tools for type 2 diabetes mellitus treatment. Beyond their glucose-lowering effects, recent studies have shown that SGLT-2 inhibitors reduce cardiovascular events and have beneficial effects on several vascular diseases such as atherosclerosis; however, the potential effects of SGLT-2 inhibition on AAA remain unknown. This study evaluates the effect of oral chronic treatment with empagliflozin—an SGLT-2 inhibitor—on dissecting …

Influence of microsomal triglyceride transfer protein promoter polymorphism -493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant disease characterized by elevated levels of low-density lipoprotein-cholesterol (LDL-C). Phenotypic expression is highly variable, being influenced by diet, age, gender, body mass index, apolipoprotein E genotype and type of LDL-receptor gene mutation. Microsomal triglyceride (TG) transfer protein (MTP) is a protein involved in lipid metabolism. Polymorphism MTP -493 GT has been shown to modulate lipid levels in several populations. To analyse the effect of this polymorphism in the lipid phenotype expression of FH and treatment response, we studied a sample of 222 Spanish FH patients, of whom 147 were studied before and after trea…

Activation of the Constitutive Androstane Receptor Inhibits Leukocyte Adhesiveness to Dysfunctional Endothelium

Leukocyte cell recruitment into the vascular subendothelium constitutes an early event in the atherogenic process. As the effect of the constitutive androstane receptor (CAR) on leukocyte recruitment and endothelial dysfunction is poorly understood, this study investigated whether the role of CAR activation can affect this response and the underlying mechanisms involved. Under physiological flow conditions, TNFα-induced endothelial adhesion of human leukocyte cells was concentration-dependently inhibited by preincubation of human umbilical arterial endothelial cells with the selective human CAR ligand CITCO. CAR agonism also prevented TNFα induced VCAM-1 expression, as well as MCP-1/CCL-2 a…

Altered Semmes–Weinstein monofilament test results are associated with oxidative stress markers in type 2 diabetic subjects

Abstract Background Different lines of evidence suggest that oxidative stress (OS) is implicated in the pathogenesis of diabetic neuropathy. The Semmes–Weinstein monofilament (SWM) test is an efficient tool for evaluating diabetic polyneuropathy and diabetic foot. In this study, we analyzed the association between OS markers and altered SWM test results in type 2 diabetes (T2DM) patients. Methods Seventy T2DM patients were studied and 34 showed altered SWM results. The clinical and biochemical parameters were determined using standardized methods. Levels of oxidized glutathione (GSSG) and malondialdehyde (MDA) were measured in circulating mononuclear cells using high-performance liquid chro…

Easy One-Step Amplification and Labeling Procedure for Copy Number Variation Detection.

Abstract Background The specific characteristics of copy number variations (CNVs) require specific methods of detection and characterization. We developed the Easy One-Step Amplification and Labeling procedure for CNV detection (EOSAL-CNV), a new method based on proportional amplification and labeling of amplicons in 1 PCR. Methods We used tailed primers for specific amplification and a pair of labeling probes (only 1 labeled) for amplification and labeling of all amplicons in just 1 reaction. Products were loaded directly onto a capillary DNA sequencer for fragment sizing and quantification. Data obtained could be analyzed by Microsoft Excel spreadsheet or EOSAL-CNV analysis software. We d…

Age-related increase in xanthine oxidase activity in human plasma and rat tissues.

This study assessed the role of xanthine oxidase in vascular ageing. A positive correlation between xanthine oxidase activity and age was found in human plasma. Similar results were found in rat plasma. Xanthine oxidase expression and activity in homogenates from the aortic wall were significantly higher in samples from old rats than in their young counterparts (p<0.01). In rat skeletal muscle homogenates both xanthine oxidase expression and activity showed a similar age-related profile. Superoxide production by xanthine oxidase in aortic rings was higher in aged rats. Uric acid, the final product of xanthine oxidase has been proposed as a risk factor for coronary heart disease and an indep…

Diferencias en las características clínico-biológicas y prevalencia de complicaciones crónicas en relación con el envejecimiento de pacientes con diabetes tipo 2

Resumen La diabetes tipo 2 (DMT2) es una enfermedad con elevada prevalencia que aumenta con la edad. Por este motivo y por sus complicaciones cronicas genera elevado coste humano, social y economico en la poblacion mayor. Ademas, la poblacion mayor con DMT2 presenta una marcada heterogeneidad clinica. Por lo que nuestro objetivo principal es conocer como se relaciona la edad con el fenotipo clinico-biologico y cual es la prevalencia de complicaciones cronicas en el paciente con DMT2. Material y metodos Estudio transversal de una amplia poblacion de DMT2 (n = 405) seleccionada de forma aleatoria de una Unidad de Diabetes y 2 centros de salud (60%). En estos sujetos se recogieron variables cl…

Hypercholesterolemic patients have higher eryptosis and erythrocyte adhesion to human endothelium independently of statin therapy

BACKGROUND Phosphatidylserine (PS) externalization out of the membrane facilitates the eryptotic erythrocytes (EE) binding to endothelial cells (EC), potentially leading to atherosclerosis. Thus, the levels of eryptosis and interactions of EE-EC in hypercholesterolemic patients, either non-medicated or medicated, compared with healthy subjects were studied. METHODS A total of 56 subjects clustered into three groups: (control (n = 20), hypercholesterolemic non-treated (HCNT) (n = 15), and statin-treated (HCT) (n = 21)) were enrolled in this cross-sectional study. Biochemical parameters were determined with validated and standard methods. PS exposure was estimated from annexin-V-binding, cell…

Mitral regurgitation of unknown etiology in a 20-year-old patient

Lipid-free apolipoprotein (apo) A-I is converted into alpha-migrating high density lipoproteins by lipoprotein-depleted plasma of normolipidemic donors and apo A-I-deficient patients but not of Tangier disease patients

Plasma of patients with Tangier disease (TD) is devoid of alpha-LpA-I (apolipoprotein A-I-containing lipoprotein), which in normolipidemic plasma constitutes the majority of high density lipoprotein (HDL). The residual amounts of apolipoprotein A-I (apo A-I) in TD plasma have electrophoretic prebeta1-LpA-I mobility. We have previously demonstrated that TD plasma does not convert prebeta1-LpA-I into alpha-LpA-I. In this study we found that plasmas of normolipidemic controls, apo A-I-deficient patients and patients with fish-eye disease, but not plasmas of six TD patients, convert biotinylated lipid-free apo A-I into alpha-LpA-I. Supplementation of plasma with free oleic acid or fatty acid fr…

Postprandial Changes in Chemokines Related to Early Atherosclerotic Processes in Familial Hypercholesterolemic Subjects: A Preliminary Study.

Familial hypercholesterolemia (FH) is associated with higher levels of inflammatory mediators such as chemokines, which contribute to an increased risk of premature atherosclerosis in these patients. We studied the response of chemokines related to early atherosclerotic processes during an oral unsaturated fat load test (OFLT) in patients with heterozygous FH and compared this response to normolipidemic and normoglycemic subjects.Blood samples were taken from 12 FH patients and 20 healthy controls with a similar age, gender distribution, and body mass index. Plasma chemokine levels were determined in both groups in a fasting state and at 2, 4, 6, and 8 h after an OFLT using human cytokine m…

Anthropometric parameters and permanent remission of comorbidities 10 years after open gastric bypass in a cohort with high prevalence of super-obesity

Abstract Background and aim Roux-en-Y gastric bypass (RYGB) is an effective treatment for weight loss in patients with morbid obesity. However, few studies have assessed its long-term efficacy in super-obese patients. The study objective was to analyse the long-term effectiveness of RYGB and its effect on improvement of comorbidities after 10 years of follow-up, and to compare the results depending on baseline BMI ( 2 vs ≥50 kg/m 2 ). Patients and methods A retrospective study was conducted in 63 patients referred for RYGB with a 10-year or longer follow-up period. Mean BMI before surgery was 55 kg/m 2 . Results Mean BMI decreased to 38.1 kg/m 2 at 10 years of follow-up. The success rates a…

Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients

Abstract HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin + laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each interventi…

Severe, long-term hypoglycemia induced by co-trimoxazole in a patient with predisposing factors

Influencia de las mutaciones HF Valencia 1 y 2 del gen del receptor de LDL sobre la respuesta terapéutica a simvastatina en sujetos con hipercolesterolemia familiar heterocigota caracterizada molecularmente

Fundamento Analizar si el diagnostico molecular de la hipercolesterolemia familiar (HF) ayuda apredecir la respuesta terapeutica a simvastatina, en una poblacion mediterranea del sur de Europa. Sujetos y metodo Hemos estudiado la respuesta terapeutica en 27 sujetos con diagnostico genetico de HF (11 varones) pertenecientes a 8 familias con HF, seleccionadas por muestreo aleatorio entre 30 familias con HF con diagnostico molecular, en un estudio de intervencion sin grupo control con 20 mg/dia de simvastatina. Comparamos las caracteristicas clinicobiologicas entre sujetos clasificados como HF mutaciones nulas (HF Valencia 1 y Valencia 2; n = 11) o HF mutaciones no nulas (n = 16) en situacion …

Insulin resistance and oxidative stress in familial combined hyperlipidemia.

Oxidative stress is associated with atherosclerosis. Familial combined hyperlipidemia (FCH) is considered as a human model of primary dyslipidemia and atherosclerosis frequently associated with insulin resistance (IR), but there are few data on its possible relation to oxidative stress. The objective of this study was to evaluate oxidative stress status using different markers in subjects with FCH assessing its possible correlation with anthropometric parameters and IR. This was a cross-sectional study. A cohort of 40 FCH patients (20 with IR (HOMAor=3.2) and 20 without IR (HOMA3.2)), and 20 healthy volunteers were included, all of them non-diabetic, normotensive and non-smokers. We measure…

Lipoprotein phenotype and insulin resistance in familial combined hyperlipidemia.

The study objective was to investigate the relationship of insulin resistance (IR) with the lipoprotein phenotype in familial combined hyperlipidemia (FCH). Thirty-seven FCH men diagnosed by clinical and biochemical criteria and classified as lipoprotein phenotype IIa (n = 9), IIb (n = 17), or IV (n = 11) were compared with a healthy control group of 30 men of similar age, body mass index (BMI), waist to hip ratio (WHR), and systolic and diastolic blood pressure. In all subjects, the plasma lipoprotein profile and baseline and post-oral glucose tolerance test (OGTT) glucose and insulin plasma values were measured. An intravenous glucose tolerance test was performed and IR was studied by the…

Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes

Background Type 1 diabetes mellitus (T1DM) patients display increased risk of cardiovascular disease (CVD) and are characterized by a diminished regulatory T (Treg) cell content or function. Previous studies have shown an association between decreased CDKN2A/2B/2BAS gene expression and enhanced CVD. In the present study the potential relationship between CDKN2A/2B/2BAS gene expression, immune cell dysfunction and increased cardiovascular risk in T1DM patients was explored. Methods A cross-sectional study was performed in 90 subjects divided into controls and T1DM patients. Circulating leukocyte subpopulations analysis by flow cytometry, expression studies on peripheral blood mononuclear cel…

The influence of apo E phenotypes on the plasma triglycerides response to hormonal replacement therapy during the menopause

Objective: To study the influence of apo E phenotype in plasma lipids, especially in triglycerides levels, in menopausal women receiving hormonal replacement therapy (HRT). Methods: One hundred and ten postmenopausal women were studied. Plasma total cholesterol (TC), HDL-C and triglycerides (TG) were measured before and after 3 months of HRT and the apo E phenotype was determined. According to the apo E phenotype the sample was divided into three groups: E2/E3 (n=28), E3/E3 (n=96) and E4/E3 (n=25). Results: In the pre-treatment state, higher plasma levels of TC and TC/HDL-C ratio were observed in women with phenotype E3/E4 (P<0.0001 and P<0.02, respectively), while higher plasma TG levels w…

Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation.

Primary hypercholesterolemia (PH) is associated with a low grade systemic inflammation that is likely the main driver of premature atherosclerosis. Accordingly, we characterized the immune cell behaviour in PH and its potential consequences. Whole blood from 22 PH patients and 21 age-matched controls was analysed by flow cytometry to determine the percentage of leukocyte immunophenotypes, activation, and platelet-leukocyte aggregates. Plasma markers were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The adhesion of platelet-leukocyte aggregates to tumor necrosis factor-&alpha

Abdominal obesity, insulin resistance, and metabolic syndrome in a southern European population.

Background: Our objective was to investigate the relationship between abdominal obesity (AO), as measured by waist circumference (WC), insulin resistance (IR), and components of the metabolic syndrome (MS). Methods: A cross-sectional study was carried out with 283 subjects (130 males and 153 females aged 25–65 years) from a primary care outpatient clinic in Valencia (Spain) over a period of 1 year. Body mass index (BMI), waist circumference (WC), blood pressure (BP), total cholesterol, triglycerides, HDL-C, glucose, and insulin were measured by standard methods. IR was defined as HOMA-IR equal to or greater than 3.8. Results: The prevalence of IR was 39.6%. Subjects were divided into groups…

Association of selected ABC gene family single nucleotide polymorphisms with postprandial lipoproteins: results from the population-based Hortega study.

The aim of the study was to determine the influence of twenty single nucleotide polymorphisms (SNPs) of the ABCA1, ABCG1, ABCG5 and ABCG8 genes on the plasmatic concentrations of total cholesterol (TC), HDL and LDL cholesterol (HDLc, LDLc) in the postprandial state with a representative Spanish Caucasian population (1473 individuals, 50.0% women, ages ranging 21-85 years). In men, subjects with the AA genotype of the ABCA1 rs2230806 (R219K) polymorphism were associated with increased plasma LDLc levels, while the ABCA1 haplotype, which included the rs2230806 A allele, was associated with higher TC and LDLc plasma concentrations. In women, significant relationships were found between rs18935…

Functional role of endothelial CXCL16/CXCR6-platelet-leucocyte axis in angiotensin II-associated metabolic disorders.

Aims Angiotensin-II (Ang-II) is the main effector peptide of the renin-angiotensin system (RAS) and promotes leucocyte adhesion to the stimulated endothelium. Because RAS activation and Ang-II signalling are implicated in metabolic syndrome (MS) and abdominal aortic aneurysm (AAA), we investigated the effect of Ang-II on CXCL16 arterial expression, the underlying mechanisms, and the functional role of the CXCL16/CXCR6 axis in these cardiometabolic disorders. Methods and results Results from in vitro chamber assays revealed that CXCL16 neutralization significantly inhibited mononuclear leucocyte adhesion to arterial but not to venous endothelial cells. Flow cytometry and immunofluorescence s…

Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX3CL1/CX3CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion

Background: Metabolic syndrome is associated with low-grade systemic inflammation, which is a key driver of premature atherosclerosis. We characterized immune cell behavior in metabolic syndrome, its consequences, and the potential involvement of the CX3CL1/CX3CR1 and CCL2/CCR2 chemokine axes. Methods: Whole blood from 18 patients with metabolic syndrome and 21 age-matched controls was analyzed by flow cytometry to determine the leukocyte immunophenotypes, activation, platelet-leukocyte aggregates, and CX3CR1 expression. ELISA determined the plasma marker levels. Platelet-leukocyte aggregates adhesion to tumor necrosis factor-&alpha

Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages

The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet-fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM…

Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I

Plasmas of patients with Tangier disease (TD) lack lipid-rich α-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free preβ-HDL. By contrast to normal plasma, TD plasma does not convert preβ-HDL into α-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of preβ-HDL into α-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both …

Síndrome de apnea-hipopnea del sueño como causa de seudofeocromocitoma

Los feocromocitomas son tumores neuroendocrinos poco frecuentes cuya manifestacion mas caracteristica es la hipertension arterial. Su diagnostico se basa en la demostracion de un exceso de produccion de catecolaminas o de sus metabolitos, seguido de tecnicas de imagen para la localizacion tumoral. Sin embargo, hay situaciones en las que estas hormonas pueden estar elevadas sin que haya un feocromocitoma; por tanto, esto se trata de falsos positivos. En esos casos hablamos de seudofeocromocitoma. Presentamos el caso de un paciente con un nodulo suprarrenal y catecolaminas elevadas de forma repetida en orina de 24 h. Fue intervenido quirurgicamente, pero a pesar de ello persistian las alterac…

Hipertiroidismo en el anciano

. Ademas, existe cierta tendencia a infrautilizar los recursos terapeuticos y preventivos en los ancianos. Las enfermedades tiroideas son muy prevalentes en el anciano, pero su diagnostico y tratamiento difiere de los estandares establecidos en la poblacion de mediana edad 5 , debido a las modificaciones que se producen con el envejecimiento, que conducen a cambios morfologicos y funcionales del tiroides que dificultan la interpretacion de las pruebas diagnosticas. A estos cambios se unen las alteraciones que sobre la funcion tiroidea tienen otras enfermedades intercurrentes, no tiroideas, muy frecuentes entre los ancianos, y las interacciones farmacologicas. Ademas, en el anciano debemos t…

Srebf2 Locus Overexpression Reduces Body Weight, Total Cholesterol and Glucose Levels in Mice Fed with Two Different Diets

Macronutrients represent risk factors for hyperlipidemia or diabetes. Lipid alterations and type 2 diabetes mellitus are global health problems. Overexpression of sterol regulatory element-binding factor (Srebf2) in transgenic animals is linked to elevated cholesterol levels and diabetes development. We investigated the impact of increased Srebf2 locus expression and the effects of control and high-fat, high-sucrose (HFHS) diets on body weight, glucose and lipid metabolisms in transgenic mice (S-mice). Wild type (WT) and S-mice were fed with both diets for 16 weeks. Plasma glucose, insulin and lipids were assessed (n = 25). Immunostainings were performed in liver, pancreas and fat (N = 10).…

PAI-1 Levels are Related to Insulin Resistance and Carotid Atherosclerosis in Subjects with Familial Combined Hyperlipidemia

Familial combined hyperlipidemia (FCH) is a primary atherogenic dyslipidemia with insulin resistance and increased cardiovascular risk. Plasminogen activator inhibitor type 1 (PAI-1) and myeloperoxidase (MPO) activity are associated with proinflammatory and atherothrombotic risk. Our aim was to study the role played by PAI-1 and MPO activity in the carotid atherosclerosis prevalence in FCH subjects. 36 FCH unrelated subjects (17 women) were matched by age and body weight with 36 healthy normolipidemic subjects (19 female). Blood lipids, glucose, insulin, insulin resistance (homeostasis model assessment (HOMA)), MPO, and PAI-1 were determined in both groups. Carotid intima media thickness (…

Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: Study in two Spanish populations

Abstract Background ABCG1 mediates cellular cholesterol transport, but there is very little known about the influence of ABCG1 polymorphisms on human plasma lipoprotein cholesterol concentrations or on the interactions of these polymorphisms with diet. Objective Our objective was to investigate whether interactions between PUFA intake and ABCG1 polymorphisms modulate associations with plasma total cholesterol (TC), LDL- and HDL-cholesterol in two Spanish populations. Methods We grounded our investigation on two general population-based studies: the Hortega study (population A) and the Pizarra study (population B). Participants included 1178 individuals (50.0% women, age range 21–85 years) a…

Increased oxidative stress levels and normal antioxidant enzyme activity in circulating mononuclear cells from patients of familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a clinical condition with high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis, but no data are available on levels of OS and antioxidant enzyme activity in circulating mononuclear cells (CMCs) from FH patients. Circulating mononuclear cells are important mediators in atherosclerosis development, and chronically increased blood OS present in FH can induce modification in CMC activity. The objective of the study was to analyze the OS levels in CMCs from FH patients and controls. We have selected 30 nonrelated FH index patients and 30 normoglycemic and normocholesterolemic controls matched b…

Changes in CDKN2A/2B expression associate with T-cell phenotype modulation in atherosclerosis and type 2 diabetes mellitus.

Previous studies indicate a role of CDKN2A/2B/2BAS genes in atherosclerosis and type 2 diabetes mellitus (T2DM). Progression of these diseases is accompanied by T-cell imbalance and chronic inflammation. Our main objective was to investigate a potential association between CDKN2A/2B/2BAS gene expression and T cell phenotype in T2DM and coronary artery disease (CAD) in humans, and to explore the therapeutic potential of these genes to restore immune cell homeostasis and disease progression. Reduced mRNA levels of CDKN2A (p16Ink4a), CDKN2B (p15Ink4b), and CDKN2BAS were observed in human T2DM and T2DM-CAD subjects compared with controls. Protein levels of p16Ink4a and p15Ink4b were also dimini…

Dificultad en el tratamiento del hipertiroidismo por amiodarona: Presentación de un caso

La amiodarona puede alterar la función tiroidea en un 15-20% de los pacientes que la toman, dando lugar a hipotiroidismo o hipertiroidismo. La sobrecarga de yodo y la toxicidad directa sobre el tiroides inducida por amiodarona pueden provocar hipertiroidismo. Describimos un caso de tirotoxicosis grave por amiodarona que se diagnosticó buscando la causa que descompensó la cardiopatía de base del paciente, condicionando ésta el pronóstico y el manejo terapéutico. El tratamiento precisó un estrecho seguimiento y se basó en dosis elevadas de propiltiouracilo y dexametasona que no controlaron las consecuencias del hipertiroidismo a nivel cardiaco necesitando la tiroidectomia total. Creemos, con …

Hiperlipidemia familiar combinada, síndrome metabólico y enfermedad cardiovascular

Se estudia la relacion entre sindrome metabolico (SM) e infarto agudo de miocardio (IAM) en la hiperlipidemia familiar combinada (HFC). Se comparan 20 sujetos varones con HFC supervivientes a IAM con otras 2 series de sujetos emparejados por edad e indice de masa corporal (IMC): 20 individuos con HFC que no han presentado IAM y 20 controles sanos. Se determinaron los lipidos, la glucosa y la insulina en plasma y la presencia de SM definido por criterios de la Organizacion Mundial de la Salud (OMS) y National Cholesterol Education Program-Adults Treatment Panel (NCEP-ATP-III). El SM definido por criterios OMS se encontro en 19 sujetos con HFC e IAM, en 11 sujetos con HFC sin IAM y en 6 contr…

Insulin resistance in patients with familial combined hyperlipidemia and coronary artery disease.

The minimum model modified by the administration of insulin provides an objective and relatively easily measured index of peripheral sensitivity to insulin which was significantly lower (p <0.02) in familial combined hyperlipidemia (FCH) with ischemic heart disease (IHD) than in FCH without IHD and in control subjects (1.2 +/- 0.6, 1.9 +/- 1.0, 2.9 +/- 1.2 x 10(-4) mU/L/ min, respectively). In patients with FCH, insulin resistance explains, at least in part, their metabolic alterations (hypertension, abnormal glucose tolerance, hyperinsulinemia) and elevated IHD.

Study of abnormal adrenal receptors in subjects with ACTH-independent Cushing's syndrome and nodular adrenal hyperplasia

ACTH-independent Cushing's Syndrome (AICS) accounts for 15-20% of cases of Cushing's syndrome, with1% due to abnormal receptors. Our aim is to study the presence of abnormal receptors in subjects diagnosed with AICS with nodular adrenal hyperplasia in a 14-year period (2002-2016), as well as its clinical-biological and evolutive characteristics.A multicentre descriptive study of a 15-case series of AICS with nodular adrenal hyperplasia (study period: 2002-2016). In these cases, abnormal receptor screening was performed by means of stimulation tests, with a plasma cortisol increase of ≥ 25% from baseline being considered pathologic.Of the 15 cases, 13 were female, with a mean age at diagnosi…

Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism.

OBJECTIVE—To identify a reliable yet simple indirect method for detection of insulin resistance (IR). RESEARCH DESIGN AND METHODS—A total of 65 subjects (44 men and 21 women aged 30–60 years) were selected by a simple random sampling method. Inclusion criteria were voluntary participation from staff and hospital personnel, absence of abnormal glucose tolerance, and normal results of lipid profile and basic blood chemistry. A blood sample was taken after a 12-h overnight fast to determine plasma lipid, glucose, and insulin levels. An intravenous glucose tolerance test with administration of insulin after 20 min and extraction of multiple blood samples for glucose and insulin measurements and…

Plasma homocysteine levels are independently associated with the severity of peripheral polyneuropathy in type 2 diabetic subjects.

Peripheral polyneuropathy (PN) is a frequent complication of diabetes. However, mechanisms underlying the development of PN are multifactorial and not well understood. Our aim was to examine the association of plasma homocysteine (Hcy) with the prevalence and grade of peripheral PN in patients with type 2 diabetes (T2DM). We studied a cohort of 196 subjects with T2DM classified according to the grade of PN (Neuropathy Disability Score, NDS). Subjects with the highest grade of PN were older and had significantly increased levels of creatinine, microalbuminuria, HbA1c, and plasma Hcy compared to the other two groups. The differences in plasma Hcy values were maintained after correcting for co…

A new PCSK9 gene promoter variant affects gene expression and causes autosomal dominant hypercholesterolemia.

Autosomal dominant hypercholesterolemia (ADH) is a genetic disorder characterized by increased low-density lipoprotein (LDL)-cholesterol levels, leading to high risk of premature cardiovascular disease. More than 900 mutations in LDL receptor, six in APOB and 10 in PCSK9 have been identified as a cause of the disease in different populations. All known mutations in PCSK9 causing hypercholesterolemia produce an increase in the enzymatic activity of this protease. Up to now, there are data about the implication of PCSK9 in ADH in a low number of populations, not including a Spanish population.The objective of the study was to study the prevalence of PCSK9 mutations in ADH Spanish population.W…

Unsaturated Oral Fat Load Test Improves Glycemia, Insulinemia and Oxidative Stress Status in Nondiabetic Subjects with Abdominal Obesity.

Aims To evaluate the changes in glycemia, insulinemia, and oxidative stress markers during an oral fat load test in nondiabetic subjects with abdominal obesity and to analyze the association between postprandial oxidative stress markers and postprandial glucose and insulin responses. Methods We included 20 subjects with abdominal obesity (waist circumference > 102 cm for men and > 88 cm for women) and 20 healthy lean controls (waist circumference < 102 cm for men and < 88 cm for women). After 12 hours of fasting we performed a standardized fat load test (0–8 hours) with supracal® (50 g/m2). We determined metabolic parameters, oxidized and reduced glutathione, and malondialdehyde. Results In…

Arteriosclerosis carotídea subclínica en pacientes con hiperlipidemia familiar combinada. Evolución tras dos años de tratamiento con dosis altas de atorvastatina

Resumen Fundamento y objetivo La hiperlipidemia familiar combinada (HFC) es un modelo genetico de dislipidemia aterogenica con insulinorresistencia y cardiopatia isquemica precoz. Nuestro objetivo fue evaluar la presencia de alteraciones a nivel carotideo, como marcador de arteriosclerosis sistemica, en sujetos con HFC, y valorar el efecto del tratamiento con 80 mg de atorvastatina diarios durante 2 anos sobre el grosor de la placa de ateroma. Sujetos y metodos Estudiamos 100 sujetos con HFC sin diabetes en prevencion primaria reclutados consecutivamente. Se determinaron parametros clinicos y bioquimicos, y se realizo ecografia carotidea. En los sujetos con placa de ateroma se inicio tratam…

Importance of HDL cholesterol levels and the total/ HDL cholesterol ratio as a risk factor for coronary heart disease in molecularly defined heterozygous familial hypercholesterolaemia

Aims To assess the relationship of the lipid profile to coronary heart disease in a group of heterozygous familial hypercholesterolaemic subjects with similar age, sex, body mass index, prevalence of angiotensin converting enzyme DD genotype and type of low density lipoprotein receptor mutation. Methods and Results A total of 66 molecularly defined heterozygous familial hypercholesterolaemic subjects, 33 of whom had coronary heart disease, were studied. Clinical features, cardiovascular risk factors and lipid parameters were compared in both groups. Familial hypercholesterolaemic patients with coronary heart disease showed significantly lower values of mean plasma HDL cholesterol and a high…