Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome--LIPGENE: a European randomized dietary intervention study.

BACKGROUND: Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS. OBJECTIVE: This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS. DESIGN: A free-living, single-blinded dietary intervention study. SUBJECTS AND METHODS: MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined. RESULTS: In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P < 0.01), particularly in men. CONCLUSION: There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

Basal plasma concentrations of plant sterols can predict LDL-C response to sitosterol in patients with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with a high risk of coronary heart disease. Pharmacological treatment and diet are both essential for the management of FH. Foods rich in plant sterols (PS) may play an important role in the treatment of patients with these disorders. OBJECTIVE: To test the effect of the intake of PS on low-density lipoprotein (LDL) concentration, endothelial function (EF) and LDL particle size in 30 patients with FH. DESIGN: Randomized and crossover dietary intervention study. SETTING: Tertiary outpatient care. SUBJECTS: Thirty-eight were recruited, but only 30 were subjected to four low-fat dietary intervention periods, each of 4 weeks. METHODS: Each intervention had a different content of cholesterol (<150 or 300 mg/day) and sitosterol (<1 or 2 g/day). Lipid response, EF and LDL particle size were analysed after the intervention. RESULTS: Plasma sitosterol/cholesterol ratio was higher during both plant sterol-rich periods than during the low plant sterols periods. Basal sitosterol concentrations predicted the LDL-cholesterol response during the intake of plant sterol-enriched diets. The change in LDL-cholesterol was significantly greater in subjects in the upper and intermediate tertiles of basal plasma sitosterol concentrations (-21+/-8 mg/dl, P=0.03; -19+/-7 mg/dl, P=0.04, respectively) than in subjects in the lower tertile (8+/-5 mg/dl) when they changed from a low cholesterol diet to a low cholesterol plus plant sterol diet. CONCLUSION: Our study demonstrates that basal sitosterol values can predict hypolipidemic response in patients with FH.

Cerivastatin improves insulin sensitivity and insulin secretion in early-state obese type 2 diabetes.

In a double-blind, placebo-controlled, randomized crossover study, 15 stable mild hyperglycemic patients without treatment and with features of metabolic syndrome were treated with cerivastatin (0.4 mg/day) or placebo for 3 months. The insulin sensitivity index during the euglycemic-hyperinsulinemic clamp (EHC; 5.4 mmol/l; 80 mU x m(-2) x min(-1)) was increased by cerivastatin treatment (66.39 +/- 3.9 nmol x lean body mass [LBM](-1) x min(-1) x pmol(-1) x l(-1)) as compared with placebo (58.37 +/- 3.69 nmol x LBM(-1) x min(-1) x pmol(-1) x l(- 1); P < 0.01) by 13.7%. Glucose oxidation during EHC was significantly higher with statin treatment (16.1 +/- 1.37 micromol x LBM(-1) x min(-1)) as compared with placebo (14.58 +/- 1.48 micromol x LBM(-1) x min(-1); P < 0.05). During hyperinsulinemia (approximately 800 pmol/l) in EHC steady-state, lipid oxidation was significantly decreased and respiratory quotient was significantly increased with statin treatment (0.33 +/- 0.05 mg x LBM(-1) x min(- 1), 0.94 +/- 0.01) as compared with placebo (0.48 +/- 0.06 mg x LBM(-1) x min(-1), 0.91 +/- 0.01; P < 0.01 and P < 0.05, respectively). During statin treatment, the first-phase insulin response increased from 2.07 +/- 0.28 to 2.82 +/- 0.38 pmol x l(-1) x pmol(-1) (P < 0.05). The second phase of insulin responses examined by C-peptide and insulin levels averaged during the hyperglycemic clamp (20 mmol/l) was unchanged. In conclusion, this study demonstrates that 0.4 mg cerivastatin therapy improves first-phase insulin secretion and increases insulin-mediated glucose uptake and respiratory quotient in the early state of obese type 2 diabetes.

A carbohydrate-rich diet reduces LDL size in QQ homozygotes for the Gln 192Arg polymorphism of the paraoxonase 1 gene.

Paraoxonase 1 (PON 1) is an esterase with antioxidant properties that is present in HDL. Gln192Arg polymorphism (also named Q192R or Q/R) of the PON 1 gene that encodes this protein defines two alleles (Q and R). The R allele has been associated with higher cardiovascular risk. LDL size and susceptibility to oxidation also have been identified as cardiovascular risk factors. Our objective was to determine whether genetic variations in the Gln192Arg polymorphism influence LDL size and susceptibility to oxidation after the consumption of diets with different fat content. In our experiments, the participants (n = 98) underwent three 4-wk diets--one, saturated fat-enriched (SAT); another, monounsaturated fat-enriched (MONO); and a third, carbohydrate-enriched (CHO). We observed that LDL were smaller in the QQ group after the CHO diet vs. the SAT (P < 0.01) and MONO diets (P < 0.03). No differences in LDL size were found in QR/RR subjects. When we analyzed lag time of oxidation of LDL, we found that when carriers of the R allele (QR/RR) received the MONO diet, the lag period of LDL oxidation was longer as compared with the CHO diet. Otherwise, we found no differences in QQ homozygotes when we evaluated the lag time of oxidation of LDL after the three diets. These results suggest that the Glnl92Arg polymorphism of the paraoxonase gene influences LDL size and susceptibility to oxidation in response to diet.

Postprandial lipemia is modified by the presence of the polymorphism present in the exon 1 variant at the SR-BI gene locus.

It has recently been reported that carriers of the less common allele at the scavenger receptor class B type I (SR-BI) exon 1 polymorphism are more susceptible to the presence of saturated fatty acid in the diet because of a greater increase in LDL cholesterol. Our aim was to determine if this polymorphism could also influence postprandial lipoprotein metabolism, because the SR-BI has been described as a possible mediator in the intestinal absorption of triacylglycerols. Forty-seven normolipidemic volunteers who were homozygous for the E3 allele at the APOE gene were selected [37 homozygous for the common genotype (1/1) at the SR-BI exon 1 polymorphism and 10 heterozygous (1/2)]. They were given a fat-rich meal containing 1 g fat and 7 mg cholesterol per kg body weight and vitamin A 60,000 IU/m2 body surface. Fat accounted for 60% of calories, and protein and carbohydrates accounted for 15% and 25% of energy respectively. Blood samples were taken at time 0, every 1 h until 6 h, and every 2.5 h until 11 h. Total cholesterol and triacylglycerols in plasma, and cholesterol, triacylglycerols and retinyl palmitate in triacylglycerol-rich lipoproteins (large and small triacylglycerol-rich lipoproteins) were determined. Postprandial responses for triacylglycerols and retinyl palmitate in small triacylglycerol-rich lipoproteins were higher in 1/1 individuals than in 1/2 individuals. No other significant differences were noted. Our data show that the presence of the genotype 1/2 is associated with a lower postprandial lipemic response.

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.

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.

Effect of phorbol ester TPA on macrophage metabolic activity.

Metabolically active macrophages are known to play a role in tumor immune surveillance, not only as effector cells but also as collaborators in T cell mediated immune response. The present work reports that non-toxic concentrations of the tumor promoter TPA, stimulate the adherence of murine peritoneal macrophages after short time incubation, while TPA pretreatment for periods longer than 4 hrs suppresses phagocytosis, RNA and protein synthesis by these cells. Although inhibition of macrophage metabolic activity could play an additional role in tumor promotion, the enhancing and depressing effects of TPA on the immune system must be weighed before it can be assumed that TPA acts in vivo primarily to depress the immune system.

[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.

Central obesity and altered peripheral adipose tissue gene expression characterize the NAFLD patient with insulin resistance: Role of nutrition and insulin challenge.

OBJECTIVE: Insulin resistance (IR) and white adipose tissue (WAT) dysfunction frequently are associated with nonalcoholic fatty liver disease (NAFLD); however, the pathogenic mechanisms contributing to their clustering are not well defined. The aim of this study was to define some nutritional, anthropometric, metabolic, and genetic mechanisms contributing to their clustering. METHODS: Forty-five (20 men, 25 women) patients (age 45.7 ± 11.1 y) with recent diagnosis of NAFLD were grouped according to IR state. Energy balance was assessed using a food questionnaire and indirect calorimetry, and body composition with anthropometry and dual-energy x-ray absorptiometry. Biochemical and hormonal parameters combined with adipose tissue gene expression were determined. Microarray analysis of gene expression was performed in a subset of WAT samples from IR patients (n = 9), in the fasted state, after specific test meals (monounsaturated fatty acid [MUFA], saturated fat [SAT], and carbohydrate-rich) and after being challenged with insulin. RESULTS: IR patients exhibited higher trunk fat to leg fat ratio (P < 0.05) and had a higher ratio of SAT/MUFA fat intake (P < 0.05) than insulin-sensitive (IS) individuals. Deposition of fat in the trunk but not in the leg was directly related to liver enzyme levels (P < 0.05). IR patients also had lower adiponectin serum levels and leptin (LEP) mRNA expression in WAT compared with IS patients (P < 0.01 and P < 0.05, respectively). Microarray analysis after insulin challenge confirmed that insulin treatment induces the expression of PPARG gene and LEP and decreases GCGR gene (P < 0.05 for all) in WAT. No changes in these genes were observed in the postprandial state induced after the acute effect of specific diets. CONCLUSIONS: Patients exhibiting NAFLD and IR had preferential central fat deposition directly related to their serum alanine aminotransferase levels. These patients showed peripheral adipose tissue dysfunction and exhibited inappropriately low LEP biosynthesis that could be partially restored after anabolic conditions induced by insulin signaling.

A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome.

OBJECTIVE: Dietary changes are major factor in determining cardiovascular risk. We assessed the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (MetS) from the LIPGENE project. METHODS AND DESIGN: Clinical intervention study: the patients (n=337) were randomly assigned to one of four diets for 12 weeks each: two high fat diets, one rich in saturated fat (HSFA) and the other rich in monounsaturated fat (HMUFA), and two low fat diets, one high in complex carbohydrates (LFHCC) supplemented with 1.24g/day of long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) and the other LFHCC diet with placebo (LFHCC). MEASUREMENTS: the effects on MetS risk criteria were recorded before and after the intervention period. RESULTS: An enlarged waist circumference (≥88cm for women and ≥102cm for men) was present among 95% of the participants, 88% had elevated blood pressure (>130/85mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (≥5.55mmol/L), 51% were hypertriacylglycerolemic (≥1.7mmol/L), and 72% had low HDL cholesterol (<1.0mmol/L for men, and <1.3mmol/L for women). The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (p<0.05). Thus the prevalence of MetS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (p<0.028). CONCLUSIONS: The consumption of a low-fat high-carbohydrate supplemented with n-3 diet reduced the risk of MetS as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets.

Monounsaturated fat-rich diet prevents central body fat distribution and decreases postprandial adiponectin expression induced by a carbohydrate-rich diet in insulin-resistant subjects.

OBJECTIVE: Central obesity is associated with insulin resistance through factors that are not fully understood. We studied the effects of three different isocaloric diets on body fat distribution, insulin sensitivity, and peripheral adiponectin gene expression. RESEARCH DESIGN AND METHODS: Eleven volunteers, offspring of obese type 2 diabetic patients with abdominal fat deposition, were studied. These subjects were considered insulin resistant as indicated by Matsuda index values <4 after an oral glucose tolerance test, and they maintained A1C <6.5% without therapeutic intervention. All subjects underwent three dietary periods of 28 days each in a crossover design: 1) diet enriched in saturated fat (SAT), 2) diet rich in monounsaturated fat (MUFA) (Mediterranean diet), and 3) diet rich in carbohydrates (CHOs). RESULTS: Weight, body composition, and resting energy expenditure remained unchanged during the three sequential dietary periods. Using dual-energy X-ray absorptiometry we observed that when patients were fed a CHO-enriched diet, their fat mass was redistributed toward the abdominal depot, whereas periphery fat accumulation decreased compared with isocaloric MUFA-rich and high-SAT diets (ANOVA P < 0.05). Changes in fat deposition were associated with decreased postprandial mRNA adiponectin levels in peripheral adipose tissue and lower insulin sensitivity index values from a frequently sampled insulin-assisted intravenous glucose tolerance test in patients fed a CHO-rich diet compared with a MUFA-rich diet (ANOVA P < 0.05). CONCLUSIONS: An isocaloric MUFA-rich diet prevents central fat redistribution and the postprandial decrease in peripheral adiponectin gene expression and insulin resistance induced by a CHO-rich diet in insulin-resistant subjects.

Oxidized-LDL levels are changed during short-term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria.

AIMS: To investigate the role of HMG-CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox-LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers. METHODS: In a double-blind, randomized crossover study, 15 obese diet-treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox-LDL levels were measured fasting and during a euglycaemic-hyperinsulinaemic clamp (approximately 5.5 mmol/l; EHC) and a hyperglycemic clamp (approximately 20 mmol/l; HC). An endothelium-dependent flow-mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S-ICAM, s-VCAM and basal prothrombotic factors were also measured. RESULTS: During cerivastatin treatment, basal circulating ox-LDL levels decreased by 48% (P<0.001) compared with placebo. Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P<0.001) and the increments in FMD correlated with decrements in serum ox-LDL levels (r=0.78, P=0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P<0.05). Basal sICAM-1 and sVCAM-1 levels decreased (P<0.01 and P<0.05, respectively). CONCLUSIONS: In early obese Type 2 diabetic patients, serum ox-LDL levels are influenced by short-term serum glucose variations and lowered with cerivastatin therapy. During cerivastatin treatment, improved flow-mediated endothelium-dependent dilation was associated with decrements in circulating ox-LDL levels and the hyperinsulinaemia-induced urinary albumin excretion was blunted.

Depressed lymphoproliferative response in mixed leukocyte reaction after Mis-locus alloimmunization.

The proliferation of BALB/C lymphocytes preimmunized with Mis or H-2 incompatible cells in response to alloantigens was studied. The results show that preimmunization with Mis-incompatible spleen cells inhibits the lymphoproliferative response against alloantigens whereas preimmunization with H-2 incompatible spleen cells enhances it. It is suggested that Mis coded determinants activate suppressor mechanisms responsible for the unresponsiveness of these preimmunized lymphocytes against alloantigens.

[Temporal cerebellar atrophy following phenytoin therapy]. / Atrofia cerebelosa en relación temporal con la introducción de fenitoína.

Epilepsy is considered among the causes of acquired cerebellar degeneration. It is broadly discussed if its real cause would be seizures, the cerebral hypoxia related to them, or different drugs used in epilepsy treatment, such as phenytoin or carbamazepine. We report on a young male diagnosed of partial seizures and treated with carbamazepine, who began to receive phenytoin after the meningioma removing. He suffered then a progressive cerebellar degeneration according to CT and MR controls during a 18 months follow-up. Serum phenytoin levels were always normal and the patient never presented symptoms related to acute toxicity. We consider phenytoin is the main cause of the cerebellar atrophy noted in our patient; the short time in which it developed makes us think that there is an special susceptibility in cerebellum cells to phenytoin toxicity.

The SstI polymorphism of the apo C-III gene is associated with insulin sensitivity in young men.

AIMS/HYPOTHESIS: Insulin resistance is considered to be a risk factor for diabetes and coronary heart disease and is determined by the interaction between genetic and environmental factors. The SstI polymorphism in the apolipoprotein C-III gene has been related to the presence of different features of the insulin resistance syndrome. We investigate if this mutation influences the peripheral effect of insulin in healthy young subjects (30 men and 29 women) eating a westernised diet. METHODS: We investigated peripheral insulin sensitivity with the insulin suppression test after a 28-day westernised high-saturated fat diet (38% total fat and 18% saturated fat with 115 mg of cholesterol per 1000 Ju). RESULTS: Steady state plasma glucose values were lower in S1-S1 compared with S1-S2 men (p=0.018 by ANOVA), but not in women (p=0.723). CONCLUSION/INTERPRETATION: There was no difference between carriers and non-carriers of the S2 allele in relation to incidence and sensitivity; although on subgroup analysis there was an effect in men but not in women.

A reduction in dietary saturated fat decreases body fat content in overweight, hypercholesterolemic males.

BACKGROUND AND AIM: The effect of the quality of dietary fat on body composition is unknown. Our objective was to determine whether body composition is modified by the isocaloric substitution of a diet rich in saturated fat by a diet high in monounsaturated fat (Mediterranean diet) or a carbohydrate-rich diet in overweight subjects with hypercholesterolemia. METHODS AND RESULTS: The study involved 34 hypercholesterolemic males aged 18-63 years with a body mass index (BMI) of 28.2 (2.6), all of whom consumed a diet rich in saturated fat (SAT) for 28 days. They were then randomly divided into two groups of 17 subjects and underwent two dietary periods of 28 days each in a crossover design: a Mediterranean diet high in monounsaturated fat (MONO) and a carbohydrate-rich diet (CHO). The order of the diets was different for the two group. The CHO diet contained 57% CHO and 28% total fat (< 10% saturated fat, 12% monounsaturated fat and 6% polyunsaturated fat); the Mediterranean diet contained 47% CHO and 38% fat (< 10% saturated fat, 22% monounsaturated fat--75% of which was provided by olive oil- and 6% polyunsaturated fat). The variables measured at the end of each dietary intervention period were: 1) body composition by means of bioelectrical impedance; 2) plasma lipoproteins using enzymatic techniques; and 3) fatty acids in cholesterol esters by means of gas chromatography. BMI and the waist/hip ratio remained the same during the three dietary periods. A decrease in fat was observed when changing from a saturated fat diet (23.3 (6.3) kg) to a Mediterranean diet (20.8 (7.2) kg) (p < 0.05), or a carbohydrate-rich diet (20.6 (6.7) kg) (p < 0.05). Lean mass increased when changing from a SAT diet (58.4 (7.0) kg) to a CHO diet (60.2 (7.0) kg) (p < 0.05). CONCLUSION: The isocaloric substitution of a saturated fat-rich diet by a Mediterranean or carbohydrate-rich diet decreases total body fat in hypercholesterolemic males.