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Osteoarthritis (OA) is a debilitating and heterogeneous condition, characterized by various levels of articular cartilage degradation, osteophytes formation, and synovial inflammation. Multiple evidences suggest that synovitis may appear early in the disease development and correlates with disease severity and pain, therefore representing a relevant therapeutic target. In a typical synovitis-driven joint disease, namely rheumatoid arthritis (RA), several pathotypes have been described by our group and associated with clinical phenotypes, disease progression, and response to therapy. However, whether these pathotypes can be also observed in the OA synovium is currently unknown. Here, using histological approaches combined with semi-quantitative scoring and quantitative digital image analyses, we comparatively characterize the immune cell infiltration in a large cohort of OA and RA synovial tissue samples collected at the time of total joint replacement. We demonstrate that OA synovium can be categorized also into three pathotypes and characterized by disease- and stage-specific features. Moreover, we revealed that pathotypes specifically reflect distinct levels of peripheral inflammation. In this study, we provide a novel and relevant pathological classification of OA synovial inflammation. Further studies investigating synovial molecular pathology in OA may contribute to the development of disease-modifying therapies. [ABSTRACT FROM AUTHOR]

• Serum cholesterol ester fatty acids (FA) reflect dietary FA intake. • Myristic and pentadecanoic acids were associated with saturated fat intake. • Oleic acid was associated with monounsaturated fat intake. • Fish oil induced a marked increase in eicosapentaenoic and docosahexaenoic acids. • Δ-9 desaturase activity was more reduced after the MUFA diet than the SFA diet. The effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake. To evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters. In a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements. Main differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, p<0.0001) than SFA diet (0.31±0.09 vs 0.29±0.08, p=0.006), with a statistically significant difference between the two groups (p<0.0001). This study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation. [ABSTRACT FROM AUTHOR]

Background and Aims: Aleurone is the innermost layer of wheat bran, rich in fiber, minerals, vitamins, phenolic compounds, and betaine. The metabolic effects of aleurone rich foods are still unknown. Our aim was to investigate the effects of consuming a Wheat Aleurone rich diet vs. a Refined Wheat diet for 8 weeks on fasting and postprandial glycemic and lipid metabolism, inflammation, and oxidative stress in overweight/obese individuals.Methods and Results: According to a randomized cross-over study design, 23 overweight/obese individuals, age 56 ± 9 years (M±SD), were assigned to two isoenergetic diet - Wheat Aleurone and Refined Wheat diets - for 8 weeks. The diets were similar for macronutrient composition but different for the aleurone content (40-50 g/day in the Wheat Aleurone diet). After each diet, fasting and postprandial plasma metabolic profile, ferulic acid metabolites and 8-isoprostane concentrations in 24-h urine samples were evaluated. Compared with the Refined Wheat Diet, the Wheat Aleurone Diet increased fasting plasma concentrations of betaine by 15% (p = 0.042) and decreased the excretion of 8-isoprostane by 33% (p = 0.035). Conversely, it did not affect the fasting and postprandial glucose, insulin and triglyceride responses, homocysteine, and C-Reactive Protein concentrations, nor excretion of phenolic metabolites.Conclusion: An 8-week Wheat Aleurone Diet improves the oxidative stress and increases plasma betaine levels in overweight/obese individuals with an increased cardiometabolic risk. However, further studies with longer duration and larger sample size are needed to evaluate the benefits of aleurone-rich foods on glucose and lipid metabolism in individuals with more severe metabolic abnormalities.Clinical Trial Registry Number: NCT02150356, (https://clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Epidemiological evidence has confirmed the potential causal relationship between specific dietary factors and non-communicable diseases. However, currently nutrition was shown to be insufficiently integrated into medical education, regardless of the country. Without an adequate nutrition education, it is reasonable to assume that future physicians, as well as other health care professionals, will be not able to provide the highest quality care to patients in preventing and treating non-communicable diseases. Furthermore, the insufficient availability of physicians with specializations in nutrition has posed the basis for the development of non-medical careers in the field of nutrition. The present document was drafting by the Italian College of Academic Nutritionists, MED-49 (ICAN-49), with the aim to provide an overview on the nutritional competency standards covered by several health care professionals (Physicians Clinical Nutrition Specialists, Clinical Dietitians, Professional Clinical Nutrition Specialists, etc) for the prevention of diseases and/or support of pharmacological therapies. The aim of the ICAN 49 is to suggest a major shift in practice opportunities and roles for many nutritionists, especially for the management of the metabolic diseases, and promote a paradigm change: a clinical and educational leadership role for Physician Clinical Nutrition Specialists in the hospital setting. [ABSTRACT FROM AUTHOR]

Background Plasma trimethylamine N-oxide (TMAO) has drawn much attention as a marker of several chronic diseases. Data on the relation between diet and TMAO are discordant and few human intervention studies have assessed causality for this association. Objectives We aimed to evaluate the effects on plasma TMAO of diets based on foods rich in polyphenols (PP) and/or long-chain n–3 fatty acids (LCn3) or whole-grain cereals (WGCs), in individuals at high cardiometabolic risk. Methods An ancillary study was performed within 2 randomized controlled trials, aimed at evaluating the medium-term effects on cardiometabolic risk factors of diets naturally rich in PP and/or LCn3 (Etherpaths Project) or WGCs (HealthGrain Project). Results In the Etherpaths study (n = 78), the changes in TMAO (8-wk minus baseline) were statistically significant for the diets rich in LCn3 (+1.15 ± 11.58 μmol/L) (P = 0.007), whereas they were not for the diets rich in PP (−0.14 ± 9.66 μmol/L) (P  = 0.905) or their interaction (P  = 0.655) (2-factor ANOVA). In the HealthGrain Study (n  = 48), the TMAO change (12-wk minus baseline) in the WGC group (+0.94 ± 3.58 μmol/L) was significantly different from that in the Refined Cereal group (−1.29 ± 3.09 μmol/L) (P  = 0.037). Considering the pooled baseline data of the participants in the 2 studies, TMAO concentrations directly correlated with LCn3, EPA (20:5n–3), and protein intake, but not SFAs, fiber, MUFAs, and PP intake. Among food groups, TMAO directly correlated with the intake of fish, vegetables, and whole-grain products, but not meat, processed meat, and dairy products. Conclusions Diets rich in LCn3 of marine origin or WGCs significantly increased plasma TMAO concentration. These changes mirrored the direct associations between TMAO concentrations and intakes of fish and WGCs, suggesting that TMAO reflects intakes of these healthy foods and, therefore, it is not a universally valid biomarker of cardiometabolic risk independent of the background diet. These trials were registered at clinicaltrials.gov as NCT01154478 and NCT00945854. [ABSTRACT FROM AUTHOR]

Background and Aims: Wholegrain cereals have been implicated in the reduction of lifestyle-related chronic diseases risk including cardiovascular diseases and type 2 diabetes. Molecular mechanisms responsible for the beneficial health effects are not entirely understood. The aims of this study were 1) to identify new potential plasma biomarker candidate metabolites of wholegrain cereal foods intake and 2) to examine whether some putative metabolites associated with wholegrain foods intake may play a role in the improvement of cardiometabolic risk factors.Methods and Results: Analysis have been conducted in 54 individuals with metabolic syndrome of both genders, age 40-65 years, randomly assigned to 2 dietary interventions lasting 12-week: 1) wholegrain enriched diet (n = 28), and 2) refined-wheat cereals diet (control diet) (n = 26). Nontargeted metabolite profiling analysis was performed on fasting plasma samples collected at baseline and at the end of the experimental diets. Our data show that, at the end of the intervention, a higher intake of wholegrain (tertile 3) was significantly associated with a marked increase in several lipid compounds, as PC (20:4/16:1), LPC (20:4), LPC (22:6), LPC (18:3), LPC (22:5), and a phenolic compound (P < .05 for all). In the wholegrain group, higher concentrations of these metabolites (tertile 3 vs tertile 1 of each metabolite) were significantly associated with lower postprandial insulin and triglyceride responses (P < .05) by 29% and 37%, respectively.Conclusion: These observations suggest a possible role of lipid and polyphenol metabolites in the postprandial metabolic benefits of wholegrains in subjects at high risk of cardiovascular disease. In addition, they provide insight into the role of these metabolites as potential candidate biomarkers of wholegrain foods. The study was registered on ClinicalTrials.gov (identifier: NCT00945854). [ABSTRACT FROM AUTHOR]

Postprandial metabolic abnormalities are considered important and independent risk factors for cardiovascular diseases. However, the effects of the Mediterranean diet on postprandial metabolism and the mechanism underpinning the effects on clinical variables have not been exhaustively explored. Therefore, the aims of the present study were to evaluate the acute and medium-term effects (8 weeks) on postprandial glucose and lipid metabolism of a diet resembling a typical Mediterranean diet (Med-D) compared to a western-type diet (Control-D), and the mechanisms underlying those effects. Twenty-nine overweight/obese individuals of both genders, aged 20–60 years, were enrolled and randomly assigned to two isoenergetic dietary interventions: 1) a Med-D (n = 16), and 2) a Control-D (n = 13). Adherence to the dietary interventions was assessed by a 7-day food record. A meal test resembling the assigned diet was performed at baseline and after 8 weeks of intervention. Blood samples at fasting and over 4-h after the meal were collected to assess metabolic parameters and short chain fatty acid (SCFA) levels. Fecal samples were also collected to evaluate the microbiota composition. Glucose and insulin responses were significantly reduced at baseline after the Med test meal compared to the Control meal (p < 0.05) and this effect was strengthened after 8 weeks of intervention with the Mediterranean diet (p < 0.05); together with an improvement in OGIS. At the end of the intervention, postprandial plasma butyric acid incremental area under the curve (IAUC) was significantly increased in the Med-D group (p = 0.019) and correlated inversely with plasma insulin IAUC and directly with oral glucose insulin sensitivity (OGIS) (r: −0.411, p = 0.046 and r: 0.397, p = 0.050 respectively). These metabolic changes were accompanied by significant changes in gut microbiota, such as an increase in the relative abundance of Intestinimonas butyriciproducens and Akkermansia muciniphila (p < 0.05) in the Med-D compared to Control-D group. Our study provides strong evidence that a diet resembling the traditional Med-D improves postprandial glucose metabolism and insulin sensitivity. Furthermore, the study highlights a possible involvement of gut microbiota metabolites - such as butyric acid, and of dietary fiber as a precursor - in improving glucose metabolism and insulin sensitivity. [ABSTRACT FROM AUTHOR]

Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters. Twelve healthy men, aged 20–40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low–polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites. Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC 0–5h) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (S I) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = −0.604; p = 0.032) and positively with the S I index (r = 0.588, p = 0.037). RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. NCT02865278. [ABSTRACT FROM AUTHOR]

Background and Aims: Overweight/obesity is a clinical concern also in patients with Type 1 diabetes (T1DM). These patients' body weight may vary depending on whether treatment consists in continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI), as these treatments lead to different blood glucose control, insulin doses, and eating behaviors. We compared long-term body weight trajectories in persons with diabetes on CSII or MDI regimens.Methods and Results: Annual changes in body weight, HbA1c, and daily insulin doses over 6-10 years were retrospectively analyzed in T1DM adult patients on CSII (n = 90) or MDI (n = 90), strictly matched for sex, age, BMI, and diabetes duration. Mean follow-up was 9.1 ± 1.4 years. Body weight increased linearly (∼0.5 kg per year) throughout the observation period (p = 0.001, repeated measures ANOVA) with no significant difference between the CSII and MDI cohorts (p = 0.74), in either normal-weight or overweight/obese patients. HbA1c over follow-up was lower with CSII than with MDI (p = 0.037), maintaining the initial reduction after starting pump therapy. Insulin doses over follow-up were stably lower than baseline (∼20%) with CSII, while linearly increasing (∼20% from baseline to the end of observation) with MDI (p = 0.002). Mean annual weight changes correlated directly with total insulin dose changes (r = 0.191; p = 0.011) and baseline HbA1c level (r = 0.267; p = 0.001), and inversely with HbA1c changes (-0.173; p = 0.021) and baseline age (r = -0.254; p = 0.001).Conclusion: T1DM patients on CSII or MDI showed comparable body weight gain over a 10-year follow-up, despite improved glycemic control and decreased insulin doses with CSII. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic evidence suggests that diets rich in whole grains are associated with a reduced risk of developing chronic diseases and all-cause mortality. However, the molecular mechanisms behind these beneficial metabolic effects are poorly understood. Objective: Our aim was to investigate novel trimethylated (betainized) compounds from mice and humans, and their association with whole grain-rich diets and insulin resistance and insulin secretion. Design: Fasting plasma samples were obtained in a mouse (C57BL/6J male) feeding trial and a controlled dietary intervention. The mouse trial involved feeding the mice a rye and wheat bran-enriched feed which was compared with a high-fat diet. In the human trial, participants recruited from Kuopio, Finland (n = 69) and Naples, Italy (n = 54) with characteristics of the metabolic syndrome were randomly assigned to either a whole grain-enriched diet or a control diet for 12 wk. Plasma concentrations of betainized compounds were analyzed with the use of liquid chromatographytandem mass spectrometry. Insulin resistance and insulin secretion were assessed in an oral-glucose-tolerance test and a meal-glucosetolerance test. Results: The betaines that were increased in mouse plasma after bran-enriched feeding were identified de novo via chemical synthesis and liquid chromatography-tandemmass spectrometry, and confirmed to be associated with an increased intake of whole-grain products in humans. In particular, the concentrations of pipecolic acid betaine were increased at the end of thewhole-grain intervention in both the Kuopio cohort (P < 0.001) and the Naples cohort (P < 0.05), and these concentrations inversely correlated with the postprandial glucose concentration. Furthermore, the concentration of valine betaine was substantially increased during the intervention in Naples (P < 0.001) with an inverse correlation with the postprandial insulin concentration. In addition, the concentrations of other betaines, e.g., glycine betaine and proline betaine, correlated with glucose and insulin concentrations at the end of the intervention. Conclusions: Novel betainized compounds in humans are associated with diets rich in whole grains, and they improve insulin resistance and insulin secretion. These results suggest that these novel compounds may contribute to the beneficial effects of whole grain-rich diets. The studies were registered at clinicaltrials.gov as NCT00945854 (Naples) and NCT00573781 (Kuopio). [ABSTRACT FROM AUTHOR]

Mast cells are tissue-resident cells of the innate immunity, implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). They are present in synovia and their activation has been linked to the potentiation of inflammation in the course of RA. However, recent investigations questioned the role of mast cells in arthritis. In particular, animal models generated conflicting results, so that many of their pro-inflammatory, i.e. pro-arthritogenic functions, even though supported by robust experimental evidence, have been labelled as redundant. At the same time, a growing body of evidence suggests that mast cells can act as tunable immunomodulatory cells. These characteristics, not yet fully understood in the context of RA, could partially explain the inconsistent results obtained with experimental models, which do not account for the pro- and anti-inflammatory functions exerted in more chronic heterogeneous conditions such as RA. Here we present an overview of the current knowledge on mast cell involvement in RA, including the intriguing hypothesis of mast cells acting as subtle immunomodulatory cells and the emerging concept of synovial mast cells as potential biomarkers for patient stratification. [ABSTRACT FROM AUTHOR]

Background and Aims: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown.Methods and Results: As many as 66 obese (BMI 26-40 kg/m2) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049).Conclusion: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. [ABSTRACT FROM AUTHOR]

Aim: Evidence showed that LDL-cholesterol lowering is associated with a significant cardiovascular risk reduction. The initial therapeutic approach to hypercholesterolemia includes dietary modifications but the compliance to recommendations is often inadequate. Some dietary components with potential cholesterol-lowering activity are present in small amounts in food. Therefore, in recent years the use of "nutraceuticals" (i.e., nutrients and/or bioactive compounds with potential beneficial effects on human health) has become widespread. Such substances may be added to foods and beverages, or taken as dietary supplements (liquid preparations, tablets, capsules). In the present manuscript, the cholesterol-lowering activity of some nutraceuticals (i.e. fiber, phytosterols, soy, policosanol, red yeast rice and berberine) will be discussed along with: 1) the level of evidence on the cholesterol-lowering efficacy emerging from clinical trial; 2) the possible side effects associated with their use; 3) the categories of patients who could benefit from their use.Data Synthesis: Based on the current literature, the cholesterol-lowering effect of fiber, phytosterols and red yeast rice is consistent and supported by a good level of evidence. Over berberine, there is sufficient evidence showing significant cholesterol-lowering effects, although the results come from studies carried out almost exclusively in Asian populations. Data on the effects of soy are conflicting and, therefore, the strength of recommendation is quite low. The evidence on policosanol is inconclusive.Conclusion: Although health benefits may arise from the use of nutraceuticals with cholesterol-lowering activity, their use might be also associated with possible risks and pitfalls, some of which are common to all nutraceuticals whereas others are related to specific nutraceuticals. [ABSTRACT FROM AUTHOR]

Studies on metabolism of polyphenols have revealed extensive transformations in the carbon backbone by colonic microbiota; however, the influence of microbial and hepatic transformations on human urinary metabolites has not been explored. Therefore, the aims of this study were (1) to compare the in vitro microbial phenolic metabolite profile of foods and beverages with that excreted in urine of subjects consuming the same foodstuff and (2) to explore the role of liver on postcolonic metabolism of polyphenols by using in vitro hepatic models. A 24-h urinary phenolic metabolite profile was evaluated in 72 subjects participating in an 8-week clinical trial during which they were randomly assigned to diets differing for polyphenol content. Polyphenol-rich foods and beverages used in the clinical trial were subjected to human fecal microbiota in the in vitro colon model. Metabolites from green tea, one of the main components of the polyphenol-rich diet, were incubated with primary hepatocytes to highlight hepatic conversion of polyphenols. The analyses were performed using targeted gas chromatography with mass spectrometer (GCxGC-TOFMS:colon model; GC-MS: urine and hepatocytes). A significant correlation was found between urinary and colonic metabolites with C1-C3 side chain (P=.040). However, considerably higher amounts of hippuric acid, 3-hydroxybenzoic acid and ferulic acid were detected in urine than in the colon model. The hepatic conversion showed additional amounts of these metabolites complementing the gap between in vitro colon model and the in vivo urinary excretion. Therefore, combining in vitro colon and hepatic models may better elucidate the metabolism of polyphenols from dietary exposure to urinary metabolites. [ABSTRACT FROM AUTHOR]

Background and Aims: The role of the different factors associated with fatty liver is still poorly defined. We evaluated the relationships between liver fat content (LF) and metabolic, inflammatory and nutritional factors in a homogeneous cohort of individuals at high cardio-metabolic risk.Methods and Results: In 70 individuals with high waist circumference and at least one more criterion for metabolic syndrome enrolled in a nutritional intervention study, LF was evaluated at baseline by hepatic/renal echo intensity ratio (H/R), together with dietary habits (7-day dietary record), insulin sensitivity and β-cell function (fasting and OGTT-derived indices), fasting and postprandial plasma GLP-1 and lipoproteins, and plasma inflammatory markers. H/R correlated positively with fasting and OGTT plasma glucose and insulin concentrations, HOMA-IR and β-cell function, and IL-4, IL-17, IFN-γ, TNF-α, FGF and GCSF plasma concentrations (p < 0.05 for all), and negatively with insulin sensitivity (OGIS), dietary, polyphenols and fiber (p < 0.05 for all). By multiple stepwise regression analysis, the best predictors of H/R were OGIS (β = -0.352 p = 0.001), postprandial GLP-1 (β = -0.344; p = 0.001), HDL-cholesterol (β = -0.323; p = 0.002) and IFN-γ (β = 0.205; p = 0.036).Conclusion: A comprehensive evaluation of factors associated with liver fat, in a homogeneous population at high cardio-metabolic risk, indicated a pathogenic combination of the same pathways underlying the atherosclerotic process, namely whole body insulin sensitivity and inflammation. The higher predictive value of postprandial variables suggests that liver fat is essentially a postprandial phenomenon, with a relevant role possibly played by GLP-1.Registration Number For Clinical Trials: NCT01154478. [ABSTRACT FROM AUTHOR]

Background and Aim: To evaluate the combined contribution of UCP3-55CT and PPARγ2 Pro12Ala polymorphisms as correlates of BMI, energy expenditure (REE) and substrate oxidation in people with type 2 diabetes.Methods and Results: Two independent population with type 2 diabetes were studied: population A, n = 272; population B, n = 269. Based on both UCP3 and PPARγ2 genotypes three groups were created. Carriers of the PPARγ2 Pro12Ala in combination with the CC genotype of UCP3 (ProAla/CC, group 1); carriers of only one of these genotypes (either CC/ProPro or CT-TT/ProAla, group 2); people with neither variants (CT-TT/ProPro, group 3). In both populations BMI (kg/m(2)) was highest in group 1, intermediate in group 2 and lowest in group 3, independent of energy intake (i.e 35.3 ± 6.7 vs 33.4 ± 5.4 vs 31.8 ± 3, p < 0.02, population A; 32.4 ± 4.2 vs 31.7 ± 3.8 vs 30.1 ± 2.7; p < 0.03, population B). People with the ProAla/CC genotype (group 1) showed similar REE, but lower lipid oxidation (10.9 vs 13.9 g/kg fat free mass/day; p = 0.04) and higher carbohydrate oxidation (23.6 vs 15.6 g/kg fat free mass/day; p = 0.02) than carriers of other genotypes.Conclusions: The combination of UCP3-55 CC and PPARγ2 Pro12Ala genotypes is associated with significantly higher BMI than other PPARγ2-UCP3 genotype combinations, partly due to a reduced ability in lipids oxidation. The relative importance of these mechanism(s) may be different in non diabetic people. [ABSTRACT FROM AUTHOR]

Background: Epidemiology associates whole-grain (WG) consumption with several health benefits. Mounting evidence suggests that WG wheat polyphenols play a role in mechanisms underlying health benefits. Objective: The objective was to assess circulating concentration, excretion, and the physiologic role of WG wheat polyphenols in subjects with suboptimal dietary and lifestyle behaviors. Design: A placebo-controlled, parallel-group randomized trial with 80 healthy overweight/obese subjects with low intake of fruits and vegetables and sedentary lifestyle was performed. Participants replaced precise portions of refined wheat (RW) with a fixed amount of selected WG wheat or RW products for 8 wk. At baseline and every 4 wk, blood, urine, feces, and anthropometric and body composition measures were collected. Profiles of phenolic acids in biological samples, plasma markers of metabolic disease and inflammation, and fecal microbiota composition were assessed. Results: WG consumption for 4-8 wk determined a 4-fold increase of serum dihydroferulic acid (DHFA) and a 2-fold increase of fecal ferulic acid (FA) compared with RW consumption (no changes). Similarly, urinary FA at 8 wk doubled the baseline concentration only in WG subjects. Concomitant reduction of plasma tumor necrosis factor-α (TNF-α) after 8 wk and increased interleukin (IL)-10 only after 4 wk with WG compared with RW (P = 0.04) were observed. No significant change in plasma metabolic disease markers over the study period was observed, but a trend toward lower plasma plasminogen activator inhibitor 1 with higher excretion of FA and DHFA in the WG group was found. Fecal FA was associated with baseline low Bifidobacteriales and Bacteroidetes abundances, whereas after WG consumption, it correlated with increased Bacteroidetes and Firmicutes but reduced Clostridium. TNF-α reduction correlated with increased Bacteroides and Lactobacillus. No effect of dietary interventions on anthropometry and body composition was found. Conclusions: WG wheat consumption significantly increased excreted FA and circulating DHFA. Bacterial communities influenced fecal FA and were modified by WG wheat consumption. This trial was registered at clinicaltrials.gov as NCT01293175. [ABSTRACT FROM AUTHOR]

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional dietadopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health. [ABSTRACT FROM AUTHOR]

Clinical trials are needed to confirm the association between polyphenol consumption and lower incidence of chronic diseases observed in epidemiological studies. However, a reliable evaluation of polyphenol intake is complicated. An 8-week randomized controlled trial (78 subjects) was performed using two isoenergetic diets differing only for polyphenol contents. Then, urinary phenolic metabolite profiles were analysed using gas-chromatography with mass detection. Phenolic metabolites detected in 24-h-urine were hydroxylated phenolic acids with C1-C3 side chain in the group consuming polyphenol-rich diet. The intake of polyphenol-rich foods increases the excretion of phenolic metabolites in urine providing a profile, which may serve as compliance biomarker of polyphenol-rich diet. [ABSTRACT FROM AUTHOR]

Background and aim Until recently, very few intervention studies have investigated the effects of whole-grain cereals on postprandial glucose, insulin and lipid metabolism, and the existing studies have provided mixed results. The objective of this study was to evaluate the effects of a 12-week intervention with either a whole-grain-based or a refined cereal-based diet on postprandial glucose, insulin and lipid metabolism in individuals with metabolic syndrome. Methods and results Sixty-one men and women age range 40-65 years, with the metabolic syndrome were recruited to participate in this study using a parallel group design. After a 4-week run-in period, participants were randomly assigned to a 12-week diet based on whole-grain products (whole-grain group) or refined cereal products (control group). Blood samples were taken at the beginning and end of the intervention, both fasting and 3 h after a lunch, to measure biochemical parameters. Generalized linear model (GLM) was used for between-group comparisons. Overall, 26 participants in the control group and 28 in the whole-grain group completed the dietary intervention. Drop-outs (five in the control and two in the whole-grain group) did not affect randomization. After 12 weeks, postprandial insulin and triglyceride responses (evaluated as average change 2 and 3 h after the meal, respectively) decreased by 29% and 43%, respectively, in the whole-grain group compared to the run-in period. Postprandial insulin and triglyceride responses were significantly lower at the end of the intervention in the whole-grain group compared to the control group (p = 0.04 and p = 0.05; respectively) whereas there was no change in postprandial response of glucose and other parameters evaluated. Conclusions A twelve week whole-grain cereal-based diet, compared to refined cereals, reduced postprandial insulin and triglycerides responses. This finding may have implications for type 2 diabetes risk and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: The postprandial triglyceride-rich lipoprotein (TRL) concentration is a recognized independent cardiovascular disease risk factor. Diet is the natural approach for these postprandial alterations. Dietary polyphenols and long chain n23 polyunsaturated fatty acids (LCn3s) are associated with a lower cardiovascular disease risk. Objective: This randomized controlled study evaluated, in persons with a high risk of cardiovascular disease, the effects of diets naturally rich in polyphenols and/or marine LCn3s on plasma TRLs and urinary 8-isoprostane concentrations, a biomarker of oxidative stress. Design: According to a 2 × 2 factorial design, 86 overweight/obese individuals with a large waist circumference and any other component of the metabolic syndrome were randomly assigned to an isoenergetic diet 1) poor in LCn3s and polyphenols, 2) rich in LCn3s, 3) rich in polyphenols, or 4) rich in LCn3s and polyphenols. The diets were similar in all other components. Before and after the 8-wk intervention, fasting and postmeal TRLs and 8-isoprostane concentrations in 24-h urine samples were measured. Results: Dietary adherence was good in all participants. Polyphenols significantly reduced fasting triglyceride concentrations (2-factor ANOVA) in plasma (P = 0.023) and large very-low-density lipoproteins (VLDLs) (P = 0.016) and postprandial triglyceride total area under the curve in plasma (P = 0.041) and large VLDLs (P = 0.004). LCn3s reduced postprandial chylomicron cholesterol and VLDL apolipoprotein B-48. The concentrations of urinary 8-isoprostane decreased significantly with the polyphenol-rich diets. Lipoprotein changes induced by the intervention significantly correlated with changes in 8-isoprostane. Conclusions: Diets naturally rich in polyphenols positively influence fasting and postprandial TRLs and reduce oxidative stress. Marine LCn3s reduce TRLs of exogenous origin. Through their effects on postprandial lipemia and oxidative stress, polyphenols may favorably affect cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT00781365. [ABSTRACT FROM AUTHOR]

Abstract: The Look AHEAD trial, evaluating the effects of weight loss on cardiovascular (CV) morbidity and mortality in overweight/obese people with type 2 diabetes (T2D), was interrupted after a median 9.5-year follow-up because the incidence of CV events was not different between the Intensive Lifestyle Intervention (ILI) and the control groups, and unlikely to statistically change thereafter. This made health providers and patients wondering about clinical value of diet and physical exercise in diabetic patients. Many factors may have made difficult to ascertain benefits of lifestyle intervention, besides the lower than predicted CV event rates. Among others, LDL-cholesterol was lowered more, with a higher use of statins, in the control group. Anyhow, ILI significantly improved numerous health conditions, including quality of life, CV risk factors and blood glucose control, with more diabetes remissions and less use of insulin. The intervention aimed at weight loss by reducing fat calories, and using meal replacements and, eventually, orlistat, likely underemphasizing dietary composition. There is suggestive evidence, in fact, that qualitative changes in dietary composition aiming at higher consumption of foods rich in fiber and with a high vegetable/animal fat ratio favorably influence CV risk in T2D patients. In conclusion, the Look AHEAD showed substantial health benefits of lifestyle modifications. Prevention of CV events may need higher attention to dietary composition, contributing to stricter control of CV risk factors. As a better health-related quality of life in people with diabetes is an important driver of our clinical decisions, efforts on early implementation of behavioral changes through a multifactorial approach are strongly justified. [Copyright &y& Elsevier]

Summary: Background & aims: Intervention studies investigating the effects of wholegrain intake on glucose and insulin metabolism have provided conflicting results. Aim of this study was the evaluation of glucose and insulin metabolism in response to long-term consumption of rye and whole wheat compared with a diet containing the same amount of refined cereal foods, in individuals with metabolic syndrome from two European locations (Kuopio-Finland/Naples-Italy). Methods: 146 individuals of both genders, age range 40–65 years with metabolic syndrome, were recruited to this study with parallel groups. After a 2–4 week run-in period, participants were assigned to a diet based on wholegrain (wholegrain group) or on refined cereal products (control group), each one for a duration of 12 weeks. Peripheral insulin sensitivity, assessed by FSIGT, lipids and inflammatory markers were measured before and at the end of intervention. Results: 61 participants in the control group and 62 in the wholegrain group completed the dietary intervention. Compliance to the two diets was good. At the end of the intervention, insulin sensitivity indices and secretion (SI, QUICKI, DI, dAIRG) and lipids and inflammatory markers did not change significantly in the wholegrain and control groups as compared with baseline and no differences between the two groups were observed. Conclusions: Wholegrain cereal foods consumption compared with refined cereals for 12 weeks did not affect peripheral insulin sensitivity. The study was registered with ClinicalTrials.gov identifier NCT00945854. [Copyright &y& Elsevier]

Abstract: Background and aims: The study explores the degree of control of hyperglycaemia and cardiovascular (CV) disease risk factors in men and women with type 2 diabetes and the impact thereon of obesity, central adiposity, age and use of medications. Methods and results: A cross-sectional survey was conducted at 10 hospital-based outpatients diabetes clinics. 1297 men and 1168 women with no previous CV events were studied. Women were slightly (only one year) older and more obese than men: average BMI was respectively 30.7 ± 5.7 vs 28.6 ± 4.1 kg/m2 (p < 0.001), and prevalence of abdominal obesity was 86% vs 44% (p < 0.001). Women smoked less, but had higher HbA1c, LDL cholesterol, non-HDL cholesterol, systolic blood pressure and serum fibrinogen than men. Accordingly optimal targets for HbA1c (<7%), LDL cholesterol (<100 mg/dL), HDL cholesterol (>40 for men, >50 for women, mg/dL), and systolic blood pressure (<130 mmHg) were less frequently achieved by women than men (respectively 33.8% vs 40.2%; 14.6% vs 19.2%; 34.1% vs 44.5%; 68.8% vs 72%; p < 0.05 for all). Findings were confirmed after stratification for waist circumference (< or ≥ 88 cm for women; < or ≥ 102 cm for men), BMI (< or ≥ 25 kg/m2) or age (< or ≥ 65 years). As for treatment, women were more likely than men to take insulin, alone or in combination with oral hypoglycaemic drugs, to be under anti-hypertensive treatment, whereas the use of lipid lowering drugs was similar in men and women. Conclusions: Control of hyperglycaemia and major CVD risk factors is less satisfactory in women than men. The gender disparities are not fully explained by the higher prevalence of total and central obesity in women; or by a less intensive medical management in women. [Copyright &y& Elsevier]

Abstract: Background and aims: Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovascular risk factors. A formal comparison of these two therapies in terms of cardiovascular morbidity and mortality is lacking. The TOSCA.IT study was designed to explore the effects of adding pioglitazone or a sulfonylurea on cardiovascular events in type 2 diabetic patients inadequately controlled with metformin. Methods: Multicentre, randomized, open label, parallel group trial of 48 month duration. Type 2 diabetic subjects, 50–75 years, BMI 20–45 Kg/m2, on secondary failure to metformin monotherapy will be randomized to add-on a sulfonylurea or pioglitazone. The primary efficacy outcome is a composite endpoint of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned coronary revascularization. Principal secondary outcome is a composite ischemic endpoint of sudden death, fatal and non-fatal myocardial infarction and stroke, endovascular or surgical intervention on the coronary, leg or carotid arteries, major amputations. Side effects, quality of life and economic costs will also be evaluated. Efficacy, safety, tolerability, and study conduct will be monitored by an independent Data Safety Monitoring Board. End points will be adjudicated by an independent external committee. Conclusions: TOSCA.IT is the first on-going study investigating the head-to-head comparison of adding a sulfonylurea or pioglitazone to existing metformin treatment in terms of hard cardiovascular outcomes. Registration: Clinicaltrials.gov ID NCT00700856. [Copyright &y& Elsevier]

Background: Few studies have compared lipoprotein composition with dietary intake. Objective: The lipoprotein subfraction profile was evaluated in relation to diet in Alaska Eskimos at high cardiovascular risk but with a low frequency of hyperlipidemia and high intake of n-3 (omega- 3) fatty acids. Design: A population-based sample (n = 1214) from the Norton Sound Region of Alaska underwent a physical examination and blood sampling. Analyses were from 977 individuals who did not have diabetes or use lipid-lowering medications and had complete dietary information (food-frequency questionnaire) and a lipoprotein subfraction profile (nuclear magnetic resonance spectroscopy). Results: After adjustment for age, BMI, total energy intake, and percentage of energy from fat, the intake of n-3 fatty acids was significantly associated with fewer large VLDLs (P = 0.022 in women, P = 0.064 in men), a smaller VLDL size (P = 0.018 and P = 0.036), more large HDLs (P = 0.179 and P = 0.021), and a larger HDL size (P = 0.004 and P = 0.001). After adjustment for carbohydrate and sugar intakes, large VLDLs (P = 0.042 and 0.018) and VLDL size (P = 0.011 and 0.025) remained negatively associated with n-3 fatty acid intake in women and men, and large HDLs (P = 0.067 and 0.005) and HDL size (P = 0.001 in both) remained positively associated with n-3 fatty acid intake in women and men. In addition, large LDLs (P = 0.040 and P = 0.025) were positively associated in both sexes, and LDL size (P = 0.006) showed a positive association in women. There were no significant relations with total LDL particles in either model. Conclusions: Dietary n-3 fatty acids, independent of the reciprocal changes in carbohydrate and sugar intakes, are associated with an overall favorable lipoprotein profile in terms of cardiovascular risk. Because there are no relations with total LDL particles, the benefit may be related to cardiovascular processes other than atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract: The screening and best treatment for coronary heart disease in diabetic patients is still a matter of debate. For this reason the main Italian scientific societies dealing with diabetes and cardiovascular diseases have tried to finalize a document providing shared recommendations based on the available evidence on : 1) how and who to screen for coronary heart disease, 2) methodologies for the characterization of existing coronary heart disease 3) evaluation of the optimal treatment of cardiovascular risk factors and 4) appropriate revascularization procedures. For each of these points, the levels of evidence and strength of recommendations used in the Italian Standard of Care were adopted. [Copyright &y& Elsevier]

Abstract: Women with diabetes have a high risk of cardiovascular disease that, almost completely eliminates the gender difference in cardiovascular morbidity and mortality between non-diabetic men and women. In this chapter we have reviewed data showing that cardiovascular risk factors are more common, more likely to cluster, or more severe in diabetic women than men; this may be due to biological or behavioural factors. Disparities in accessibility, quality and, possibly, effectiveness of care further disadvantage diabetic women. Based on available data it can be concluded that a large number of CVD deaths are preventable in diabetic women; therefore special attention should be paid to risk factors detection and correction, as well as timely CHD diagnosis and treatment in diabetic women. To meet these needs gender specific guidelines and implementation measures may be in order. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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±7.6years, BMI 27.4±3.0kg/m2 (mean±SD), participated in a randomized sequential crossover study. After 2weeks 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. 9.8g/day). After the two treatment periods (each lasting 3weeks) 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 240min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (−4.3%; p <0.03) and LDL (−4.9%; p <0.04) cholesterol levels were lower than after the refined wheat diet at fasting. Conclusions: Consumption of wholemeal wheat foods for 3weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism, antioxidant status and sub-clinical inflammation markers. [Copyright &y& Elsevier]

Abstract: The aim of this study was to determine the diagnostic performance of ultrasound (US) in the quantitative assessment of steatosis by comparison with proton magnetic resonance spectroscopy (1H-MRS) as a reference standard. Three liver echo-intensity indices were derived: US hepatic mean gray level, hepatic-renal echo-intensity ratio (H/R), and hepatic-portal blood echo-intensity ratio. The 1H-MRS degree of steatosis was determined as percentage fat by wet weight. Regression equations were used to estimate quantitatively hepatic fat content. The hepatic fat content by 1H-MRS analysis ranged from 0.10% to 28.9% (median value, 4.8%). Ultrasound H/R was correlated with the degree of steatosis on 1H-MRS (R 2= 0.92; P < .0001), whereas no correlation with 1H-MRS was found for hepatic mean gray level and hepatic-portal blood echo-intensity ratio. A receiver operating characteristic curve identified the H/R of 2.2 as the best cutoff point for the prediction of 1H-MRS of at least 5%, yielding measures of sensitivity and specificity of 100% and 95%, respectively. In this pilot study, US H/R exhibits high sensitivity and specificity for detecting liver fatty changes. Our results indicate that quantitative evaluation of hepatic fat content can be performed using US H/R and could therefore be a valuable analytic tool in clinical investigation. [Copyright &y& Elsevier]

Abstract: Background: Metabolic syndrome (MS) is associated with dyslipidemia, and insulin resistance (IR) may be a main determinant of this dyslipidemia. Objective: To determine how lipoprotein particle concentration and size are related to MS and IR in a population-based sample of Alaska Eskimos. Design: Participants underwent a physical exam, personal interview, collection of biological specimens, and diagnostic tests. Setting: This study was conducted in the Norton Sound region of Alaska. Participants: One thousand one hundred fifty-eight Inupiat Eskimo adults (women=653, men=505). Main outcome measures: Lipoprotein particle profile was evaluated by nuclear magnetic resonance (NMR) and related to presence of MS and level of IR. Results: Participants with MS had (a) significantly higher concentrations of all VLDLs and a larger VLDL size (women, p =0.007; men, p =0.0001); (b) higher concentrations of small LDL (women, p <0.0001; men, p =0.09) and lower concentrations of large LDL (women, p <0.0001), leading to a smaller overall LDL size (women, p <0.0001; men, p <0.05); (c) significantly lower concentrations of large HDL (both genders, p <0.0001) and an increase in intermediate (women, p <0.05) and small HDL (women, p <0.0001; men, p <0.004). Lipoprotein profile with increasing HOMA-IR resembled that of individuals with MS. Conclusions: In this population MS is characterized by lipoprotein distribution and size abnormalities independent of obesity, age, and other cardiovascular risk factors, including lipid concentration. IR seems the major determinant. [Copyright &y& Elsevier]

Abstract: Background and aims: Postprandial lipoprotein abnormalities in type 2 diabetes are associated with insulin resistance. The role of other diabetes-related factors is still not clear. The aim of this study is to differentiate the effects of whole-body insulin resistance, obesity, and type 2 diabetes on postprandial dyslipidaemia and lipoprotein lipase (LPL) in adipose tissue. Methods and results: Ten subjects with obesity and diabetes (OD), 11 with obesity alone (O), and 11 normal-weight controls (C) – males, aged 26–59 years, with fasting normo-triglyceridaemia underwent measurements of cholesterol, triglycerides, apo B-48 and apo B-100 concentrations in plasma lipoproteins separated by density gradient ultracentrifugation before and after a fat-rich meal. Fasting and postprandial (6h) LPL activity was determined in abdominal subcutaneous adipose tissue biopsy samples. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp. OD and O subjects had similar degrees of adiposity (BMI, waist circumference, fat mass) and insulin resistance (insulin stimulated glucose disposal and M/I). They also showed a similarly higher postprandial increase in large VLDL lipids (triglyceride incremental AUC 188±28 and 135±22mg/dl·6h) than C (87±13mg/dl·6h, M ±SEM, p <0.05). OD had an increased chylomicron response compared to O (triglyceride incremental AUC 132±23 vs. 75±14mg/dl·6h, p <0.05). OD had significantly lower fasting and postprandial adipose tissue heparin-releasable LPL activity than O and C. Conclusions: In insulin-resistant conditions of obesity, with and without diabetes, large VLDL are increased after a fat-rich meal. In addition, diabetic patients compared to obese subjects have an increased postprandial chylomicron response and a reduced adipose tissue LPL activity. [Copyright &y& Elsevier]

Summary: Background: The effects of different dietary fatty acids on postprandial lipid metabolism in type 2 diabetic patients are still debated. Aim: To evaluate the effects of monounsaturated (MUFA) vs. saturated fat (SAFA)-rich diets on postprandial lipemia and adipose tissue lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in type 2 diabetes. Materials and methods: Eleven type 2 diabetic patients followed, in random order, a diet rich in MUFA (SAFA 8%, MUFA 23%) and another rich in SAFA (SAFA 17%, MUFA 15%) for a period of 3 weeks each. At the end of the two diets, a standard fat-rich meal was administered and subcutaneous fat biopsies were performed at fasting and 6h after the test meal. Results: Neither diet induced significant changes in meal lipid tolerance, except for a faster (at 2h) increase in chylomicron triglycerides and a significant decrease in small VLDL triglyceride incremental area after the MUFA diet (−13.6±4.7mg/dl*6h vs. −2.2±3.7mg/dl*6h, p<0.005) (M±SEM). LPL and HSL activities were significantly increased after the MUFA diet. Conclusions: A MUFA-rich diet reduces postprandial small VLDL triglycerides in type 2 diabetic patients compared to a SAFA-rich diet, and modifies lipolytic enzymes in adipose tissue. [Copyright &y& Elsevier]

Abstract: Background and aims: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity. Methods and results: Altogether 151 healthy subjects (age 49±8years, BMI 26.5±3.0kg/m2) were randomly assigned for 3months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P =0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P =0.007 among three genotypes). The rare -250A allele was related to low HL activity (P <0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes. Conclusion: The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype. [Copyright &y& Elsevier]

Abstract: Aim: To evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity, insulin secretion, β-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat, also in relation to their habitual dietary intake of n-6 and n-3 fatty acid. Methods and results: One hundred and sixty-two healthy individuals were randomly assigned to follow either one of two isoenergetic diets for 3months, one rich in monounsaturated fats and the other rich in saturated fats. Within each group there was a second randomisation to fish oil (n-3 fatty acids 3.6g/day) or placebo. At the beginning and at the end of the treatment periods insulin sensitivity (SI), first phase insulin response (FPIR) and glucose tolerance (KG-value) were evaluated by the intravenous glucose tolerance test (IVGTT). Fish oil did not have any effect on SI, FPIR, KG-value and disposition index in either diet. Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline, there was no change in SI (Δ SI 0.42±0.34 on fish oil vs 0.14±0.23 on placebo for those with n-6/n-3 <4.85; −1.03±0.47 on fish oil vs −0.27±0.32 on placebo for those with n-6/n-3 >4.85) (M±SE), FPIR (Δ FPIR 135.9±78.9 vs 157.2±157.5pmol/L; 38.8±181.7 vs 357.1±181.7pmol/L), KG-value (Δ KG 0.14±0.15 vs 0.12±0.11; −0.32±0.16 vs 0.15±0.15) or disposition index (Δ disposition index 1465.4±830.4 vs 953.8±690.0; −1641.6±1034.3 vs 446.6±905.1). Considering the 75th percentile of n-6/n-3 ratio (5.82) the results on insulin sensitivity, insulin secretion and disposition index were confirmed, while, in this more extreme situation, n-3 fatty acid supplementation induced a significant deterioration of KG-value (p =0.02). Conclusions: In healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, β-cell function or glucose tolerance. The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account. [Copyright &y& Elsevier]

(n-3) Fatty acids are unsaturated and are therefore easily subject to oxidization; however, they have several beneficial health effects, which include protection against cardiovascular diseases. The aim of this study was to investigate whether (n-3) fatty acids, with a controlled fat quality in the background diet, affect nonenzymatic and enzymatic lipid peroxidation and antioxidant status in humans. A total of 162 men and women in a multicenter study (The KANWU study) were randomly assigned to a diet containing a high proportion of saturated fatty acids or monounsaturated fatty acids (MUFA) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish-oil capsules [3.6 g (n-3) fatty acids/d] or placebo. Biomarkers of nonenzymatic and enzymatic lipid peroxidation in vivo were determined by measuring 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) and prostaglandin F(2alpha) (PGF(2alpha)) concentrations in plasma at baseline and after 3 mo. Antioxidant status was determined by measuring plasma antioxidant capacity with an enhanced chemiluminescence assay. The plasma 8-iso-PGF(2alpha) concentration was significantly decreased after 3 mo of supplementation with (n-3) fatty acids (P = 0.015), whereas the PGF(2alpha) concentration was not affected. The antioxidant status was not affected by supplementation of (n-3) fatty acids, but was improved by the background diet with a high proportion of MUFA. We conclude that supplementation with (n-3) fatty acids decreases nonenzymatic free radical-catalyzed isoprostane formation, but does not affect cyclooxygenase-mediated prostaglandin formation. [ABSTRACT FROM AUTHOR]