A novel hybrid material with calcium and strontium release capability

The preparation of PDMS–TEOS–CaO hybrid materials by sol–gel techniques has been widely described in previous works. Calcium nitrate is the most common source of calcium used in these preparations. However, to remove possible toxic nitrate by-products a thermal treatment is necessary at temperatures above 500 1C, which leads to the degradation of the polymeric components of the hybrids. Strontium has already shown some promising results in the therapeutic area, being used in cases of osteoporosis and low bone density. In this study a new potential bioactive hybrid material was prepared, by sol–gel techniques, using calcium acetate as a novel calcium source. Also, for the first time, incorporation of strontium in a PDMS–TEOS hybrid system was evaluated. Samples were characterized before and after immersion in Kokubo’s Simulated Body Fluid (SBF) by SEM, EDS, ICP and FT-IR spectroscopy

A 3-year Mediterranean-style dietary intervention may modulate the association between adiponectin gene variants and body weight change

Purpose Adiponectin gene variations have been associated with obesity. There are few interventional studies analyzing this association. The aim of this study was to analyze the effects of a nutritional intervention with Mediterranean-style diet and three (-4034A/C, +45T/G and +276 G/T) adiponectin gene variants on 3-year body weight changes in high cardiovascular risk patients Subjects and methods A total of 737 participants, aged 55-80 at high cardiovascular risk were assigned to a low-fat diet or to a Mediterranean-style diet (MD) groups, one with high intake of virgin olive oil (VOO) and the other with high intake of nuts. Anthropometric parameters were taken at baseline and after 3-year follow-up, and the genotyping of the -4034A/C, +45T/G and +276 G/T polymorphisms was done. Results GG genotype of the +45T/G polymorphism was associated with 3-year higher body weight gain (B=1.399; B=0.043). TT genotype of the +276G/T polymorphism was linked to the highest 3-year body weight gain in men. Both Mediterranean diets appeared to reverse this effect (p for interaction=0.053). Conclusion Adiponectin gene variation appeared to be associated with 3-year body weight changes in a high cardiovascular risk population. This association may be modulated by a nutritional intervention with a Mediterranean-style diet

Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346–CPT1B/CHKB-CPT1B and cg17071192–GNAS/GNASAS, being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genes related to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes

Primary prevention of cardiovascular disease with a Mediterranean diet

BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events

Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study

Background and aim Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions. Methods and results Case-cohort study from the PREDIMED trial involving participants aged 55–80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20–1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12–1.58) for fumarate and 1.47 (95%CI:1.21–1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32–1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention. Conclusion Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk

The Pro12Ala polymorphism of the PPARγ2 gene interacts with a Mediterranean Diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial

Background: The gene variant Pro/Ala (rs1801282) in the PPARγ2 has been associated with lower cardiovascular risk and greater benefit from lifestyle interventions. This polymorphism also seems to be associated with longer lifespan, but no information on telomere length (TL) is available. Our aim was to study the association between the Ala allele and changes in TL in high cardiovascular risk subjects, and the potential interaction with a Mediterranean Diet (MeDiet) pattern. Methods and Results: A total of 521 subjects (55-80 years) participating in the Prevención con Dieta Mediterránea (PREDIMED) randomized trial were genotyped. Changes in TL, measured by quantitative real-time PCR, were assessed over 5 years of a nutritional intervention which promoted adherence to the MeDiet. Interestingly, Ala carriers showed lower telomere shortening after 5 years, compared with the Pro/Pro genotype (P=0.031). This association was modulated by MeDiet since those Ala carriers who reported better conformity to the MeDiet exhibited increased TL (P<0.001). Moreover, a reduction in carbohydrate intake (≤9.5 g/d) resulted in increased TL among Ala carriers. Notably, an apparent gene-diet interaction was found through the observed changes in the MUFA+PUFA/Carbohydrates ratio: as this ratio increased, TL lengthening was detected to a greater extent in the Ala carriers compared with the Pro/Pro subjects (P for interaction <0.001). Conclusions: The Pro12Ala polymorphism is associated with TL homeostasis after 5 years follow-up in subjects at high cardiovascular risk. In addition, a higher adherence to the MeDie

Mediterranean Diet and atherothrombosis biomarkers: a randomized controlled trial

Scope. To assess whether following a Mediterranean diet (MedDiet) improved atherothrombosis biomarkers in high cardiovascular risk individuals. Methods and results. In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, we assessed the 1-year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO; n=120) or nuts (MedDiet-Nuts; n=119) versus a low-fat control diet (n=119). We also studied whether large increments in MedDiet adherence (≥3 score points, relative to compliance decreases) and intake changes in key food items were associated with 1-year differences in biomarkers. We observed differences between 1-year changes in the MedDiet-VOO intervention and control diet on the activity of platelet activating factor acetylhydrolase in HDLs (+7.5% [95% confidence interval: 0.17; 14.8]) and HDL-bound α1-antitrypsin levels (- 6.1% [-11.8; -0.29]), and between the MedDiet-Nuts intervention and the control arm on non-esterified fatty acid concentrations (-9.3% [-18.1; -0.53]). Large MedDiet adherence increments were associated with less fibrinogen (-9.5% [-18.3; -0.60]) and non-esterified fatty acid concentrations (-16.7% [-31.7; -1.74]). Increases in nut, fruit, vegetable, and fatty fish consumption, and decreases in processed meat intake were linked to beneficial changes in atherothrombosis biomarkers. Conclusion. Following a MedDiet improved atherothrombosis biomarkers in high cardiovascular risk individual

Association between serum ferritin and osteocalcin as a potential mechanism explaining the iron-induced insulin resistance

Background: Increased iron stores are associated with increased risk of type 2 diabetes, however, the mechanisms underlying these associations are poorly understood. Because a reduction of circulating osteocalcin levels after iron overload have been demonstrated in cell cultures, and osteocalcin is related to glucose and insulin metabolism, the ironinduced osteocalcin reductions could contribute to explain the role of iron metabolism in the development of type 2 diabetes mellitus. Objective: To analyzed the associations between serum total and uncarboxylated osteocalcin and adiponectin concentrations with serum ferritin and soluble transferrin receptor (sTfR) in elderly subjects. Design: We evaluated a total of 423 subjects from the PREDIMED cohort in a population-based cross-sectional analysis. Extensive clinical, nutritional and laboratory measurements, including total and uncarboxylated osteocalcin, adiponectin, ferritin and sTfR were recorded. Results: Serum ferritin was positively correlated with increased glucose and insulin circulating levels but also with HOMA-IR, and was inversely associated with total osteocalcin and adiponectin. A regression analysis revealed that serum ferritin and transferrin receptor levels were significantly associated with a decrease in total and uncarboxylated osteocalcin. Serum sTfR levels were associated with lower uncarboxylated osteocalcin levels in the whole-study subjects and remained significant only in the IFG (impaired fasting glucose) individuals. Conclusions: We described, for the first time, an inverse association between serum ferritin and sTfR with osteocalcin and extend previous results on adiponectin, thus supporting that factors related to iron metabolism could contribute to the insulin resistance and the development of type 2 diabetes mellitus. Trial Registration: Controlled-Trials.com ISRCTN35739639 ,http://www.controlled-trials.com/ISRCTN35739639.

Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk

BACKGROUND: Vitamin K has been related to glucose metabolism, insulin sensitivity and diabetes. Because inflammation underlies all these metabolic conditions, it is plausible that the potential role of vitamin K in glucose metabolism occurs through the modulation of cytokines and related molecules. The purpose of the study was to assess the associations between dietary intake of vitamin K and peripheral adipokines and other metabolic risk markers related to insulin resistance and type 2 diabetes mellitus. METHODS: Cross-sectional and longitudinal assessments of these associations in 510 elderly participants recruited in the PREDIMED centers of Reus and Barcelona (Spain). We determined 1-year changes in dietary phylloquinone intake estimated by food frequency questionnaires, serum inflammatory cytokines and other metabolic risk markers. RESULTS: In the cross-sectional analysis at baseline no significant associations were found between dietary phylloquinone intake and the rest of metabolic risk markers evaluated, with exception of a negative association with plasminogen activator inhibitor-1. After 1-year of follow-up, subjects in the upper tertile of changes in dietary phylloquinone intake showed a greater reduction in ghrelin (-15.0%), glucose-dependent insulinotropic peptide (-12.9%), glucagon-like peptide-1 (-17.6%), IL-6 (-27.9%), leptin (-10.3%), TNF (-26.9%) and visfatin (-24.9%) plasma concentrations than those in the lowest tertile (all p<0.05). CONCLUSION: These results show that dietary phylloquinone intake is associated with an improvement of cytokines and other markers related to insulin resistance and diabetes, thus extending the potential protection by dietary phylloquinone on chronic inflammatory diseases. TRIAL REGISTRATION: http://www.controlled-trials.com as ISRCTN35739639

Heme iron intake and risk of new-onset diabetes in a Mediterranean population at high risk of cardiovascular disease: an observational cohort analysis

BACKGROUND: Several epidemiological studies have observed an increased risk of type 2 diabetes mellitus (T2DM) among subjects with a higher consumption of red and processed meat. Heme iron intake has been directly associated with a higher risk of T2DM in healthy adult Chinese and U.S populations. The objective of the present study was to evaluate the association between heme iron intake and the incidence of T2DM in a Mediterranean population at high cardiovascular risk. METHODS: We assessed a subset of participants in the PREDIMED trial as an observational cohort, followed up for a maximum of eight years. We initially included 1073 non-diabetic subjects (57.1% women) aged 67.3 ± 6.0 years, at high cardiovascular risk. Diet was assessed at the study baseline using a validated, semi-quantitative food frequency questionnaire. RESULTS: During the follow-up period 131 diabetics were newly diagnosed. The risk of developing T2DM was assessed using baseline heme iron intake and proportional hazard models, first unadjusted, then adjusted for energy, and finally adjusted for dietary, anthropometric, socio-demographic and lifestyle variables. Significant direct associations with the incidence of T2DM were found for heme iron (Hazard Ratio [HR] 1.30, 95% confidence interval [CI], 1.02 to 1.66). Secondarily, we have also observed that coffee (HR:0.93, 95% CI, 0.89 to 0.98) and alcoholic beverages (HR: 1.02, 95% CI, 1.01 to 1.04) were also found to reduce and increase the risk of T2DM, respectively. CONCLUSION: High dietary intake of heme iron was associated with an increased risk of developing T2DM in a Mediterranean population at high cardiovascular risk. TRIAL REGISTRATION: Identifier: ISRCTN35739639