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Postprandial lipid abnormalities are considered an independent cardiovascular risk factor. Hence, it is important to find nutritional strategies that are able to positively influence these abnormalities. Since the effect of n-3 polyunsaturated fatty acids (PUFA) and polyphenols on postprandial lipids in humans is still under debate, we evaluated the acute response of triglyceride-rich lipoproteins to test meals that are naturally rich in polyphenols and/or marine long-chain (LC) n-3 PUFAs. We hypothesized that LC n-3 PUFA would have a different effect on chylomicron and very low density lipoproteins when compared with polyphenols or their combination. We randomly assigned 78 individuals who were at high cardiometabolic risk to 4 isoenergetic diets. These diets only differed in amount of LC n-3 PUFA and/or polyphenols. Prior to starting the intervention, each subject underwent a test meal similar to the type of diet assigned: low in LC n-3 PUFA and polyphenols (control), rich in LC n-3 PUFA and low in polyphenols, rich in polyphenols and low in LC n-3 PUFA, or rich in both. Blood samples were taken before and up to 6 hours after the test meal in order to evaluate cholesterol and triglycerides (plasma and triglyceride-rich lipoprotein), apolipoprotein B-48 (large very low density lipoprotein), glucagon-like peptide-1, and free fatty acid plasma levels. The levels of chylomicron cholesterol and triglyceride in response to the test meal rich in LC n-3 PUFA were significantly higher than after the control meal (P = .037 and P = .018); there was no difference in the other variables. In conclusion, this study indicates that acute administration of marine LC n-3 PUFA increases postprandial chylomicron response in contrast with their lowering chronic effects. These differences underline the importance of understanding the acute and chronic effects of nutritional, as well as of other types of, interventions.

Aims/hypothesis The aim of this work was to investigate hepatic lipid metabolic processes possibly involved in the reduction of liver fat content (LF) observed in patients with type 2 diabetes after an isoenergetic diet enriched in monounsaturated fatty acids (MUFAs). Methods This is an ancillary analysis of a published study. In a parallel-group design, 30 men and eight women, aged 35-70 years, with type 2 diabetes and whose blood glucose was controlled satisfactorily (HbA1c< 7.5% [58 mmol/mol]) by diet or diet plus metformin, were randomised by MINIM software to follow either a high-carbohydrate/high-fibre/low-glycaemic index diet (CHO/fibre diet, n= 20) or a high-MUFA diet (MUFA diet, n= 18) for 8 weeks. The assigned diets were known for the participants and blinded for people doing measurements. Before and after intervention, LF was measured by 1 H-MRS (primary outcome) and indirect indices of de novo lipogenesis (DNL) (serum triacylglycerol palmitic:linoleic acid ratio), stearoyl-CoA desaturase activity (SCD-1) (serum triacylglycerol palmitoleic:palmitic acid ratio) and hepatic ?-oxidation of fatty acids (?-hydroxybutyrate plasma concentrations) were measured. Results LF was reduced by 30% after the MUFA diet, as already reported. Postprandial ?-hydroxybutyrate incremental AUC (iAUC) was significantly less suppressed after the MUFA diet (n = 16) (-2504 ± 4488 ?mol/l × 360 min vs baseline -9021 ± 6489 ?mol/l × 360 min) while it was unchanged after the CHO/fibre diet (n = 17) (-8168 ± 9827 ?mol/l × 360 min vs baseline -7206 ± 10,005 ?mol/l × 360 min, p = 0.962) (mean ± SD, p = 0.043). In the participants assigned to the MUFA diet, the change in postprandial ?-hydroxybutyrate iAUC was inversely associated with the change in LF (r = -0.642, p = 0.010). DNL and SCD-1 indirect indices did not change significantly after either of the dietary interventions. Conclusions/interpretation Postprandial hepatic oxidation of fatty acids is a metabolic process possibly involved in the reduction of LF by a MUFA-rich diet in patients with type 2 diabetes.

The paper presents a post-hoc analysis of the intensity of dyslipidaemia care operated in the first 2 years of Multiple-Intervention-in-type-2-Diabetes.ITaly (MIND.IT) study.MIND.IT is a multicentric, randomized, two-parallel arm trial involving 1461 type 2 diabetic patients at high cardiovascular (CV) risk. The study compares the usual care (UC) of CV prevention with a multifactorial intensive care (IC) approach aiming at achieving target values for the main CV risk factors according to a step-wise treat-to-target approach.Proportion of patients on target for low-density lipoprotein cholesterol (LDL-C) was about 10% at baseline and increased significantly more with IC than UC (43 vs. 27%; p 0.001). However, the majority (57%) of patients, in this intended intensively treated cohort, failed to achieve the proposed target. Average LDL-C decreased from 144 ± 35 to 108 ± 31 mg/dl with IC and from 142 ± 28 to 118 ± 32 with UC (p-for-interaction0.0001). IC was associated with a significantly greater increase in statin prescription and lower withdrawal from treatment than UC (43 vs. 11% and 28 vs. 61%, respectively; both p 0.001). However, the new treatments were characterized in both groups by the use of low starting doses (≤ 10 mg of atorvastatin, equivalent dose in more than 90% of patients) without increase in case of missed target.The application of a multifactorial treat-to-target intervention is associated with a significant improvement in LDL-C beyond usual practice. However, the change in LDL-C appears to be more related to an increased number of treated patients and a decreased treatment withdrawal than to a true treat-to-target approach.

The aim of the study was to evaluate whether two dietary approaches recommended for diabetes mellitus and cardiovascular prevention-high-MUFA or complex carbohydrates/fiber-differently influence inflammation. A 4-week crossover study in 12 individuals with type 2 diabetes was performed. Fasting and postprandial hs-CRP plasma levels were not significantly different after a high-carbohydrate/high-fiber/low-glycemic index (CHO/fiber) and a high-MUFA diet. Compared with fasting, hs-CRP levels decreased significantly after the MUFA but not after the CHO/fiber meal. Triglyceride-rich lipoproteins were significantly lower after the CHO/fiber than the MUFA diet. At fasting and postprandially, hs-CRP correlated with triglyceride in whole plasma, chylomicrons, small and large VLDL after the CHO/fiber but not after the MUFA diet. In conclusion, a MUFA-rich diet and a carbohydrate/fiber-rich diet induced similar effects on plasma hs-CRP concentrations. However, these dietary approaches seem to influence hs-CRP levels through different mechanisms. i.e., direct acute postprandial effects by MUFA and triglyceride-rich lipoproteins mediated effects by CHO/fiber.

The aim of this study was to evaluate exogenous and endogenous lipoprotein responses to a standard fat-rich meal in type 2 diabetic patients with optimal fasting triglyceridemia and optimal blood glucose control. Seven type 2 diabetic patients and five nondiabetic controls (age, 49 +/- 7 and 48 +/- 4 yr; body mass index, 28.3 +/- 3.6 and 25.1 +/- 3.6 kg/m(2); mean +/- SD) were given, after at least 12 h of fasting, a standard fat-rich meal. Before and over the 6 h after the meal, serial blood samples were taken for determination of glucose, insulin, lipids, lipoproteins, apolipoprotein B-48 (apo B-48), apo B-100, free fatty acids, and lipoprotein lipase activity. The main abnormality in the postprandial lipid response of diabetic patients involved large very low density lipoproteins. In these particles, apo B-48, apo B-100, cholesterol, and triglyceride incremental areas were, in fact, significantly higher in diabetics compared with controls [7.08 +/- 2.65 vs. 1.17 +/- 0.88 mg/liter.h, 65.5 +/- 11.5 vs. 12.4 +/- 1.77 mg/liter.h, 29.7 +/- 3.9 vs. 13.1 +/- 3.1 mg/dl.h (0.77 +/- 0.10 vs. 0.34 +/- 0.08 mmol/liter.h), 170 +/- 31 vs. 94 +/- 22 mg/dl.h (1.93 +/- 0.35 vs. 1.06 +/- 0.25 mmol/liter.h)] (all P0.05; mean +/- SEM). Postprandial preheparin lipoprotein lipase plasma activity was, if anything, higher in diabetic patients. In conclusion, even with fasting normotriglyceridemia and optimal blood glucose control, type 2 diabetic patients are characterized, in the postprandial period, by a significant increase in large very low density lipoproteins of both endogenous and exogenous origins.

SCOPE: Dysregulation of lipid homeostasis is related to multiple major healthcare problems. The aim of this study was to investigate the effects of n-3 fatty acid (FA) and polyphenol rich diets on plasma and HDL fraction lipidomic profiles in subjects at high cardiovascular risk. METHODS AND RESULTS: Ultra performance LC coupled to quadrupole TOF/MS mass spectrometry global lipidomic profiling was applied to plasma and HDL fraction from an 8 wk randomized intervention with four isoenergetic diets, differing in their natural n-3 FA and polyphenols content, in 78 subjects with a high BMI, abdominal obesity, and at least one other feature of the metabolic syndrome. Dependency network analysis showed a different pattern of associations between lipidomics, dietary, and clinical variables after the dietary interventions. The most remarkable associations between variables were observed after the diet high in n-3 FA and polyphenols, as the inverse association between gallic acid intake and LDL cholesterol levels, which was indirectly associated with a HDL cluster exclusively comprised lysophospholipids. CONCLUSION: This is the first human randomized controlled trial showing direct and indirect associations with lipid molecular species and clinical variables of interest in the evaluation of the metabolic syndrome after diets naturally rich in polyphenols.

In view of the high incidence of macrovascular diseases in patients with type 2 diabetes mellitus and microalbuminuria, the study evaluates the association of microalbuminuria with fasting plasma Apo B48 levels, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic. We studied 50 patients with type 2 diabetes aged 35–75 years. Exclusion criteria were overt macrovascular disease, overt nephropathy (Glomerular filtration rate (GFR)

Objective: To assess whether a diet containing foods enriched with beta-glucans (3.6 g/d), folic acid (1600 mu g/d), long-chain (800 mg/d) and short-Chain (400 mg/d) n-3 fatty acids, and tocopherols (120 mg/d) is able to modulate positively the cardiovascular risk profile in people at slightly increased cardiovascular risk. Methods: Sixteen subjects with mild plasma lipid abnormalities were studied according to a randomized crossover design. After a 2-week run-in period, they followed a diet containing baked products enriched with active nutrients (active diet) or a diet containing the same products but without active nutrients (control diet) for 1 month and then crossed over to the other diet. At the end of each period, a test meal of the same composition as the corresponding diet was administered, and plasma samples were obtained before and for 6 hours after the meal. Hunger and satiety were evaluated by the visual analog scale at fasting and after the meal. Results: Fasting plasma triglycerides were significantly lower after the active versus the control diet (1.56 +/- 0.18 vs 1.74 +/- 0.16 mmol/l, p < 0.05), as was the postprandial level of chylomicron triglycerides and the insulin peak (p < 0.05). The active diet also reduced fasting homocysteine (8 +/- 0.6 vs 10 +/- 0.8 mu mol/l, p < 0.05) and the feeling of hunger at the fifth and sixth hour (p < 0.05). Conclusions: Baked functional products enriched with n-3 fatty acids, folates, beta-glucans, and tocopherols within the context of a balanced diet lower fasting and postprandial plasma triglycerides, fasting homocysteinemia, and the postprandial insulin peak. They induce a greater feeling of satiety with possible beneficial implications on energy intake.

BACKGROUND AND AIM: The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form. METHODS AND RESULTS: Fifteen healthy individuals (12 M/3 F), mean age 54.5+/-7.6 years, BMI 27.4+/-3.0 kg/m(2) (mean+/-SD), participated in a randomized sequential crossover study. After 2 weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8 g/day). After the two treatment periods (each lasting 3 weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (-4.3%; p

We investigated postprandial plasma and adipose tissue (AT) adiponectin changes in relation to obesity and type 2 diabetes mellitus. Fasting and 6 hours after a standard fat-rich meal blood samples (adiponectin, glucose, insulin, lipids) and needle biopsies of abdominal subcutaneous AT (adiponectin messenger RNA, lipoprotein lipase activity) were taken in 10 obese diabetic (OD), 11 obese nondiabetic (OND), and 11 normal-weight control (C) men. The OD and OND subjects had similar adiposity (body mass index, waist circumference) and insulin resistance (hyperinsulinemic euglycemic clamp). Fasting plasma adiponectin and AT gene expression were not significantly different between groups. After meal, plasma adiponectin decreased in OD but significantly increased in OND and C, the changes being significantly different between groups (analysis of variance, P = .01); adiponectin messenger RNA decreased in OD (-0.27 +/- 0.25 AU, P = .01) but was unchanged in OND (P = .59) and C (P = .45). After meal, plasma adiponectin correlated inversely with triglyceride and cholesterol concentrations in chylomicrons and large very low-density lipoprotein, and directly with AT lipoprotein lipase activity (P < .05 for all). Type 2 diabetes mellitus is associated with lower postprandial plasma levels and AT gene expression of adiponectin independently of degree of adiposity and whole-body insulin sensitivity. In patients with diabetes, this may exacerbate postprandial abnormalities of lipoprotein metabolism.

BACKGROUND Post-prandial lipid abnormalities might contribute to the excess of cardiovascular risk typical of type 2 diabetic patients. The study evaluated the effects of atorvastatin (20 mg d(-1)) vs. fenofibrate (200 mg d(-1)) on post-prandial lipids in type 2 diabetic patients with mixed hyperlipidaemia. MATERIALS AND METHOD Eight type 2 diabetic patients, male/female (M/F) 6/2, age 58 +/- 5 years, body mass index (BMI) 28 +/- 3 kg m(-2) with cholesterol of low-density lipoprotein (LDL) between 100-160 mg dL(-1) and triglycerides between 150-400 mg dL(-1), participated in a randomized, cross-over study (3 months on atorvastatin and 3 months on fenofibrate). At baseline and at the end of the two treatments, the patients were given a standard fat meal; blood samples were taken before the meal and every 2 h after for the assay of cholesterol, triglycerides, apoB-48 and apoB-100 (determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis) in plasma lipoproteins and very low-density lipoprotein (VLDL) subfractions (large and small VLDL), separated by density gradient ultracentrifugation. RESULTS Data on fasting lipids confirmed that atorvastatin was more effective on the reduction of LDL-cholesterol, whereas fenofibrate was a better triglyceride-lowering agent. Concerning the post-prandial phase, the incremental areas under the curve (IAUC) for chylomicrons and large VLDL were reduced after both treatments, reaching statistical significance for cholesterol, triglyceride and apoB-100 content of chylomicrons only after fenofibrate administration [IAUC, (5.2 +/- 4.6 vs. 10.7 +/- 9.3) mg dL(-1) h(-1), P = 0.03; (131.3 +/- 95.1 vs. 259.1 +/- 201.5) mg dL(-1) h(-1), P = 0.02; (0.46 +/- 1 vs. 3 +/- 3.7) mg dL(-1) h(-1), P = 0.025, all respectively]. CONCLUSIONS During the post-prandial state fenofibrate appeared to be more effective than atorvastatin in reducing the chylomicron response.

Background: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. Aim: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. Design: A randomized double-blind sequential cross-over study. Subjects and methods: Thirty subjects of both genders (20 M/10 F), mean age 45.5±9.9 years (M±SD), BMI 26.6±2.2 kg/m2, with plasma cholesterol >5.17 and

Objective— To evaluate the role of insulin resistance in development of postprandial dyslipidemia in type 2 diabetic patients in an experimental setting in which these patients were compared with nondiabetic subjects at similar glucose and insulin blood levels. Methods and Results— Eight type 2 diabetic patients in optimal blood glucose control and 7 control subjects (aged 50.0±2.6 and 48.1±1.3 years; body mass index 28.3±1.2 and 25.6±1.1 kg/m 2 ; fasting plasma triglycerides 1.12±0.13 and 0.87±0.08 mmol/L, respectively; mean±SEM; NS) consumed a mixed meal during an 8-hour hyperinsulinemic glycemic clamp. Mean blood glucose during clamp was ≈7.8 mmol/L, and plasma insulin during the preprandial steady state was ≈480 pmol/L in both groups, that differed for insulin sensitivity (M/I value lower in diabetic subjects [1.65±0.30 and 3.42±0.60; P P P P Conclusions— Insulin resistance is also associated with postprandial lipoprotein abnormalities in type 2 diabetes after acute correction for hyperglycemia and hyperinsulinemia.

Normolipidaemic insulin-dependent diabetic (IDDM) patients are characterized by an increase in the smaller VLDL particles, considered to be the most atherogenic. Since blood glucose control is one of the main regulators of lipid metabolism in diabetic patients, it could influence the shift in the distribution of VLDL subfractions towards smaller particles. To evaluate this possibility, VLDL subfractions, post-heparin lipoprotein lipase and hepatic lipase activities have been evaluated in male IDDM patients with either unsatisfactory blood glucose control (group 1, HbA1c8%, n = 18) or good blood glucose control (group 2, HbA1c8%, n = 16) and in 16 normoglycaemic individuals. The three groups were comparable for sex, age, body mass index, and plasma lipid levels. Three VLDL subfractions (large, Svedberg flotation unit (Sf) 175-400; intermediate, Sf 100-175; small, Sf 20-100) were separated by density gradient ultracentrifugation and analysed for cholesterol, triglyceride, and phospholipid levels. When compared to control subjects both groups of IDDM patients showed a clear shift in VLDL subfraction distribution with a significant increase in the proportion of small VLDL (group 1; 49 +/- 2%; p0.005; group 2: 51 +/- 3%, p0.01; control subjects 40 +/- 2%) (mean +/- SEM) in relation to total VLDL. By contrast, the absolute lipid concentration of small VLDL was higher only in group 1, compared to control subjects (35 +/- 4 vs 27 +/- 3 mg/dl, p = 0.05). Post-heparin hepatic lipase activity was significantly reduced in both IDDM groups (group 1: 254 +/- 19 mU/ml, p0.05; group 2: 202 +/- 19 mU/ml, p0.005; control subjects 317 +/- 31 mU/ml). In conclusion, normolipidaemic IDDM patients show an increase in the smallest VLDL, whatever their degree of blood glucose control. However, this abnormality may be clinically relevant only in patients with unsatisfactory blood glucose control, since absolute lipid concentration of these potentially atherogenic particles is only increased in this group.

Very low density lipoproteins (VLDL) have an abnormal lipid composition in Type 1 (insulin-dependent) diabetic patients. Since VLDL represent a heterogeneous lipoprotein class, this might be due either to a shift in the distribution or to an abnormal composition of VLDL subclasses or both. In order to investigate these possibilities and to evaluate possible pathogenetic mechanisms, lipid composition (non-esterified and esterified cholesterol, triglycerides, phospholipids) of four VLDL subfractions of decreasing size (A: Svedberg flotation unit [Sf]>400, B: Sf, 175–400, C: Sf 100–175, D: Sf 20–100), isolated by density gradient preparative ultracentrifugation, and plasma post-heparin lipolytic activity (lipoprotein lipase and hepatic lipase) were evaluated in 13 male normolipidaemic insulin-dependent diabetic patients in good glycaemic control (HbA1c 6.9±0.5%) (mean±SEM) and 9 male control subjects matched for age, body mass index and plasma lipid values. Compared to control subjects, diabetic patients showed a reduced total lipid concentration of VLDL of intermediate size (B and C) reaching statistical significance only for VLDL C (0.16±0.02 vs 0.24±0.03 mmol/l; p

Background The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT) of subjects with both obesity and type 2 diabetes (OBT2D), characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB). Design and Methods The levels of anandamide and 2-AG, and of the anandamide-related PPARα ligands, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW) subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp. Results As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p < 0.05), and 2-AG levels 2.3-fold reduced (p < .05), in OBT2D but not in OB subjects. Anandamide, OEA and PEA correlated positively (p < .05) with SAT leptin mRNA and free fatty acid during hyperinsulinaemic clamp, and negatively with SAT LPL activity and plasma HDL-cholesterol, which were all specifically altered in OBT2D subjects. Conclusions The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners) and 2-AG in obesity and type 2 diabetes.

Lipid and apoprotein composition of four very low density lipoprotein (VLDL) subfractions decreasing in Sf value were evaluated in the fasting state in 12 normolipidemic Pima Indians (6 M, 6 F, age 39 +/- 1.7 yrs) (mean +/- SEM) with non-insulin-dependent diabetes mellitus (NIDDM) in poor glycemic control (HbA1 9.8 +/- 2.9%) and in 14 normoglycemic Pima controls matched for age, BMI and lipid values. Total cholesterol (CHOL), triglyceride (TG), phospholipids (PL), total protein (TP), apo B, apo CII, apo CIII and apoE were assayed in total VLDL and in each of the four VLDL subfractions designed as A (Sf greater than 400), B (Sf 175-400), C (Sf 100-175), and D (Sf 20-100). Diabetics compared to nondiabetics had higher concentrations of all constituents of VLDL D, with the largest changes being in TG (38.0 +/- 3.8 vs 28.0 +/- 2.5 mg/dl, P less than 0.04), PL (14.0 +/- 1.3 vs 10.0 +/- 1.0 mg/dl, P less than 0.04), TP (9.8 +/- 0.8 vs 7.6 +/- 2.4 mg/dl, P less than 0.05), apo B (6.3 +/- 0.5 vs 4.7 +/- 0.4 mg/dl, P less than 0.03) and apoE (0.73 +/- 0.09 vs 0.52 +/- 0.04 mg/dl, P less than 0.04). Since no difference was found between the groups in percentage composition of lipids or apoproteins in total VLDL and in all VLDL subfractions, the data suggest that in diabetics, even when normolipidemic, there is an increase in the number rather than in the composition of the smallest VLDL subfraction (VLDL D), which are usually considered to be more atherogenic.

Eight type II (non-insulin-dependent) normolipidemic diabetic patients (aged 45 +/- 15 yr, body mass index 22 +/- 2 kg/m2, means +/- SD) treated with diet alone or diet plus oral hypoglycemic agents were given, in random order for periods of 15 days, two diets with different carbohydrate (CHO) (40 vs. 60% of total calories) and fat (20 vs. 40%) levels. Simple CHO, fiber, saturated fat, cholesterol, and polyunsaturated-saturated fat ratio were similar in the two diets. Total plasma cholesterol was not significantly affected by dietary changes; conversely, plasma triglyceride (1.38 +/- 0.59 vs. 1.11 +/- 0.39 mM, P less than 0.05) and apolipoprotein CII (3.8 +/- 1.4 vs. 3.3 +/- 0.8 mg/dl) increased significantly after the high-CHO low-fat diet. Among the various lipoproteins, very-low-density lipoprotein (VLDL) was the most affected by diet: VLDL cholesterol concentrations increased from 0.30 +/- 0.19 to 0.43 +/- 0.28 mM (P less than 0.05), and triglyceride concentrations increased from 0.62 +/- 0.33 to 0.88 +/- 0.53 mM (P less than 0.05). In conclusion, increasing the amount of complex CHO in the diet induces an elevation of VLDL in normolipidemic, nonobese, mildly type II diabetic patients.

Although it has been reported that bezafibrate influences carbohydrate metabolism, this possibility has never been properly evaluated in a controlled clinical trial. In this study we attempted to evaluate the effects of bezafibrate on plasma lipoproteins, glucose tolerance, insulin secretion and peripheral insulin sensitivity in a group of hypertriglyceridemic patients with and without diabetes. Sixteen hyperlipidemic patients (10 males and 6 females) participated in the study. Eight had type IIB and 8 type IV hyperlipoproteinemia; 6 of them also had non-insulin dependent diabetes mellitus. The study was performed according to a double blind, crossover design: after 1 month wash-out period in which patients were on diet alone, they underwent, in a random order, a period of placebo therapy and another period in which they received a single daily dose of a long-acting bezafibrate preparation (400 mg) administered in the evening. Each treatment lasted 2 months. Total plasma and VLDL triglyceride concentrations were consistently reduced by bezafibrate (-46%, P less than 0.001; and -50%, P less than 0.001). Total and VLDL-cholesterol were also reduced by bezafibrate. The effects of bezafibrate on lipoproteins were similar in diabetic and non-diabetic subjects. Bezafibrate treatment did not influence fasting blood glucose concentration, glucose tolerance, peripheral insulin sensitivity or insulin secretion. In conclusion, the results of this controlled trial clearly indicate that bezafibrate can be successfully employed to lower plasma lipid levels in patients with non-insulin dependent diabetes mellitus and hyperlipidemia.

Common and internal carotids have been studied by noninvasive method (echo-Doppler) in 30 normotensive patients with familial hypercholesterolemia (FH). Vascular lesions were detected in 14 patients (46%), who presented one or more lesions of different degree (between 1-15% and 16-49%). In one case, only one carotid had stenosis greater than 50%. Severity and number of stenosis were related to age and levels of hypercholesterolemia. FH patients with carotid lesions showed a significantly higher LDL-cholesterol (p less than 0.01) and plasma apolipoprotein B (p less than 0.001) concentrations and a significantly lower HDL-cholesterol (p less than 0.05) and plasma apolipoprotein A (p less than 0.001) levels as compared to those with normal echo-Doppler findings. These data indicate that investigation of arterial districts other than coronaries are useful in quantitative evaluation of atherosclerotic involvement.

Changes in plasma lipoprotein pattern, with particular attention to high density lipoprotein cholesterol (HDL-C) concentration, were evaluated in 7 (5 female, 2 male) obese patients before and 15 +/- 1 months after they had lost weight (mean 20.7 +/- 3.1 kg), when the patients' food intake had been ad libitum for at least 6 months, and they had been maintaining their weight loss. Plasma low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein triglyceride (VLDL-TG) concentrations were lower than baseline values: on the other hand, plasma HDL-C concentration, which was below normal values before weight reduction, was found to be significantly increased (P < 0.05). These data indicate that, among the favourable changes in plasma lipoprotein pattern, an increase in HDL-C may be achieved after remarkable and stable weight loss in severe obesity.

Arterial blood flow to different tissues and organs is influenced by blood viscosity. The main determinants of blood viscosity are hematocrit and plasma protein concentration. Venesection and consequent reduction of hematocrit are very useful in various pathological conditions. Plasma-exchange removes proteins in excess (such as LDL in familial hypercholesterolemia) from plasma and thereby improves plasma viscosity, erythrocyte deformability and blood flow to the body tissues.

Plasma lipoprotein compositional abnormalities were investigated in eight normolipidaemic (plasma cholesterol

AIM: Obesity is associated with an altered GH/IGF-I axis status, accounting for the increased cardiovascular risk in obese subjects with GH deficiency. Aim of this randomized, simple-blind, cross-over study was to verify the effectiveness of a short-term treatment with orlistat in reducing non-esterified fatty acid (NEFA) and influencing the endogenous activity of GH/IGF-I axis in obese subjects. OUTCOME MEASURES: The primary outcome measures were post-prandial lipemia; GH peak after GHRH+arginine; IGF-I; IGF-binding protein (BP)-3, IGF-I/IGFBP-3 ratio. Secondary outcome measures were insulin resistance (IR) indexes (homeostasis model assessment of insulin resistance and Insulin Sensitivity Index). STUDY DESIGN: Twenty obese post-menopausal women (age: 53.6 ± 6.2; body mass index: 34.1 ± 4.0) were randomized to receive normo-caloric diet plus + orlistat (Roche, UK; 120 mg tid) or normo-caloric diet without the additional treatment. The duration of follow-up was 10 days for each treatment period. RESULTS: Orlistat induced a weight-independent reduction in post-prandial NEFA levels compared with diet alone, with higher GH peak, IGF-I, and IGF-I/IGFBP3 ratio. GH peak was correlated negatively with postprandial NEFA and positively with IGF-I and IGF-I/IGFBP-3 ratio. CONCLUSIONS: Orlistat is effective in inducing a weight-independent higher reduction in post-prandial NEFA levels than dietary treatment alone along with increase in GH peak, IGF-I levels, and IGFI/ IGFBP-3 ratio. These results might add a new potential benefit of orlistat in the management of obese subjects.

We investigated the serum fatty acid profiles of cholesterol esters, phospholipids and triglycerides in 24 patients with Friedreich's disease and 16 patients with other forms of spinocerebellar degeneration. In 8 patients with Friedreich's disease we also analyzed the fatty acid profile of the lipoprotein fractions. We found no major differences in fatty acid profiles between ataxic patients and sex and age-matched controls; in particular there was no decrease of linoleic acid in Friedreich's disease. The level of linoleic acid in serum cholesterol esters decreased with increasing disability of patients.