Metabolite Changes After Metabolic Surgery - Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels.

Aims: To test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery. Materials and Methods: This observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days). Results: Twelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels. Conclusions: Our study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement.

Insulin sensitivity depends on the route of glucose administration.

AIMS/HYPOTHESIS: The small intestine plays an important role in hepatic and whole-body insulin sensitivity, as shown by bariatric surgery. Our goal was to study whether routes and dose of glucose administration have an acute impact on insulin sensitivity. The primary endpoint of this proof-of-concept study was the difference in insulin-mediated metabolic clearance rate (MCR/I) of glucose between the oral and intravenous routes of glucose administration. Secondary endpoints were differences in insulin effect on proteolysis, ketogenesis, lipolysis and glucagon levels. METHODS: In this parallel cohort study, we administered multiple oral glucose loads to 23 participants (aged between 18 and 65 years) with morbid obesity and with normal or impaired glucose tolerance or type 2 diabetes. In a different session, we administered isoglycaemic intravenous glucose infusions (IGIVI) to match the plasma glucose levels observed during the oral challenges. Glucose rate of appearance (Ra) and disappearance (Rd) and endogenous glucose production (EGP) were calculated by infusing [6,6-2H2]glucose with or without oral [U-13C6]glucose. Plasma small polar metabolites were measured by gas chromatography and time-of-flight mass spectrometry. Lipids were measured by ultra-HPLC and quadrupole mass spectrometry. Glucagon-like peptide-1, insulin, C-peptide and glucagon were also measured. Participants, caregivers, people doing measurements or examinations, and people assessing the outcomes were unblinded to group assignment. RESULTS: Glucose MCR/I was significantly higher during IGIVI than during oral glucose administration, independently of glycaemic status (12 ± 6 for IGIVI vs 7.4 ± 3 ml min-1 kg-1 per nmol/l for oral, p< 0.001 from paired t test). Insulin secretion was higher during oral administration than during IGIVI (p< 0.001). The disposition index was significantly lower during the oral procedure: 4260 ± 1820 vs 5000 ± 2360 (ml min-1 kg-1 (nmol/l)-1 pmol/min; p = 0.005). Insulin clearance was significantly higher when glucose was infused rather than ingested (2.53 ± 0.82 vs 2.16 ± 0.49 l/min in intravenous and oral procedure, respectively, p = 0.006). The efficacy of insulin in inhibiting lipolysis and proteolysis was decreased after oral glucose loads. A heat map diagram showed a different pattern for the metabolites between the two routes of glucose administration. CONCLUSIONS/INTERPRETATION: Our study shows that insulin sensitivity depends on the route of glucose administration, the oral route leading to increased insulin secretion and compensatory insulin resistance compared with the intravenous route. The efficacy of insulin in blocking lipolysis and protein breakdown is lower after oral glucose loads vs the intravenous route. Our findings suggest that, while the glucose-mediated incretin release is followed by an increase in insulin release, the effect of the released insulin is limited by an increase in insulin resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT03223129. Graphical abstract.

Lipidome as a predictive tool in progression to type 2 diabetes in Finnish men.

BACKGROUND: There is a need for early markers to track and predict the development of type 2 diabetes mellitus (T2DM) from the state of normal glucose tolerance through prediabetes. In this study we tested whether the plasma molecular lipidome has biomarker potential to predicting the onset of T2DM. METHODS: We applied global lipidomic profiling on plasma samples from well-phenotyped men (107 cases, 216 controls) participating in the longitudinal METSIM study at baseline and at five-year follow-up. To validate the lipid markers, an additional study with a representative sample of adult male population (n=631) was also conducted. A total of 277 plasma lipids were analyzed using the lipidomics platform based on ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. Lipids with the highest predictive power for the development of T2DM were computationally selected, validated and compared to standard risk models without lipids. RESULTS: A persistent lipid signature with higher levels of triacylglycerols and diacyl-phospholipids as well as lower levels of alkylacyl phosphatidylcholines was observed in progressors to T2DM. Lysophosphatidylcholine acyl C18:2 (LysoPC(18:2)), phosphatidylcholines PC(32:1), PC(34:2e) and PC(36:1), and triacylglycerol TG(17:1/18:1/18:2) were selected to the full model that included metabolic risk factors and FINDRISC variables. When further adjusting for BMI and age, these lipids had respective odds ratios of 0.32, 2.4, 0.50, 2.2 and 0.31 (all p<0.05) for progression to T2DM. The independently-validated predictive power improved in all pairwise comparisons between the lipid model and the respective standard risk model without the lipids (integrated discrimination improvement IDI>0; p<0.05). Notably, the lipid models remained predictive of the development of T2DM in the fasting plasma glucose-matched subset of the validation study. CONCLUSION: This study indicates that a lipid signature characteristic of T2DM is present years before the diagnosis and improves prediction of progression to T2DM. Molecular lipid biomarkers were shown to have predictive power also in a high-risk group, where standard risk factors are not helpful at distinguishing progressors from non-progressors.

Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses.

Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases.

Effects of short- and long-term Mediterranean-based dietary treatment on plasma LC-QTOF/MS metabolic profiling of subjects with metabolic syndrome features: The Metabolic Syndrome Reduction in Navarra (RESMENA) randomized controlled trial.

SCOPE: Adherence to the Mediterranean diet has been associated with a reduced risk of metabolic syndrome (MetS). Metabolomics approach may contribute to identify beneficial associations of metabolic changes affected by Mediterranean diet-based interventions with inflammatory and oxidative-stress markers related to the etiology and development of the MetS. METHODS AND RESULTS: Liquid chromatography coupled to quadrupole-time of flight-MS metabolic profiling was applied to plasma from a 6-month randomized intervention with two sequential periods, a 2-month nutritional-learning intervention period, and a 4-month self-control period, with two energy-restricted diets; the RESMENA diet (based on the Mediterranean dietary pattern) and the Control diet (based on the American Heart Association guidelines), in 72 subjects with a high BMI and at least two features of MetS. The major contributing biomarkers of each sequential period were lipids, mainly phospholipids and lysophospholipids. Dependency network analysis showed a different pattern of associations between metabolic changes and clinical variables after 2 and 6 month of intervention, with a highly interconnected network during the nutritional-learning intervention period of the study. CONCLUSION: The 2-month RESMENA diet produced significant changes in the plasma metabolic profile of subjects with MetS features. However, at the end of the 6-month study, most of the associations between metabolic and clinical variables disappeared; suggesting that adherence to healthy dietary habits had declined during the self-control period.

Isoenergetic diets differing in their n-3 fatty acid and polyphenol content reflect different plasma and HDL-fraction lipidomic profiles in subjects at high cardiovascular risk.

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.

Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge.

Postprandial responses to food are complex, involving both genetic and environmental factors. We studied postprandial responses to a Big Mac meal challenge in monozygotic co-twins highly discordant for body weight. This unique design allows assessment of the contribution of obesity, independent of genetic liability. Comprehensive metabolic profiling using 3 analytical platforms was applied to fasting and postprandial serum samples from 16 healthy monozygotic twin pairs discordant for weight (body mass index difference >3 kg/m(2)). Nine concordant monozygotic pairs were examined as control pairs. Fecal samples were analyzed to assess diversity of the major bacterial groups by using 5 different validated bacterial group specific denaturing gradient gel electrophoresis methods. No differences in fecal bacterial diversity were detected when comparing co-twins discordant for weight (ANOVA, P<0.05). We found that within-pair similarity is a dominant factor in the metabolic postprandial response, independent of acquired obesity. Branched chain amino acids were increased in heavier as compared with leaner co-twins in the fasting state, but their levels converged postprandially (paired t tests, FDR q<0.05). We also found that specific bacterial groups were associated with postprandial changes of specific metabolites. Our findings underline important roles of genetic and early life factors in the regulation of postprandial metabolite levels.

A new dietary strategy for long-term treatment of the metabolic syndrome is compared with the American Heart Association (AHA) guidelines: the MEtabolic Syndrome REduction in NAvarra (RESMENA) project.

The long-term effects of dietary strategies designed to combat the metabolic syndrome (MetS) remain unknown. The present study evaluated the effectiveness of a new dietary strategy based on macronutrient distribution, antioxidant capacity and meal frequency (MEtabolic Syndrome REduction in NAvarra (RESMENA) diet) for the treatment of the MetS when compared with the American Heart Association guidelines, used as Control. Subjects with the MetS (fifty-two men and forty-one women, age 49 (se 1) years, BMI 36·11 (se 0·5) kg/m²) were randomly assigned to one of two dietary groups. After a 2-month nutritional-learning intervention period, during which a nutritional assessment was made for the participants every 15 d, a 4-month self-control period began. No significant differences were found between the groups concerning anthropometry, but only the RESMENA group exhibited a significant decrease in body weight ( - 1·7%; P= 0·018), BMI ( - 1·7%; P= 0·019), waist circumference ( - 1·8%; P= 0·021), waist:hip ratio ( - 1·4%; P= 0·035) and android fat mass ( - 6·9%; P= 0·008). The RESMENA group exhibited a significant decrease in alanine aminotransferase and aspartate aminotransferase (AST) concentrations ( - 26·8%; P= 0·008 and - 14·0%; P= 0·018, respectively), while the Control group exhibited a significant increase in glucose (7·9%; P= 0·011), AST (11·3%; P= 0·045) and uric acid (9·0%; P< 0·001) concentrations. LDL-cholesterol (LDL-C) concentrations were increased (Control group: 34·4%; P< 0·001 and RESMENA group: 33·8%; P< 0·001), but interestingly so were the LDL-C:apoB ratio (Control group: 28·7%; P< 0·001, RESMENA group: 17·1%; P= 0·009) and HDL-cholesterol concentrations (Control group: 21·1%; P< 0·001, RESMENA group: 8·7; P= 0·001). Fibre was the dietary component that most contributed to the improvement of anthropometry, while body-weight loss explained changes in some biochemical markers. In conclusion, the RESMENA diet is a good long-term dietary treatment for the MetS.

Nutri-metabolomics: subtle serum metabolic differences in healthy subjects by NMR-based metabolomics after a short-term nutritional intervention with two tomato sauces.

Postgenomics research and development is witnessing novel intersections of omics data intensive technology and applications in health and personalized nutrition. Chief among these is the nascent field of nutri-metabolomics that harnesses metabolomics platforms to discern person-to-person variations in nutritional responses. To this end, differences in the origin and ripening stage of fruits might have a strong impact on their phytochemical composition, and consequently, on their potential nutri-metabolomics effects on health. The objective of the present study was to evaluate the effects of a 4-week cross-over nutritional intervention on the metabolic status of 24 young healthy subjects. The intervention was carried out with two tomato sauces differing in their natural lycopene content, which was achieved by using tomatoes harvested at different times. Blood samples were drawn from each subject before and after each intervention period. Aqueous and lipid extracts from serum samples were analyzed by 1H-NMR metabolic profiling combined with analysis of variance simultaneous component analysis (ASCA) and multilevel simultaneous component analysis (MSCA). These methods allowed the interpretation of the variation induced by the main factors of the study design (sauce treatment and time). The levels of creatine, creatinine, leucine, choline, methionine, and acetate in aqueous extracts were increased after the intervention with the high-lycopene content sauce, while those of ascorbic acid, lactate, pyruvate, isoleucine, alanine were increased after the normal-lycopene content sauce. In conclusion, NMR-based metabolomics of aqueous and lipid extracts allowed the detection of different metabolic changes after the nutritional intervention. This outcome might partly be due to the different ripening state of the fruits used in production of the tomato sauces. The findings presented herein collectively attest to the emergence of the field of nutri-metabolomics as a novel subspecialty of postgenomics integrative biology.

Short-term role of the dietary total antioxidant capacity in two hypocaloric regimes on obese with metabolic syndrome symptoms: the RESMENA randomized controlled trial.

BACKGROUND: Dietary strategies seem to be the most prescribed therapy in order to counteract obesity regarding not only calorie restriction, but also bioactive ingredients and the composition of the consumed foods. Dietary total antioxidant capacity (TAC) is gaining importance in order to assess the quality of the diet. METHODS: Ninety-six obese adults presenting metabolic syndrome (MetS) symptoms completed an 8-week intervention trial to evaluate the effects of a novel dietary program with changes in the nutrient distribution and meal frequency and to compare it with a dietary pattern based on the American Heart Association (AHA) guidelines.Anthropometric and biochemical parameters were assessed at baseline and at the endpoint of the study, in addition to 48-hours food dietary records. RESULTS: Both diets equally (p > 0.05) improved MetS manifestations. Dietary TAC was the component which showed the major influence on body weight (p = 0.034), body mass index (p = 0.026), waist circumference (p = 0.083) and fat mass (p = 0.015) reductions. Transaminases (ALT and AST) levels (p = 0.062 and p = 0.004, respectively) were associated with lower TAC values. CONCLUSION: RESMENA diet was as effective as AHA pattern for reducing MetS features. Dietary TAC was the most contributing factor involved in body weight and obesity related markers reduction. TRIAL REGISTRATION: http://www.clinicaltrials.gov; NCT01087086.

Lipidomics in nutrition and food research.

Lipids are a diverse class of metabolites that play several key roles in the maintenance of human health. Lipidomics, which focuses on the global study of molecular lipids in cells, tissues, and biofluids, has been advancing rapidly over the past decade. Recent developments in MS and computational methods enable the lipid analysis with high throughput, resolution, sensitivity, and ability for structural identification of several hundreds of lipids. In nutrition research, lipidomics can be effectively used to elucidate the interactions between diet, nutrients, and human metabolism. Lipidomics can also be applied to optimize the effects of food processing on the dietary value, and in the evaluation of food-related health effects.

UPLC-QTOF/MS metabolic profiling unveils urinary changes in humans after a whole grain rye versus refined wheat bread intervention.

SCOPE: Non-targeted urine metabolite profiling has not been previously exploited in the field of whole grain (WG) products. WG products, particularly rye, are important elements in a healthy Nordic diet. The aim of this study was to identify novel urinary biomarkers of WG rye bread (RB) intake in a randomised crossover study with RB versus refined wheat bread (WB). METHODS AND RESULTS: UPLC-QTOF/MS metabolite profiling was applied to urine from a 2 × 4 wk crossover intervention with RB versus WB in 20 subjects. Sixteen metabolites were revealed as major contributing biomarkers. The most discriminative metabolite after the cereal intervention was identified as 3-(3,5-dihydroxyphenyl)-1-propanoic acid sulphate, which was excreted to a higher extent after the RB versus WB intervention. Other alkylresorcinol metabolites were identified, as well as enterolactone glucuronide, azelaic acid, 2-aminophenol sulphate and its benzoxazinoid precursor 2,4-dihydroxy-1,4-benzoxazin-3-one. Our study also suggests that nitrogen-containing metabolites are other major markers. However, other methodologies will be needed to elucidate their final structure. CONCLUSION: The present non-targeted metabolite profiling proved to be a useful approach to identify major urine metabolites discriminating RB intake from that of white wheat bread. Once validated these markers could help evaluate compliance to healthy Nordic diets.

Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women--a randomized control trial.

BACKGROUND: Epidemiological studies have consistently shown that whole grain (WG) cereals can protect against the development of chronic diseases, but the underlying mechanism is not fully understood. Among WG products, WG rye is considered even more potent because of its unique discrepancy in postprandial insulin and glucose responses known as the rye factor. In this study, an NMR-based metabolomics approach was applied to study the metabolic effects of WG rye as a tool to determine the beneficial effects of WG rye on human health. METHODS: Thirty-three postmenopausal Finnish women with elevated serum total cholesterol (5.0-8.5 mmol/L) and BMI of 20-33 kg/m² consumed a minimum of 20% of their daily energy intake as high fiber WG rye bread (RB) or refined wheat bread (WB) in a randomized, controlled, crossover design with two 8-wk intervention periods separated by an 8-wk washout period. At the end of each intervention period, fasting serum was collected for NMR-based metabolomics and the analysis of cholesterol fractions. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. RESULTS: The metabolomics analysis of serum showed lower leucine and isoleucine and higher betaine and N,N-dimethylglycine levels after RB than WB intake. To further investigate the metabolic effects of RB, the serum cholesterol fractions were measured. Total- and LDL-cholesterol levels were higher after RB intake than after WB (p<0.05). CONCLUSIONS: This study revealed favorable shifts in branched amino acid and single carbon metabolism and an unfavorable shift in serum cholesterol levels after RB intake in postmenopausal women, which should be considered for evaluating health beneficial effects of rye products.

Oxidative stress and inflammation interactions in human obesity.

Obesity is often characterized by increased oxidative stress and exacerbated inflammatory outcomes accompanying infiltration of immune cells in adipocytes. The oxidative stress machinery and inflammatory signaling are not only interrelated, but their impairment can lead to an inhibition of insulin responses as well as a higher risk of cardiovascular diseases and associated features. Mitochondria, in addition to energy transformation, play a role in apoptosis, cellular proliferation, as well as in the cellular redox state control. Under certain circumstances, protons are able to re-enter the mitochondrial matrix via different uncoupling proteins, disturbing free radical production by mitochondria. Disorders of the mitochondrial electron transport chain, over-generation of reactive oxygen species, and lipoperoxides or alterations in antioxidant defenses have been reported in situations of obesity and type-2 diabetes. On the other hand, obesity has been linked to a low grade pro-inflammatory state, in which impairments in the oxidative stress and antioxidant mechanism could be involved. The current scientific evidence highlights the need of investigating the interplay between oxidative stress and inflammation with obesity/diabetes onset as well as the interactions of such factors either as a cause or consequence of obesity. The signaling mediated by the activation of inflammatory markers or nuclear factor kappa ß and other transcription factors as central regulators of inflammation are key issues to understanding oxidative stress responses in obesity. This review aims at summarizing the main mechanisms and interplay factors between oxidative stress and inflammation in human obesity according to the last 10 years of research in the field.

Postprandial differences in the plasma metabolome of healthy Finnish subjects after intake of a sourdough fermented endosperm rye bread versus white wheat bread.

BACKGROUND: The mechanism behind the lowered postprandial insulin demand observed after rye bread intake compared to wheat bread is unknown. The aim of this study was to use the metabolomics approach to identify potential metabolites related to amino acid metabolism involved in this mechanism. METHODS: A sourdough fermented endosperm rye bread (RB) and a standard white wheat bread (WB) as a reference were served in random order to 16 healthy subjects. Test bread portions contained 50 g available carbohydrate. In vitro hydrolysis of starch and protein were performed for both test breads. Blood samples for measuring glucose and insulin concentrations were drawn over 4 h and gastric emptying rate (GER) was measured. Changes in the plasma metabolome were investigated by applying a comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry metabolomics platform (GC × GC-TOF-MS). RESULTS: Plasma insulin response to RB was lower than to WB at 30 min (P = 0.004), 45 min (P = 0.002) and 60 min (P < 0.001) after bread intake, and plasma glucose response was significantly higher at time point 90 min after RB than WB intake (P = 0.045). The starch hydrolysis rate was higher for RB than WB, contrary to the in vitro protein digestibility. There were no differences in GER between breads. From 255 metabolites identified by the metabolomics platform, 26 showed significant postprandial relative changes after 30 minutes of bread intake (p and q values < 0.05). Among them, there were changes in essential amino acids (phenylalanine, methionine, tyrosine and glutamic acid), metabolites involved in the tricarboxylic acid cycle (alpha-ketoglutaric, pyruvic acid and citric acid) and several organic acids. Interestingly, the levels of two compounds involved in the tryptophan metabolism (picolinic acid, ribitol) significantly changed depending on the different bread intake. CONCLUSIONS: A single meal of a low fibre sourdough rye bread producing low postprandial insulin response brings in several changes in plasma amino acids and their metabolites and some of these might have properties beneficial for health.

Liver proteome changes induced by a short-term high-fat sucrose diet in wistar rats.

BACKGROUND/AIMS: The aim of this study was to gain insight into those proteins that might be involved in the early stages of liver fat accumulation as a consequence of a different fat versus simple sugar dietary intake. METHODS: Forty-five male Wistar rats were randomly distributed into four dietary groups: a starch-rich control diet (CD; n = 10), a high-fat diet (n = 12), a high-sucrose diet (n = 11), and a high-fat sucrose diet (HFSD; n = 12) for 5 weeks. A comparative analysis by 2D-DIGE and LC-ESI-MS/MS was performed to characterize the liver protein expression profiles due to the three obesogenic diets. RESULTS: Ten out of 17 proteins whose expression levels were altered by >1.25-fold were identified. Four proteins (Hspa8, Hspa9, Ca3, and Cat) were differentially expressed after the HFSD period compared to CD. The heat shock proteins (Hspa8 and Hspa9) resulted significantly downregulated in liver from rats fed HFSD versus CD (p < 0.05). The results were confirmed by Western blot. CONCLUSIONS: This descriptive study might be useful for further studies aiming at understanding the mechanisms by which diets rich in both fat and sugar affect the initiation of hepatic steatosis.

Impact of dietary polyphenols on carbohydrate metabolism.

Polyphenols, including flavonoids, phenolic acids, proanthocyanidins and resveratrol, are a large and heterogeneous group of phytochemicals in plant-based foods, such as tea, coffee, wine, cocoa, cereal grains, soy, fruits and berries. Growing evidence indicates that various dietary polyphenols may influence carbohydrate metabolism at many levels. In animal models and a limited number of human studies carried out so far, polyphenols and foods or beverages rich in polyphenols have attenuated postprandial glycemic responses and fasting hyperglycemia, and improved acute insulin secretion and insulin sensitivity. The possible mechanisms include inhibition of carbohydrate digestion and glucose absorption in the intestine, stimulation of insulin secretion from the pancreatic beta-cells, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in the insulin-sensitive tissues, and modulation of intracellular signalling pathways and gene expression. The positive effects of polyphenols on glucose homeostasis observed in a large number of in vitro and animal models are supported by epidemiological evidence on polyphenol-rich diets. To confirm the implications of polyphenol consumption for prevention of insulin resistance, metabolic syndrome and eventually type 2 diabetes, human trials with well-defined diets, controlled study designs and clinically relevant end-points together with holistic approaches e.g., systems biology profiling technologies are needed.

Diet quality of a population sample from coastal north-east Spain evaluated by a Mediterranean adaptation of the diet quality index (DQI).

OBJECTIVE: To assess the adherence to the Mediterranean dietary pattern in the population from a coastal region from north-east Spain and its relationship to diseases, applying the Mediterranean Diet Quality Index (M-DQI) validated by the use of several biomarkers. DESIGN: Cross-sectional nutrition survey. SETTING: Population-based random sample derived from the Catalan Nutrition Survey. SUBJECTS: A total of 621 healthy adults. RESULTS: The Catalan representative sample presented a mean M-DQI score of 6.6 (sd 2.3, median 7, range 0-14). The percentage of adherence to the Mediterranean diet was 53 %; 10 % of subjects showed high adherence to the Mediterranean diet, while only 2 % were categorized as poorest adherence. The plasma fatty acid profile of the Catalan sample progressed with perfect regularity throughout the index ranges. Both EPA and DHA presented a significant correlation to the M-DQI (r = -0.410 for EPA and -0.360 for DHA). A significant increase in palmitic, oleic and alpha-linolenic acids and a significant decrease in stearic, linoleic and arachidonic acids content were also observed. The mean values for the M-DQI according to the clinical characteristics of the Catalan sample were also calculated. CONCLUSIONS: The M-DQI has been demonstrated a suitable tool for assessment of an individual's nutritional status according to the Mediterranean dietary pattern and for clinical purposes. Although the current diet followed in Catalonia seems to agree with the main characteristics of the Mediterranean diet, the promotion of the Mediterranean pattern should be reinforced in the Catalan population, especially among young people.

Identification of foods contributing to the dietary lipid profile of a Mediterranean population.

The identification of the target foods that most affect the fat content of a diet, independently whether or not they contain fat, can be a useful tool in the process of drawing up more effective dietary guidelines with nutritional education strategies more directed at the needs of each population. With this purpose, the contribution analysis designed by Block and colleagues and multiple linear regression models were applied to a representative sample of Catalonia. Olive oil was the food that provided the highest absolute and relative percentage of fat-derived energy intake and cheese the food that provided the highest percentage of saturated fat-derived energy intake. According to the results of the present work, during the last 10 years the consumption of fruits and vegetables in Catalonia has increased, more in women than men. The intake of white fish is significantly higher than the intake of blue fish, which should be increased in both men and women, and red meat is still the first meat source in this population. Special attention should be paid to the increasing sweet cereal consumption, which is a source of invisible fat to the diet.

Moderate consumption of olive oil by healthy European men reduces systolic blood pressure in non-Mediterranean participants.

We evaluated the effects of a moderate consumption of olive oil on lipid profile, BMI, and blood pressure (BP) in a group of 160 healthy men from non-Mediterranean regions [Northern Europe (n = 50; Finland and Denmark) and Central Europe (n = 60; Germany)] and Mediterranean regions [Southern Europe (n = 45; Italy and Spain)]. The study was a randomized, cross-over trial with 3 intervention periods of 3 wk and 2 wash-out periods of 2 wk. At the intervention periods, 3 similar olive oils (25 mL/d), differing only in their phenolic concentration, were administered to the healthy volunteers. Plasma oleic acid levels increased 2-3% (P < 0.05) in men from populations with lower habitual olive oil intakes (Northern and Central Europe). General linear models showed that the administration of the sequence of the 3 olive oils was responsible for a 3% decrease in systolic BP (SBP) (P < 0.05), but not in diastolic BP, in the non-Mediterranean subjects. Multivariate analysis indicated that the lipid profile did not change in either Mediterranean or non-Mediterranean men due to the olive oil intervention. The results of this study suggest that a moderate consumption of olive oil may be used as an effective tool to reduce SBP of healthy men who do not typically consume a Mediterranean diet. However, additional longer trials are necessary for confirmation.