[Gaucher's disease. Report of 4 cases]. / Enfermedad de Gaucher. Aportación de 4 casos.

Gaucher's disease is a rare condition caused by a deficiency in the lysosomal enzyme called beta-glucocerebrosidase (GBA). The objective of our work was to analyse the clinical, diagnostic and therapeutic characteristics in a group of four patients with Gaucher's disease type 1. The advantages of the new diagnostic and therapeutic techniques are stressed. In all cases the diagnosis was made by means of cyto-histological examination and enzymatic measurement of the beta-glucocerebrosidase activity. A genetic study and genotype determination was made in the four cases. A questionnaire was administered to patients to evaluate their life quality applying the SF36 questionnaire adapted to the Gaucher's disease. All subjects have received enzymatic replacement therapy with the recombinant enzyme imiglucerase (Cerezyme Corporation) with a satisfactory clinical course. Interestingly, eosinophilia was present in one patient, which disappeared after treatment.

A Mediterranean and a high-carbohydrate diet improve glucose metabolism in healthy young persons.

AIMS/HYPOTHESIS: Insulin resistance usually precedes the diagnosis of Type II (non-insulin-dependent) diabetes mellitus. However, in most patients, the clinical expression of the disease could be prevented by dietary and lifestyle changes. We investigated the effects of a diet enriched in monounsaturated fatty acids (Mediterranean diet) and a low fat, high-carbohydrate diet on in vivo and in vitro glucose metabolism in 59 young subjects (30 men and 29 women). METHODS: We carried out an intervention dietary study with a saturated fat phase and two randomized-crossover dietary periods: a high-carbohydrate diet and a Mediterranean diet for 28 days each. We analysed the plasma lipoproteins fractions, free fatty acids, insulin sensitivity and glucose uptake in isolated monocytes at the end of the three dietary periods. RESULTS: In comparison to the saturated fat diet, the CHO and Mediterranean diets induced a decrease of LDL-cholesterol (p < 0.001) and HDL-cholesterol (p < 0.001). Steady-state plasma glucose decreased (p = 0.023) and basal and insulin-stimulated 2-deoxiglucose uptake in peripheral monocytes increased in both diets (CHO and Mediterranean), (p = 0.007) indicating an improvement in insulin sensitivity. Fasting free fatty acids plasma values were correlated positively with steady state plasma glucose (r = 0.45; p < 0.0001). In addition, there was an inverse correlation between the mean glucose of the steady state plasma glucose period and logarithmic values of basal (r = -0.34; p = 0.003) and insulin stimulated glucose uptake in monocytes (r = -0.32; p = 0.006). CONCLUSION/INTERPRETATION: Isocaloric substitution of carbohydrates and monounsaturated fatty acids for saturated fatty acids improved insulin sensitivity in vivo and in vitro, with an increase in glucose disposal. Both diets are an adequate alternatives for improving glucose metabolism in healthy young men and women.

Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men.

BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.

The apolipoprotein A-IV-360His polymorphism determines the dietary fat clearance in normal subjects.

Apolipoprotein IV (apo A-IV) has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. Several polymorphic sites within the gene locus for apo A-IV have been detected. Previous studies have shown that the A-IV-2 isoform produces a different plasma lipid response after the consumption of diets with different fat and cholesterol content. The present study was designed to evaluate whether the apo A-IV 360His polymorphism could explain, at least in part, the interindividual variability observed during postprandial lipemia. Fifty-one healthy male volunteers (42 homozygous for the apo A-IV 360Gln allele (Gln/Gln) and nine carriers of the A-IV-360His allele), homozygous for the apo E3 allele, were subjected to a vitamin A-fat load test consisting of 1 g of fat/kg body weight and 60000 IU of vitamin A. Blood was drawn at time 0 and every hour for 11 h. Plasma cholesterol (C), triacylglycerol (TG), and C, TG, apo B-100, apo B-48, apo A-IV and retinyl palmitate (RP) were determined in lipoprotein fractions. Data of postprandial lipemia revealed that subjects with the apo A-IV 360His allele had significantly greater postprandial levels in small triacylglycerol rich lipoproteins (TRL)-C (P<0.02), small TRL-TG (P<0.01) and large TRL-TG (P<0.05) than apo A-IV 360Gln/Gln subjects. In conclusion, the modifications observed in postprandial lipoprotein metabolism in subjects with the A-IV 360His allele could be involved in the different low density lipoprotein (LDL)-C responses observed in these subjects following a diet rich in cholesterol and saturated fats.

Actividad coagulante del factor VII (FVIIc) en ancianos con cardiopatía isquémica / Coagulant activity of factor VII (FVIIc) in old people with ischemic heart disease

Fundamento. La actividad coagulante del factor VII (FVIIc) aumenta con la edad y es un factor de riesgo en el sujeto de mediana edad, pero no se sabe su protagonismo en el anciano. El objetivo de este trabajo es evaluar si la FVIIc es un factor de riesgo en dicha población. Pacientes y método: Diseño: casos y controles. Formaron el grupo 'casos' 79 pacientes que cumplieron los siguientes criterios de inclusión: a) edad entre 65 y 85 años, y b) ingreso en el Hospital Valle de los Pedroches de Pozoblanco por infarto de miocardio y/o angina inestable en un período comprendido entre 2 años y 6 meses previos al inicio del estudio. El grupo 'control' lo formaron 81 sujetos, de similar edad, extraídos al azar de las listas del Padrón Municipal, excluyendo aquéllos con cardiopatía coronaria. La FVIIc se midió por métodos convencionales. El plasma problema se diluyó con plasma deficiente en FVIIc y se midieron los tiempos de coagulación tras añadir tromboplastina y calcio. La medición se calibró frente a un plasma 'control' y el resultado se presentó en forma de porcentaje sobre el control. Resultados: No hubo diferencias significativas entre la FVIIc entre casos (118,3 [22,2]) y controles (116,5 [24,4]; p = 0,630) en el grupo total. Al estratificar por edad se observó que, en el grupo de más de 75 años, los casos tenían una FVIIc superior a los controles (124,1 [18,2] frente a 113,3 [23,5]; p < 0,05). Al estratificar por sexos se observaron unos resultados en los varones similares al grupo global. En el análisis bivariable, en sujetos con enfermedad coronaria, la FVIIc se relacionó con el colesterol total, cLDL, apoproteína B, índice de masa corporal, HbA1c y edad. Los factores que se relacionaron con la FVIIc en el análisis multivariable fueron la glucosa basal, el índice de masa corporal y de forma negativa con el cHDL. Conclusiones: La FVIIc está elevada en la enfermedad coronaria del sujeto muy anciano, por lo que puede ser un factor de riesgo coronario significativo en este grupo de edad (AU)

The effect of apolipoprotein B xbaI polymorphism on plasma lipid response to dietary fat.

BACKGROUND AND AIMS: Lipid response to dietary fat and cholesterol is, to a large extent, genetically controlled. Apolipoprotein B (apo B) plays a dominant role in cholesterol homeostasis. Several polymorphic sites within or adjacent to the gene locus for apo B have been detected. The X+ allele of the XbaI restriction fragment polymorphism of the apo B gene has been found to be associated with higher serum cholesterol and/or triglyceride levels. In order to study the influence of this mutation on the plasma lipid response in diets of varying fat content, 72 healthy male subjects were studied, 21 X- X- (X-) and 51 X+ (X+ X- or X+ X+). METHODS AND RESULTS: These subjects followed three consecutive 28-day diet periods: one rich in saturated fats (SAT diet; 38% fat, 20% saturated); a National Cholesterol Education Program type I diet (NCEP-I diet) (28% fats, < 10% saturated); and a third monounsaturated (MUFA diet) (38% fats, 22% monounsaturated). The different genotypes can be observed to have significant effects on total and LDL cholesterol concentrations (P < 0.017). X+ individuals had higher levels of total and LDL cholesterol after the consumption of a SAT diet (P < 0.012; P < 0.006, respectively), NCEP diet (P < 0.060; P < 0.054, respectively) and MUFA diet (P < 0.022; P < 0.042, respectively) in comparison with X- individuals. A significant interaction between genotypes and dietary effects was observed for diet-induced changes in plasma triglycerides (P < 0.032). Significant decreases in the absolute values of triglyceride concentrations (-0.18 mmol L(-1), P < 0.024) were noted in the X- subjects after the high intake of a MUFA diet, while no significant differences were observed in the X+ individuals (0.006 mmol L(-1), P < 0.858). CONCLUSIONS: Our results suggest that the total triglyceride response to diet is influenced by the apo B XbaI polymorphism.

Increased high-density lipoprotein-3 binding to leukocytes following weight loss and improved glycemic control in type 2 diabetic patients.

This study evaluates the effect on high-density lipoprotein (HDL) binding activity in cultured granulocytes before and after metabolic control of non-insulin-dependent diabetes mellitus ([NIDDM] type 2 diabetes) patients. In 20 type 2 diabetic patients, diabetic control was accomplished by administration of oral antidiabetic agents and dietary restrictions. Adequate metabolic control was reflected by a decrease in the fasting glucose, glycosylated hemoglobin (HbA1c), mean insulin, and body mass index (BMI). After control of the diabetes, the mean HDL3 cholesterol was increased from 0.918 +/- 0.05 to 1.008 +/- 0.05 mmol/L (P < .05) and apolipoprotein AI (apo AI) was increased from 103 +/- 5.8 to 115 +/- 5.1 mg/dL (P < .01). The HDL3 maximum specific binding was higher after versus before diabetic control, 77 +/- 6 versus 122 +/- 8 ng/mg cell protein (P < .01). This increase was related to an increase in maximum binding ([Bmax] from 4.97 x 10(-10) to 8.3 x 10(-10) mol/L, P < .001), and no significant changes were observed in the Kd (from 1.47 x 10(-7) v 2.04 x 10(-7) mol/L). These results suggest that the metabolic control of type 2 diabetes increases HDL3 binding activity.

Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men.

BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN: : We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.

[Coagulant activity of factor VII (FVIIc) in the elderly with ischemic heart disease]. / Actividad coagulante del factor VII (FVIIc) en ancianos con cardiopatía isquémica.

BACKGROUND: The coagulant activity of factor VII increases with age and is a risk factor in middle aged subjects. Its role in elderly people is still unknown. The aim of this study was to evaluate whether or not FVIIc is a risk factor in such population. STUDY DESIGN: cases and controls study. The group of cases consisted of 79 subjects fulfilling the following criteria: a) age between 65 and 85 years, and b) admission in the Valle de los Pedroches Hospital of Pozoblanco (Córdoba, Spain) due to a myocardial infarction and/or unstable angina, 2 or 6 months before their enrollment. The control group consisted of 81 subjects of similar age, chosen at random from the municipal registry, and excluding those with coronary heart disease. Factor VIIc was measured by conventional methods. Plasma samples were diluted with deficient plasma in FVIIc, and coagulation times were measured after adding thromboplastin and calcium. The measures were compared with a <> plasma and the results were presented as a percentage. RESULTS: There were no significant differences in the FVIIc between cases (118.3 [SD 22.2]) and controls (116.5 [24.4]; p = 0.630) in the total group. When classified according to their age, it was observed that within the group of more than 75 years old, cases had a higher FVIIc than controls (124.1 [18.2] vs 113.3 [23.5]; p < 0. 05). When the classification was carried out according to sex, male presented similar results than the total group. Bivariable analysis showed, in subjects with coronary diseases, that FVIIc was related to total cholesterol, cLDL, apoprotein B, body mass index, HbA1c, and age. Factors related to FVIIc in the multivariable analysis were basal glucose serum level, body mass index; cHDL was negatively related. CONCLUSIONS: FVIIc is higher in very old subjects with coronary diseases so it may be a significant coronary risk factor in this age group.

[Mediterranean diet improves low density lipoprotein susceptibility to oxidative modifications]. / La dieta mediterránea mejora la resistencia a la oxidación de las lipoproteínas de baja densidad.

UNLABELLED: Most experts, specially from Anglo-Saxon countries, recommend a low fat diet in order to prevent cardiovascular diseases. However, mortality rate by ischemic cardiopathy is low in Mediterranean countries, probably because of the consumption of a Mediterranean diet, with a high level of monounsaturated fats provided by the olive oil. We have conducted this study in order to investigate the possible influence of this kind of diet on the oxidation of LDL in vitro, the key element for the development of atherosclerosis. PATIENTS AND METHODS: 41 healthy male subjects were submitted to three consecutive 4-week diets. The first was a saturated fat-rich diet (SAT diet, 38% fat, 20% saturated). This was followed by a low fat diet (NCEP-I, 28% fat, 10% saturated) and after that a Mediterranean diet (38% fat, 22% monounsaturated fat). Plasma levels of total cholesterol, LDL-c, HDL-c, triglycerides, apolipoproteins A-I and B, -tocopherol, and the in vitro susceptibility to oxidation of LDL particles. Both hypolipidemic diets produced a significant decrease in total cholesterol, LDL-c, and apo-B plasma levels. However, it was only the NCEP-I diet that revealed a decrease in the HDL-c. The shift from a saturated fat-rich diet, or a diet rich in carbohydrates, to a Mediterranean diet increased the resistance of LDL particles to oxidation increasing the lag time period (p < 0.038), and decreasing (p < 0.001) the progression rate of the curve of oxidation of LDL. Our results point out two positive consequences of the consumption of a Mediterranean diet by healthy young males, compared with the low fat diet recommended by most Anglo-Saxon experts. On the one hand, the Mediterranean diet increases HDL-c plasma levels, and on the other hand, it decreases the susceptibility of LDL to oxidation. This is why the Mediterranean diet must be recommended in order to prevent cardiovascular diseases.

[The Mediterranean diet improves the profile of male smokers compared with the diet recommended by the American Cholesterol Program (NCEP-I)]. / La dieta mediterránea mejora el perfil lipídico en los varones fumadores en comparación con la dieta recomendada por el Programa Americano de Colesterol (NCEP-I).

BACKGROUND: A study of the effect of smokers' diets on their atherogenic lipidic profile. SUBJECTS AND METHODS: 41 healthy males (32 non-smokers and 9 smokers) consumed consecutively a diet low in fat and rich in carbohydrates (28% total fat content < 10% saturated fats, and 57% carbohydrates), and a diet rich in monounsaturated fatty acids (38% total fat content with 22% monounsaturated fats). At the end of each dietary period, adhesion was confirmed by quantification of LDL cholesterol esters, plasma lipids and insulin levels. RESULTS: There were no significant differences between the age or the body mass of the groups of smokers or non-smokers. After both diets tobacco was found to have a significant effect on triglyceride levels (p < 0.0007), HDLc (p < 0.007), apo A-I (p < 0.02) and the LDLc/HDLc ratio (p < 0.005), revealing an interaction between diet and both HDLc levels (p < 0.004) and LDLc/HDLc ratios (p < 0.003). With the low fat and high monounsaturated fatty acid content diets smokers presented higher triglyceride levels (both with p < 0.0002) and LDLc/HDLc ratios (p < 0.0002 and p < 0.05, respectively) and lower levels of apo A-I (p < 0.002 and p < 0.004, respectively). However, in smokers the HDLc levels were only reduced after the low fat diet (p < 0.0003) and after the diet with a high monounsaturated fat content there was a rise in HDLc levels (p < 0.02) and a drop in the LDLc/HDLc ratio (p < 0.005) compared to the group of non-smokers. There were no significant differences in the insulin levels between groups. CONCLUSION: The atherogenic lipidic profile of smokers is due to an effect of tobacco on the lipidic metabolism. This atherogenic profile is accentuated with a low fat diet rich in carbohydrates and can be rectified to some degree with a diet with a high monounsaturated fatty acid content.

[The diet rich in monounsaturated fat modifies in a beneficial way carbohydrate metabolism and arterial pressure]. / La dieta rica en grasa monoinsaturada modifica de forma beneficiosa el metabolismo de los hidratos de carbono y la presión arterial.

OBJECTIVE: Two dietary regimens recommended for the reduction of coronary risk, by way of their effects on lipid profile, are the diet low in saturated fat and a diet rich in monounsaturated fats (MUFA). However the effects of these diets on carbohydrate metabolism in healthy subjects are not well known. The objective of this study was to compare the effect of both diets on various parameters of carbohydrate metabolism. METHODS: 41 healthy young males were submitted to 3 consecutive diets, each for a duration of 4 weeks. The first diet was rich in saturated fat (SAT) (38% fat, 20% saturated). The second was rich in carbohydrates following the recommendations of the NCEP-I (National Cholesterol Education Program type I) (28% fat, 47% carbohydrates). The last one was a diet rich in monounsaturated fatty acids (38% fat, 22% MUFA). At the end of each dietary period, blood pressure (BP) and blood levels of glucose, insulin and free fatty acids were determined. 29 subjects were also submitted to an oral glucose tolerance test (OGTT) at the end of each diet. RESULTS: The SAT diet induced the highest levels of insulin after the OGTT. The consumption of the MUFA diet determined the lowest levels of fasting blood glucose (-0.60 mmol/l [13%], p < 0.0002), insulin (-9 microUl/ml [47%], p < 0.0002) and free fatty acids (-0.11 mmol/l [24%], p = 0.006), compared to the NCEP-I diet. Systolic and diastolic blood pressure were higher in the NCEP-I diet than during the other periods (SBP: +6 mmHg compare with SAT [5%], p = 0.0001; and +5 mmHg compare with MUFA [4%], p = 0.0001; DBP: +20 mmHg compare with MUFA [27%], p = 0.0001) and +6 mmHg compared with SAT [8%], p = 0.0001). CONCLUSION: Of the diets most commonly used for the treatment and prevention of arteriosclerosis, a diet rich in monounsaturated fats is the most beneficial for the healthy population from the point of view of carbohydrate metabolism and blood pressure.

Dietary fat clearance is modulated by genetic variation in apolipoprotein A-IV gene locus.

Previous studies have shown that the A-IV-347Ser polymorphism is associated with the variability in low density lipoprotein (LDL)-cholesterol response to dietary therapy. The present study was designed to evaluate the association of this polymorphism with the individual variability observed in postprandial lipemic response. This polymorphism was characterized in 50 healthy male subjects homozygous for the apolipoprotein (apo)E3 allele. All subjects were subjected to a vitamin A-fat load test. Blood was drawn at time 0 and every hour over a period of 11 hours. Cholesterol and triglycerides (TG) in plasma and lipoprotein fractions of CH, TG, and retinyl palmitate (RP) were determined. Data from the postprandial lipemia revealed that subjects with the A-IV-347Ser allele (n = 14) have a lower postprandial response in total TG (P < 0.025), large triglyceride rich lipoproteins (TRL) TG (P < 0.02), and small-TRL TG levels (P < 0.007), and a higher postprandial response in large-TRL apoA-IV (P < 0.006) and apoB-100 (P < 0.041) levels than subjects homozygous for the A-IV-347Thr subjects (n = 36). In conclusion, the modifications observed in postprandial lipoprotein metabolism associated with this polymorphism within the apoA-IV gene locus may be involved in the variability in LDL-CH response observed in subjects consuming high saturated fat diets.

[Influence of genetic variation at apoprotein A-1 gene promoter region on plasma lipid levels in heart transplantation patients]. / Influencia de la variación genética en la región promotora del gen de la apoproteína A-I sobre las concentraciones de lípidos en pacientes con transplante de corazón.

BACKGROUND: To study if the presence of the G/A polymorphism at the apo A-I gene promoter region could determine the lipid profile in patients with hyperlipidemia after heart transplantation, or if it is related with the type of heart disease that determined the transplantation. PATIENTS AND METHODS: This study included 31 patients with hyperlipidemia after heart transplantation. Anthropometric parameters, basic analytic and lipid study were measured in these subjects. Identification of the G/A mutation in the promoter region of the apo A-I gene was performed. RESULTS: 22 patients had the G/G genotype and 9 the G/A. 14 were transplanted by coronary heart disease and 17 by non ischemic heart disease. Patients with the A allele had higher cHDL (63 [SD 15] vs 53 [10]; p = 0.034) and apo A-I plasma levels (156 [34] vs 132 [24]; p = 0.040) than G/G subjects. The A allele was present in the 18% of the patients transplanted by ischemic heart disease and in the 43% of the transplanted by another etiology (p = 0.073). CONCLUSIONS: The presence of the G/A genotype in the promoter region of the apo A-I gene determines higher plasma levels of cHDL in patients with hyperlipidemia after heart transplantation.

The SstI polymorphism of the apolipoprotein C-III gene determines the insulin response to an oral-glucose-tolerance test after consumption of a diet rich in saturated fats.

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevated triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are characteristic of an insulin-resistant state. To study the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was rich in saturated fat [15% protein, 47% carbohydrate, 38% fat (20% saturated)], the second was a National Cholesterol Education Program Step 1 diet [15% protein, 57% carbohydrate, 28% fat (< 10% saturated)], and the last was rich in monounsaturated fat [15% protein, 47% carbohydrate, 38% fat (22% monounsaturated, < 10% saturated)]. At the end of each dietary period, subjects received an oral-glucose-tolerance test (OGTT). Apo C-III genotype significantly affected basal glucose concentrations (P < 0.045) and insulin concentrations after the OGTT (P < 0.012). APOC3*S1/APOC3*S2 subjects (n = 13) had higher insulin concentrations after the OGTT than APOC3*S1/APOC3*S1 subjects (n = 28) in the 3 periods (diet 1: P < 0.0004; diet 2: P < 0.01; diet 3: P < 0.008). Multiple regression analysis showed that this polymorphism predicted the insulin response to the OGTT (P < 0.031) and the difference between basal insulin concentrations and insulin concentrations after the OGTT (P < 0.002) with the saturated fat diet. In summary, our results suggest that the mutation in the apo C-III gene affects insulin response to an OGTT, which could result in reduced sensitivity to insulin, especially when persons consume diets rich in saturated fat.

Plasma lipid response to hypolipidemic diets in young healthy non-obese men varies with body mass index.

Lipid response to dietary fat is highly variable among individuals of a population. The aim of this study was to establish whether being overweight is one of the factors that determines this response. Forty-one non-obese healthy men were divided into two groups according to body mass index as follows: controls, <25 kg/m2; overweight, >25 kg/m2 but <30 kg/m2. After consuming a saturated fat-rich diet (SAT diet: 38% fat, 20% saturated) for 4 wk, subjects were switched to a low fat diet [National Cholesterol Education Program (NCEP)-I diet: 28% fat, 10% saturated] for 4 wk and then to a monounsaturated fat-rich diet (MUFA diet: 38% fat, 22% monounsaturated) for 4 wk. Data were analyzed by Student's t test and two-way ANOVA for repeated measures. After consuming the NCEP-I diet, the overweight subjects had a smaller decrease relative to the SAT diet period in plasma total cholesterol [-0.30 vs. -0.67 mmol/L (-7 vs. -16%), P < 0.02] and low density lipoprotein-cholesterol concentrations [-0.24 vs. -0.55 mmol/L (-9 vs. -21%), P < 0.04] than controls. However, in the overweight subjects, the MUFA diet produced a greater decrease in plasma triglycerides than in the controls relative to the SAT diet period [-0.36 vs. -0.03 mmol/L (-26 vs. -4%), P < 0.006] and to the NCEP-I diet period [-0.29 vs. 0. 01 mmol/L (-22 vs. 1%), P < 0.01). Plasma cholesterol concentrations changed to a lesser extent, and triglyceride concentration to a greater extent, in overweight but non-obese young men than in those of normal weight in response to changes in dietary fat composition. Our data suggest that in the diet treatment of obese hyperlipemic subjects, it is more important for them to lose weight than to change the fat composition of their diets.

Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlidemia.

BACKGROUND: Oxidized low-density lipoprotein plays an important role in the development of atherosclerosis. We evaluated the effect of two lipid-lowering drugs, bezafibrate and lovastatin, on the susceptibility of low-density lipoproteins for oxidation in vitro in 21 heart transplant recipients with hyperlipidemia. METHODS: Patients were given the same diet for 3 months, and after that they were randomized to lovastatin or bezafibrate for a period of 8 weeks and then crossed over to an additional 8 weeks of either bezafibrate or lovastatin. Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment. RESULTS: The low-density lipoproteins of transplant recipients presents a shorter lag time than in control subjects (64+/-3 vs 80+/-4 minutes, respectively). This parameter increases after both bezafibrate and lovastatin treatment (83+/-5 and 80+/-4 minutes, respectively). Moreover, we did observe a negative correlation between insulinemia and the lag time of oxidation after bezafibrate treatment (r = -0.5014, P < .021) and between the polyunsaturated fatty acids/monounsaturated fatty acids ratio in low-density lipoprotein cholesterol esters and lag time after lovastatin treatment (r = -0.4631, P < .04). CONCLUSIONS: Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlipemia.

Dietary fat clearance in normal subjects is modulated by genetic variation at the apolipoprotein B gene locus.

Apolipoprotein B (apo B) plays a dominant role in cholesterol homeostasis. Several polymorphic sites within or adjacent to the gene locus for apo B have been detected. The X+ allele (XbaI restriction site present) of the XbaI restriction fragment polymorphism on the apo B gene has been found in some studies to be associated with higher serum cholesterol and/or triglyceride levels and with greater dietary response. The present study was designed to evaluate whether the apo B XbaI polymorphism was associated with the interindividual variability observed during postprandial lipemia. Fifty-one healthy young male volunteers [20 X-/X- (X-), and 31 X+/X- or X+/X+ (X+)], homozygotes for the apo E3 allele, were subjected to a vitamin A-fat load test. Subjects with the X- genotype had significantly greater retinyl palmitate (RP) and apo B-48 postprandial responses on both the large and the small TRL lipoprotein fractions compared with X+ subjects. In summary, subjects with the X-/X- genotype at the apo B locus have a greater postprandial response than X+ subjects. These differences observed in postprandial lipoprotein metabolism could explain some of the reported associations of this polymorphism to coronary heart disease risk.