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, normotensive and nonsmokers. We measured lipid profile, glucose and insulin levels in plasma, and markers of oxidative stress and inflammation such as oxidized glutathione (GSSG), reduced glutathione (GSH) and TRX. RESULTS: Familial combined hyperlipidaemia subjects showed significantly higher levels of GSSG, GSSG/GSH ratio and TRX than controls. In addition, FCH individuals with IR showed the worst profile of oxidative stress status compared to controls and FCH patients without IR (P < 0·01). TRX levels correlated with higher insulin resistance. CONCLUSION: Familial combined hyperlipidaemia patients showed increased TRX levels. TRX was positively correlated with IR. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.

Correlación entre las concentraciones plasmáticas de homocisteína y la polineuropatía diabética evaluada con la prueba del monofilamento de Semmes-Weinstein en pacientes con diabetes tipo 2 / Correlation between plasma concentrations of homocysteine and diabetic polyneuropathy evaluated with the Semmes-Weinstein monofilament test in patients with type 2 diabetes mellitus

Fundamento y objetivo: No se conocen bien potenciales factores de riesgo bioquímicos relacionados con la presencia y progresión de la polineuropatía diabética (PND). Material y método: Hemos estudiado en 405 diabéticos tipo 2 (169 mujeres) la asociación de las concentraciones plasmáticas de homocisteína con la PND evaluada con la prueba del monofilamento de Semmes-Weinstein (SW). Se consideró prueba alterada una puntuación menor o igual de 4, y normal, puntuaciones de 5 y 6. La medición de la homocisteína plasmática, la vitamina B12 y el ácido fólico se hizo con método estandarizado (enzimoinmunoanálisis). Resultados: Los pacientes con diabetes tipo 2 (DM2) con PND evaluada por prueba alterada del monofilamento presentaron de forma estadísticamente significativa mayor edad, tiempo de evolución de la enfermedad y hemoglobina glucosilada (HbA1c), y menor aclaramiento de creatinina. Además, este grupo presentó de forma significativa e independiente mayores valores plasmáticos de homocisteína (media [DE] de 13,64 [4,93] frente a 12,22 [4,48] μmol/l, p < 0,01), con valores similares de vitamina B12 y ácido fólico al comparar ambos grupos. Conclusión: La homocisteína plasmática y la HbA1c son los factores biológicos independientes y modificables que se asociaron con la presencia de PND evaluada con la prueba del monofilamento de SW (AU)

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[Correlation between plasma concentrations of homocysteine and diabetic polyneuropathy evaluated with the Semmes-Weinstein monofilament test in patients with type 2 diabetes mellitus]. / Correlación entre las concentraciones plasmáticas de homocisteína y la polineuropatía diabética evaluada con la prueba del monofilamento de Semmes-Weinstein en pacientes con diabetes tipo 2.

BACKGROUND AND OBJECTIVE: Few modifiable risk factors are known to be associated with the presence and progression of diabetic polyneuropathy (DPN). MATERIAL AND METHOD: We have analyzed in 405 type 2 diabetic (T2DM) subjects (169 women) the association of plasma homocysteine with the presence of DPN measured with the Semmes-Weinstein (SW) monofilament test. A score below 4 was considered an altered SW monofilament test. Plasma homocysteine, vitamin B12 and folic acid were measured using standard procedures (ELISA). RESULTS: Patients with T2DM with altered SW test have significantly higher age, evolution of disease, HbA1c and lower creatinine clearance values. In addition, plasma homocysteine values were independently and significantly higher in T2DM with DPN measured as altered SW test (13.64 ± 4.93 vs. 12.22 ± 4.48 µmol/l, P<.01) with similar vitamin B12 and folic acid values comparing the 2 groups. CONCLUSION: Plasma homocysteine and HbA1c values are the 2 modifiable biological factors associated with the presence of DPN evaluated as an altered SW monofilament test in T2DM subjects.

Arteriosclerosis carotídea subclínica en pacientes con hiperlipidemia familiar combinada. Evolución tras dos años de tratamiento con dosis altas de atorvastatina / Subclinical carotid atherosclerosis in patients with familial combined hyperlipidemia. Two years follow-up after treatment with high doses of atorvastatin

Fundamento y objetivo: La hiperlipidemia familiar combinada (HFC) es un modelo genético de dislipidemia aterogénica con insulinorresistencia y cardiopatía isquémica precoz. Nuestro objetivo fue evaluar la presencia de alteraciones a nivel carotídeo, como marcador de arteriosclerosis sistémica, en sujetos con HFC, y valorar el efecto del tratamiento con 80mg de atorvastatina diarios durante 2 años sobre el grosor de la placa de ateroma. Sujetos y métodos: Estudiamos 100 sujetos con HFC sin diabetes en prevención primaria reclutados consecutivamente. Se determinaron parámetros clínicos y bioquímicos, y se realizó ecografía carotídea. En los sujetos con placa de ateroma se inició tratamiento con 80mg de atorvastatina durante 2 años.Resultados: El 29% de los pacientes presentaban placa de ateroma. No encontramos diferencias significativas entre los sujetos con y sin placa de ateroma en ninguno de los parámetros que permitiera predecir qué sujetos con HFC serían susceptibles de desarrollar arteriosclerosis subclínica. Veinte sujetos con placa de ateroma aceptaron participar en el estudio de intervención. Tras 2 años hubo una reducción significativa de las cifras de cLDL (30%) y del grosor de la placa de ateroma (10%).Discusión: La ecografía carotídea es útil para detectar arteriosclerosis subclínica en pacientes de alto riesgo cardiovascular como son los sujetos con HFC. Además, el tratamiento con dosis elevadas de atorvastatina induce una regresión de la placa de ateroma mantenida tras 2 años de tratamiento. Nuestros datos sugieren que el tratamiento intensivo con atorvastatina podría ser beneficioso para reducir el desarrollo de enfermedad cardiovascular en este grupo de pacientes (AU)

Background and objective: Familial combined hyperlipidemia (FCH) is a genetic model of atherogenic dyslipidemia with insulin resistance and early coronary disease. Our objective was to evaluate the presence of carotid alterations as a marker of systemic atherosclerosis in subjects with FCH and assess the effect of 80mg of atorvastatin per day in carotid plaque thickness after 2years. Subjects and methods:100 non diabetic subjects with FCH in primary prevention were consecutively included. Clinical and biochemical parameters and carotid ultrasonography were performed. Subjects with carotid plaque started treatment with 80mg of atorvastatin per day for 2years. Results: 29% of subjects had carotid plaques. We did not find significant differences in any of the parameters between subjects with presence or absence of carotid plaques. Twenty subjects with carotid plaques accepted/agreed to participate in the interventional study. Two years follow-up showed a significant reduction in LDLc (30%) and carotid plaque thickness (10%). Conclusion:Carotid ultrasonography is useful to detect subclinical atherosclerosis in high risk cardiovascular patients such as subjects with FCH. Treatment with high doses of atorvastatin induces the regression of carotid plaque thickness after 2years follow-up. Our results suggest that intensive treatment with atorvastatin could be useful to reduce the development of cardiovascular disease in this group of patients (AU)

[Subclinical carotid atherosclerosis in patients with familial combined hyperlipidemia. Two years follow-up after treatment with high doses of atorvastatin]. / Arteriosclerosis carotídea subclínica en pacientes con hiperlipidemia familiar combinada. Evolución tras dos años de tratamiento con dosis altas de atorvastatina.

BACKGROUND AND OBJECTIVE: Familial combined hyperlipidemia (FCH) is a genetic model of atherogenic dyslipidemia with insulin resistance and early coronary disease. Our objective was to evaluate the presence of carotid alterations as a marker of systemic atherosclerosis in subjects with FCH and assess the effect of 80 mg of atorvastatin per day in carotid plaque thickness after 2 years. SUBJECTS AND METHODS: 100 non diabetic subjects with FCH in primary prevention were consecutively included. Clinical and biochemical parameters and carotid ultrasonography were performed. Subjects with carotid plaque started treatment with 80 mg of atorvastatin per day for 2 years. RESULTS: 29% of subjects had carotid plaques. We did not find significant differences in any of the parameters between subjects with presence or absence of carotid plaques. Twenty subjects with carotid plaques accepted/agreed to participate in the interventional study. Two years follow-up showed a significant reduction in LDLc (30%) and carotid plaque thickness (10%). CONCLUSION: Carotid ultrasonography is useful to detect subclinical atherosclerosis in high risk cardiovascular patients such as subjects with FCH. Treatment with high doses of atorvastatin induces the regression of carotid plaque thickness after 2 years follow-up. Our results suggest that intensive treatment with atorvastatin could be useful to reduce the development of cardiovascular disease in this group of patients.

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 state--group 1: non-IR--homeostasis model assessment of IR (HOMA(IR)) and insulin sensitivity index of Matsuda-De Fronzo (ISI-Mat) were normal (HOMA(IR) <3.2 and ISI-Mat >4.0); group 2: with IR post-OGTT (ISI-Mat ≤4.0 and HOMA(IR) <3.2); and group 3: subjects with IR in basal conditions (HOMA(IR) ≥3.2). An intravenous glucose tolerance test to compare both indices was also performed. In 14.4% of subjects, the fasting HOMA(IR) values failed to identify IR (false-negative results). The ISI-Mat values were better correlated than HOMA(IR) (r = 0.875, P = .0001 and r = -0.631, P = .0001, respectively) with insulin sensitivity index obtained with intravenous glucose tolerance test. Subjects with IR had higher prevalence of a cluster of cardiovascular risk factors than non-IR subjects. These data show that that a significant percentage of subjects were misclassified with HOMA(IR). Early identification of IR by OGTT was associated with other cardiovascular risk factors. The OGTT is a simple method that could be applied to accurately identify IR subjects in the general population.

Classical cardiovascular risk factors according to fasting plasma glucose levels.

BACKGROUND: To compare the prevalence of classical cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) in our population according to fasting plasma glucose levels (FPG). METHODS: 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 FPG < 5.6 mmol/L; FPG between 5.6 and 6.0 mmol/L (FPG1); FPG between 6.1-6.9 mmol/L (FPG2); and diabetes (DM) FPG > or = 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) were analyzed. RESULTS: Subjects with FPG2 have a prevalence of classic CVRF and MetS similar to that observed in subjects with type 2 diabetes mellitus (T2DM). The TC:HDL-C index > or = 5 in 56% and 57%, Apo B > or = 1.2 g/L in 59% and 57%, hypertension in 60% and 54% of FPG2 and T2DM subjects, respectively. MetS was diagnosed in 79% of FPG2 and 80% of T2DM. We found significant differences with FPG1 group who presented low CVRF and MetS proportion. CONCLUSION: In our population FPG2 and T2DM subjects show a similar cardiovascular risk profile. On the other hand, such risk is significantly lower in subjects with FPG between 5.6-6.0 mmol/L. These results might have practical implications.

[Familial combined hyperlipidemia, metabolic syndrome and cardiovascular disease]. / Hiperlipidemia familiar combinada, síndrome metabólico y enfermedad cardiovascular.

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 between the groups were evaluated using non-parametric tests and the association between ischemic coronary disease and other parameters was assessed by logistic regression analysis. According to WHO criteria, the metabolic syndrome was present in 19 FCH patients who had survived a myocardial infarction, in 11 individuals with FCH who had not had a myocardial infraction, and in six control subject (P<.001); the difference between FCH patients with and without myocardial infarction was significant (P<.01). Presence of the metabolic syndrome, as defined by WHO criteria, is a marker of cardiovascular risk in individuals with FCH.

Hiperlipidemia familiar combinada, síndrome metabólico y enfermedad cardiovascular / Familial combined hyperlipidemia, metabolic syndrome and cardiovascular disease

Se estudia la relación entre síndrome metabólico (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 índice de masa corporal (IMC): 20 individuos con HFC que no han presentado IAM y 20 controles sanos. Se determinaron los lípidos, la glucosa y la insulina en plasma y la presencia de SM definido por criterios de la Organización Mundial de la Salud (OMS) y National Cholesterol Education Program-Adults Treatment Panel (NCEP-ATP-III). El SM definido por criterios OMS se encontró en 19 sujetos con HFC e IAM, en 11 sujetos con HFC sin IAM y en 6 controles (p < 0,001); hubo diferencias significativas (p < 0,01) al comparar los sujetos con HFC con y sin IAM. No hubo diferencias significativas entre grupos de HFC al estudiar el SM por criterios ATP-III. La HFC es una dislipidemia primaria frecuentemente asociada con resistencia a la insulina y elevado riesgo cardiovascular. En los sujetos con HFC, la presencia de SM según criterios de la OMS es un marcador de riesgo cardiovascular

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 between the groups were evaluated using non-parametric tests and the association between ischemic coronary disease and other parameters was assessed by logistic regression analysis. According to WHO criteria, the metabolic syndrome was present in 19 FCH patients who had survived a myocardial infarction, in 11 individuals with FCH who had not had a myocardial infraction, and in six control subject (P<.001); the difference between FCH patients with and without myocardial infarction was significant (P<.01). Presence of the metabolic syndrome, as defined by WHO criteria, is a marker of cardiovascular risk in individuals with FCH

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 calculation of the minimal model approximation of the metabolism of glucose (MMAMG) S(i) value were performed. Three indirect indexes used to predict insulin sensitivity or IR were calculated, and metabolic syndrome was diagnosed using the Adult Treatment Panel III (ATP III) criteria. All results were correlated with those of the MMAMG. RESULTS: The 75th percentile value as the cutoff point to define IR corresponded with a fasting plasma glucose level of 12 mU/l, a homeostasis model assessment of 2.6, a 25th percentile for S(i) value of 21, and QUICKI (quantitative insulin sensitivity check index) and McAuley indexes of 0.33 and 5.8, respectively. The S(i) index correlated (P < 0.001) with all the indirect indexes and parameters of the metabolic syndrome. CONCLUSIONS: When compared with the S(i) index, the most sensitive and specific indirect method was the score proposed by McAuley et al. (specificity 0.91, sensitivity 0.75, 9.2 probability ratio of a positive test), followed by the existence of metabolic syndrome (specificity 0.91, sensitivity 0.66, 7.8 probability ratio of a positive test).

Cuantificación de insulinorresistencia con los valores de insulina basal e índice HOMA en una población no diabética / Insulin resistance quantification by fasting insulin plasma values and HOMA index in a non-diabetic population

OBJETIVO: Calcular la prevalencia y definir el síndrome de insulinorresistencia mediante la determinación de insulinemia basal y el índice HOMA, y estudiar su relación con otros componentes del síndrome metabólico. SUJETOS Y MÉTODO: Estudiamos una población de 292 sujetos no diabéticos, de ambos sexos y edades entre 20 y 65 años, seleccionados por un método de muestreo simple aleatorio entre los que consultaron durante un año en un centro de salud (en el área metropolitana de Valencia), mediante un método de búsqueda oportunista. De ellos se seleccionó a un subgrupo formado por 96 sujetos que no tenían características clínicas ni analíticas del síndrome de insulinorresistencia, y se estudiaron los lípidos plasmáticos, parámetros antropométricos, glucosa e insulina plasmática y el valor del índice HOMA. RESULTADOS: El diagnóstico de insulinorresistencia se ha establecido por los cortes del percentil 90 de la subpoblación sin parámetros clínicos ni analíticos del síndrome de insulinorresistencia, considerando una insulina plasmática basal de 16,7 mU/l o superior, o índice HOMA de 3,8 o mayor. El índice HOMA es más sensible que la insulina plasmática para el diagnóstico de insulinorresistencia. La prevalencia de insulinorresistencia (HOMA 3,8) en la población estudiada por nosotros es elevada, 31,8 por ciento, siendo más frecuente en hombres que en mujeres. CONCLUSIONES: Además de los valores plasmáticos de insulina e índice HOMA, los mejores indicadores clinicobioquímicos de insulinorresistencia son los valores de glucemia en ayunas, el índice de masa corporal (IMC) y los triglicéridos plasmáticos. Así, la razón de probabilidad de tener insulinorresistencia es de 5,9, 2,6 y 2,2, respectivamente para glucemia 110 mg/dl, IMC 25 kg/m2 y triglicéridos 150 mg/dl (AU)