Contribution of polymorphisms in the apolipoprotein AI-CIII-AIV cluster to hyperlipidaemia in patients with gout.

BACKGROUND: Studies have shown that hyperuricaemia is independently related to the insulin resistance syndrome and that polymorphisms of the apolipoprotein AI-CIII-AIV cluster are also related to insulin resistance. OBJECTIVE: To study the prevalence of polymorphisms of the apolipoprotein AI-CIII-AIV cluster in persons with gout and to determine whether these polymorphisms contribute to the pathophysiology of gout or to altered lipid concentrations. METHODS: Plasma cholesterol, triglycerides, uric acid, VLDL, LDL, IDL, and HDL triglycerides, cholesterol, and the renal excretion of uric acid were measured in 68 patients with gout with gout and 165 healthy subjects. Polymorphisms were studied by amplification and RFLP in all subjects, using XmnI and MspI in the apolipoprotein AI gene and SstI in the apolipoprotein CIII gene. RESULTS: The A allele at position -75 bp in the apolipoprotein AI gene was more common in patients with gout than in controls (p = 0.01). Levels of cholesterol, triglycerides, uric acid, basal glycaemia, and HDL cholesterol were higher in the patients (p<0.001). In the patients there was also an interaction between mutations at the two polymorphic loci studied in the apolipoprotein AI gene (p = 0.04). An absence of the mutation at position -75 bp of the apolipoprotein AI gene resulted in increased plasma triglyceride levels. CONCLUSIONS: Gouty patients have an altered allelic distribution in the apolipoprotein AI-CIII-AIV cluster, which could lead to changes in levels of lipoproteins. This is not caused by a single mutation but rather by a combination of different mutations.

Association of biological markers of activity of systemic lupus erythematosus with levels of anti-oxidized low-density lipoprotein antibodies.

OBJECTIVES: To study the levels of anti-oxidized low-density lipoprotein (LDL) antibodies in patients with systemic lupus erythematosus (SLE) at two different points during the disease, and evaluate their relation with markers of SLE activity in serial blood samples. To investigate the correlations at two points in time between anti-oxidized LDL antibodies and anti-beta2-glycoprotein-I antibodies, leucocytes, immunoglobulin G, anti-deoxyribonucleic acid, complement 3, complement 4 and the disease activity index. METHODS: A total of 49 patients with SLE according to ACR criteria were studied at two points, 3 to 4 months apart, Time 1 and Time 2. RESULTS: There were ostensible changes in levels of anti-oxidized LDL antibodies between Times 1 and 2, which correlated significantly with disease activity markers. The association between levels of anti-oxidized LDL antibodies and complement system activation remained after multiple regression analysis with stepwise adjustment. CONCLUSIONS: Antibody levels against oxidized LDL vary with time and are closely related to the degree of SLE activity. There is an association between levels of autoantibodies to oxidized LDL and complement system activation.

The elevated prevalence of apolipoprotein E2 in patients with gout is associated with reduced renal excretion of urates.

OBJECTIVE: Previous studies have demonstrated that the lower renal excretion of urates in patients with hyperuricaemia is inversely related to plasma very low-density lipoprotein (VLDL) levels, and the different genotypes of the apolipoprotein E gene are related to the plasma levels of lipids. The aim of this study was to determine the prevalence of apolipoprotein E in hyperuricaemic patients and to investigate whether the renal excretion of urates is conditioned by the apoliprotein E genotype. METHOD: The plasma levels of lipoproteins, cholesterol, triglycerides and uric acid, and the renal excretion of uric acid were studied in 68 patients with gout and in another control group of 50 healthy subjects. Both groups were genotyped for apolipoprotein E by means of an amplification technique and inverse hybridization. RESULTS: The prevalence of the E2 allele was greater in the patients than in the control group. The levels of cholesterol, triglycerides and uric acid were greater in the patients, whereas the levels of high-density lipoprotein were lower. The patients with the E2 allele had higher levels of triglycerides in VLDL and intermediate-density lipoproteins and a lower renal excretion of urates. CONCLUSIONS: These results show that the reduced renal excretion of uric acid in patients with gout is mediated by high levels of VLDL and by the high prevalence of the E2 allele of apolipoprotein E.

Dietary fatty acids modify insulin secretion of rat pancreatic islet cells in vitro.

The type of dietary fat affects the action of insulin by changes induced in the fatty acid composition of cell membranes. Little is known, however, about the effects of dietary fatty acids on insulin secretion or the possible relation between the fatty acid composition of the membrane phospholipids and insulin secretion. We therefore studied the effects of dietary fatty acids on insulin secretion stimulated by glucose, forskolin and arginine, and on the insulin content of isolated pancreatic islets, as well as on the fatty acid composition of muscle phospholipids, which were used as markers of the diet-induced modifications in the cell membranes. Five groups of rats were fed for one month with diets varying only in their fat composition: olive oil, sunflower oil, soybean oil, fish oil and palmitic acid (16:0) + soybean oil (SAT). The SAT group had higher insulin secretion, independently of the secretagogue used. No significant differences were found in insulin content between the groups. The dietary fatty acids modified the fatty acid composition of the muscle phospholipids, both in endogenously synthesized fatty acids and in those which were unable to be synthesized by the organism. No statistically significant relation was found between insulin secretion and the content of certain fatty acids in the muscle phospholipids.

Increased levels of anti-oxidized low-density lipoprotein antibodies are associated with reduced levels of cholesterol in the general population.

Autoantibodies against epitopes of oxidized low-density lipoprotein (LDL), initially shown in human sera, were later related with the atherosclerotic process, although recent studies have questioned this association. Moreover, their association with total cholesterol and plasma LDL, or with the other lipoproteins, is not clear. We studied the relation between the levels of autoantibodies to oxidized LDL and lipoproteins in a population of 400 subjects from the lower Guadalhorce area in Malaga, Spain. Anti-oxidized LDL antibodies were measured by enzyme-linked immunosorbent assay (ELISA), and total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and lipoprotein(a) [Lp(a)] were measured with commercial kits. Subjects who were positive for anti-oxidized LDL antibodies had significantly lower levels of total cholesterol (P <.01) and LDL cholesterol (P <.01). There was a negative correlation between titers of anti-oxidized LDL antibodies and levels of total cholesterol (P =.007) and LDL cholesterol (P =.024). This inverse relation between the levels of anti-oxidized LDL antibodies and the levels of total cholesterol and LDL cholesterol in a large population study, together with the discordances already published, suggests that the relation between anti-oxidized LDL antibodies, arteriosclerosis, and lipids is more complex than initially thought.

Varying incorporation of fatty acids into phospholipids from muscle, adipose and pancreatic exocrine tissues and thymocytes in adult rats fed with diets rich in different fatty acids.

Despite numerous studies, the importance which the tissue or the composition of the diet may have in the biological distribution of each fatty acid is not well known. To determine the importance of tissue origin and dietary fatty acids in the fatty acid composition of cell phospholipids, 54 male adult rats were fed isocaloric diets for one month varying only in their fatty acid compositions. The fat component of the six experimental groups was derived from olive oil, sunflower oil, fish oil, soybean oil, palmitic acid, or 82% palmitic acid plus 18% soybean oil, supplying the essential fatty acid. The fatty acid composition of phospholipids from thymocytes, pancreatic exocrine, muscle and adipose tissues was studied by gas-chromatography. The tissue of origin was a more important source of variation than diet in the fatty acid content of the cell phospholipids except for palmitic acid (16:0), eicosapentaenoic acid (20:5 n-3), and docosahexaenoic acid (22:6 n-3). This study points out the complexity of the interrelations between different families of fatty acids and of the specificity of each tissue to changes in the composition of dietary fatty acids, as well as the inconvenience of speaking from the dietary point of view of groups of fatty acid families based on the position of the double bond, since their individual behaviour, including saturated fatty acids, is very different in the face of dietary manipulation. The study also highlights the different behaviour of each of the fatty acids in relation to the others in the diet in each of the tissues, a circumstance which should be taken into account when evaluating the biological effects in both epidemiological and experimental studies.

Serum leptin and habitual fatty acid dietary intake in patients with type 1 diabetes mellitus.

OBJECTIVE: To study the contribution of a normal intake of nutrients to the variability of serum leptin concentrations in persons with type 1 diabetes mellitus. DESIGN: We studied the relation between serum leptin and nutrient intake in a cross-sectional study. METHODS: Serum leptin measured by radioimmunoassay, nutritional data determined by a self-administered 7-day nutritional questionnaire, and the fatty acid composition of the serum phospholipids (measured by thin layer chromatography and gas chromatography) were determined in 60 patients with type 1 diabetes mellitus. Correlation and regression analyses were performed between serum leptin and dietary fatty acids and serum phospholipid fatty acids. RESULTS: In the prediction models for the concentrations of serum leptin in men with type 1 diabetes mellitus, the dietary fatty acids displaced the anthropometric variables, and were independent of the serum testosterone concentrations. This fact remained when the prediction was made on the basis of indirect markers of the intake, such as the serum phospholipid fatty acids. In the women, the fatty acids from the diet or from the serum phospholipids also partly explained the variation in serum leptin, although not displacing the anthropometric variables. CONCLUSIONS: Our data suggest that, in non-experimental conditions, the concentrations of serum leptin in men with type 1 diabetes mellitus and, to a lesser extent, those in women with diabetes, may be influenced by the composition of the habitual diet, especially the type of dietary fat.

Lipoproteins in patients with isolated hyperuricemia.

BACKGROUND: There have been described abnormalities in the lipoprotein profile of hyperuricemic patients, it has not been clarified wether these abnormalities are due to the hyperuricemia or to the dyslipema often associated to these patients. Our aim is to study the apolipoprotein profile in hyperuricemic patients without dyslipemia compared to a control population. PATIENTS AND METHODS: 30 hyperuricemic patients and 26 healthy controls. Measurements were of blood uric acid, total cholesterol, total triglycerides, creatinine, HDL-C, and VLDL cholesterol, triglyceride, Apo B, Apo CII and Apo CIII (1 and 2). Uric acid clearance and fractionated excretion were measured in 24 h. urine samples. RESULTS: No significant differences were found between hyperuricemic and control patients in cholesterol, triglycerides and apo B in VLDL, or LDL and HDL cholesterol. The levels of apo B, Apo AI levels and apo CIII/apo CII were similar in the hyperuricaemic and controls. CONCLUSIONS: There are two types of hyperuricaemic patients, one group associated to hyperlipideamia and would be included in the X Syndrome. The other group not associated to other metabolic abnormalities. Is important to distinguish between these two groups to define the prognosis of a given patient because the greater cardiovascular risk linked hyperuricaemic patients could be related to the association to others cardiovascular risks factors.

Dietary alterations in plasma very low density lipoprotein levels modify renal excretion of urates in hyperuricemic-hypertriglyceridemic patients.

Hyperuricemic-hyperlipidemic patients exhibit decreased renal excretion of urates relative to purely hyperuricemic patients; also, very low density lipoprotein (VLDL) levels are inversely proportional to the amount of urate excreted. Based on this knowledge, the aim of this study was to alter VLDL levels by dietary manipulation and assess its effect on uric acid levels and renal excretion of uric acid. Thirty-six men were studied in 2 groups consisting of 20 primary hyperuricemic (group I) and 16 primary hyperuricemic-hypertriglyceridemic patients (group II). The patients were analyzed for apoproteins and lipoproteins, urate levels, and renal excretion of uric acid in a first, basal determination, after 3 weeks of a 1200-Cal diet, and after another 3 weeks of a 2500-Cal diet. After the 1200-Cal diet, patients in group I exhibited significantly decreased levels of cholesterol (P < 0.05) and apoprotein CIII (P < 0.05). There were significant differences in renal excretion of uric acid (P < 0.05) between the basal and third determinations. Patients in group II exhibited significantly decreased levels of triglycerides (P < 0.01), VLDL cholesterol (P < 0.01), VLDL triglycerides (P < 0.01), and VLDL apoprotein B (P < 0.05) after the 1200-Cal diet; all of these parameters returned to values similar to the basal levels on completion of the 2500-Cal diet. With regard to purine parameters, the low calorie diet led to significantly increased fractional excretion of uric acid (P < 0.01) and uric acid clearance (P < 0.01), both of which decreased significantly to values near basal after the 2500-Cal diet. The results obtained in this study reveal that the decreased levels of triglyceride and VLDL components that arise from a low calorie diet are accompanied by increased renal excretion of urates and that the increase in the amount of this type of lipoprotein particle with an increase in dietary energy offsets the increase in renal excretion of urate.

Unsaturated fatty acids alter the insulin secretion response of the islets of Langerhans in vitro.

The aim of the present study is to examine the influence which different concentrations of free fatty acids (FFAs) have on the insulin secretion response of the islets of Langerhans when the culture is prolonged over a week. Animals were killed by decapitation and pancreatic islets of Langerhans isolated. The islets were incubated in enriched RPMI and oleic or linoleic acid was added at concentrations of 0.04, 0.1, 0.375, and 1 mmol/l. The medium without FFAs was used as a control. The culture time was 7 days. For insulin secretion studies, islets were selected after preincubation in batches of six islets in 1 ml of KRB (Krebs-Ringer buffer) containing one of the following: 5.5, 11.1, 16 or 26.7 mmol/l glucose, 10 mumol/l forskolin or 20 mmol/l arginine. The results showed a significant increase in insulin secretion observed after culture with 1 mmol/l oleic and linoleic acid compared to the other concentrations and the control culture for all the secretagogues used. However, at this same concentrations no increase was observed in insulin secretion as the glucose concentration rose, and this was noticeable with linoleic acid at concentrations of 0.375 mmol/l. In conclusion, culture of islets of Langerhans for a week with high concentrations of unsaturated fatty acids produces a hypersecretion of insulin which is not influenced by secretagogues such as glucose, arginine, or forskolin. The loss of gluco-sensitivity may become greater as the degree of unsaturation of the fatty acid used increases.

[Lipoprotein profile in patients with isolated hyperuricemia]. / Perfil lipoproteico en pacientes con hiperuricemia aislada.

There have been described abnormalities in the lipoprotein profile of hyperuricemic patients, it has not been clarified wether these abnormalities are due to the hyperuricemia or to the hyperlipidemia often associated to these patients. Our aim is to study the apolipoprotein profile in hyperuricemic patients without hyperlipidemia compared to a control population. 30 hyperuricemic patients and 26 healthy controls. Measurements were of blood uric acid, total cholesterol, total triglycerides, creatinine, HDL-C, and VLDL cholesterol, triglyceride, Apo B, Apo CII and Apo CIII (1 and 2). Uric acid clearance and fractionated excretion were measured in 24 h. urine samples. No significant differences were found between hyperuricemic and control patients in cholesterol, triglycerides and apo B in VLDL, or LDL and HDL cholesterol. The levels of apo B, Apo AI levels and apo CIII/apo CII were similar in the hyperuricemic and controls. There are two types of hyperuricemic patients, one group associated to hyperlipidemia and would be included in the X Syndrome. The other group not associated to other metabolic abnormalities. Is important to distinguish between these two groups to define the prognosis of a given patient because the greater cardiovascular risk linked hyperuricemic patients could be related to the association to others cardiovascular risks factors.

Increased VLDL levels and diminished renal excretion of uric acid in hyperuricaemic-hypertriglyceridaemic patients.

The objective was to study the lipoprotein levels in primary hyperuricaemic patients and to analyse their renal management or urates in order to check for some potential influence of altered lipid levels on the renal excretion of urates by this type of patient. Overall 115 male individuals were studied in five groups, namely: 30 primary hyperuricaemic (group I); 27 primary hyperuricaemic-hypercholesterolaemic (group II); nine primary hyperuricaemic-hypertriglyceridaemic (group III); 33 primary hyperuricaemic-mixed hyperlipidaemic (group IV); and 16 normouricaemic-normolipidaemic subjects (group C). All patients were subjected to blood analyses for uric acid, total triglycerides, total protein, creatinine, high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, low density lipoprotein (LDL) cholesterol, apoprotein (apo) AI, apoprotein B, apoprotein CII and apoproteins CIII1 and CIII2. For urine analysis creatinine, creatinine clearance, uric acid excretion, clearance and fractional excretion were measured in 24 h urine samples. Mixed and pure hyperuricaemic-hypertriglyceridaemic patients exhibited increased levels of VLDL components, decreased fractional excretion of uric acid and increased apo CIII/CII ratios. The increased levels of structural VLDL components were negatively (and statistically significantly) correlated with the fractional excretion of uric acid; this suggests a close biological relationship between the two parameters. Taking into account the role played by apo C in VLDL metabolism, the altered apo CIII/CII ratios found in hyperuricaemic-hypertriglyceridaemic patients (both pure and mixed) suggest that this apoprotein plays a central role in the physiopathology of the alterations observed.

Does the intake of nuts and seeds alter the appearance of menarche?

BACKGROUND: The nutritional state reportedly influences the age of menarche. In this work we investigated the potential relationship between the intake of various types of foods and the age of menarche, irrespective of body weight. METHODS: An overall 777 schoolgirls of ages between 8 and 16 years from Benalmádena (Málaga, Spain) were subjected to a cross-sectional study involving: the age of menarche as the dependent variable; and the weight, body mass index, skinfold thickness, food intake (estimated from weekly food frequency questionnaires), and age of menarche in the proband's mother and sisters as independent variables. Several models were developed in order to calculate the strength of association between the dependent variable (the presence or absence of menarche) and the independent variables. RESULTS: The average age of menarche was 12.4 years. The intake of the various types of foods was not consistent between the different age groups. In girls of 12 or younger, the age of menarche was found to be related to weight: Odds ratio (OR) = 7.06; (Confidence intervals (CI) = 2.80-17.6). On inclusion of various foods groups, the OR rose to 49.89 (CI = 40.85-60.84). In girls over 12, the age of menarche was essentially related to the intake of nuts and seeds (OR = 0.71, CI = 0.40-0.98). Inclusion of other foods groups decreased the OR (OR = 0.34, CI = 0.14-0.39). CONCLUSIONS: Significant statistical relationship between intake of nuts and seeds and the age of menarche was found.