Municipal Institute for Medical Research IMIM

Barcelona, Spain

Municipal Institute for Medical Research IMIM

Barcelona, Spain
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Corella D.,University of Valencia | Corella D.,CIBER ISCIII | Ortega-Azorin C.,University of Valencia | Ortega-Azorin C.,CIBER ISCIII | And 25 more authors.
PLoS ONE | Year: 2012

Background: Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. Objective: To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. Methods: Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed. Results: FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR = 1.07; 95%CI 1.01-1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/-SE: -0.57+/-0.16 g/d per-score-allele; P = 0.001). Conclusion: Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI. © 2012 Corella et al.


Ortega-Azorin C.,University of Valencia | Ortega-Azorin C.,CIBER ISCIII | Sorli J.V.,University of Valencia | Sorli J.V.,CIBER ISCIII | And 27 more authors.
Cardiovascular Diabetology | Year: 2012

Background: Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet).Methods: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed.Results: Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern.Conclusions: These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition. © 2012 Ortega-Azorín et al.; licensee BioMed Central Ltd.


Babio N.,Rovira i Virgili University | Babio N.,CIBER ISCIII | Ibarrola-Jurado N.,Rovira i Virgili University | Ibarrola-Jurado N.,CIBER ISCIII | And 15 more authors.
PLoS ONE | Year: 2013

Background: The Metabolic Syndrome (MetS) is a cluster of metabolic abnormalities that includes hyperglucemia, hypertension, dyslipidemia and central obesity, conferring an increased risk of cardiovascular disease. The white blood cell (WBC) count has been proposed as a marker for predicting cardiovascular risk. However, few prospective studies have evaluated the relationship between WBC subtypes and risk of MetS. Methods: Participants were recruited from seven PREDIMED study centers. Both a baseline cross-sectional (n = 4,377) and a prospective assessment (n = 1,637) were performed. Participants with MetS at baseline were excluded from the longitudinal analysis. The median follow-up was 3.9 years. Anthropometric measurements, blood pressure, fasting glucose, lipid profile and WBC counts were assessed at baseline and yearly during the follow-up. Participants were categorized by baseline WBC and its subtype count quartiles. Adjusted logistic regression models were fitted to assess the risk of MetS and its components. Results: Of the 4,377 participants, 62.6% had MetS at baseline. Compared to the participants in the lowest baseline sex-adjusted quartile of WBC counts, those in the upper quartile showed an increased risk of having MetS (OR, 2.47; 95%CI, 2.03-2.99; P-trend<0.001). This association was also observed for all WBC subtypes, except for basophils. Compared to participants in the lowest quartile, those in the top quartile of leukocyte, neutrophil and lymphocyte count had an increased risk of MetS incidence. Leukocyte and neutrophil count were found to be strongly associated with the MetS components hypertriglyceridemia and low HDL-cholesterol. Likewise, lymphocyte counts were found to be associated with the incidence of the MetS components low HDL-cholesterol and high fasting glucose. An increase in the total WBC during the follow-up was also associated with an increased risk of MetS. Conclusions: Total WBC counts, and some subtypes, were positively associated with MetS as well as hypertriglyceridemia, low HDL-cholesterol and high fasting glucose, all components of MetS. Trial registration: Controlled-Trials.comISRCTN35739639. © 2013 Babio et al.


Bullo M.,Rovira i Virgili University | Bullo M.,CIBER ISCIII | Garcia-Aloy M.,Rovira i Virgili University | Garcia-Aloy M.,CIBER ISCIII | And 6 more authors.
Journal of Nutrition, Health and Aging | Year: 2011

Objective: The aim of this study is to determine whether metabolic syndrome, its individual components, or the presence of type 2 diabetes mellitus are associated with a better bone status estimated by quantitative ultrasound at the calcaneus. Design: Cross-sectional study. Setting: Outpatient clinics. Participants: 251 elderly subjects at high cardiovascular risk from the PREDIMED study were included. Measurements: MetS was defined according to the ATPIII diagnosis criteria. Calcaneus quantitative ultrasound (QUS) assessment was performed using the Sahara system. Results: Subjects with MetS showed significantly lower 24-hour urinary deoxypyridinoline/creatinine (u-DPD/creatinine) levels and higher broadband ultrasound attenuation, and a tendency to higher bone mineral density (BMD) and quantitative ultrasound index (QUI) than their counterparts. Individuals with type 2 diabetes mellitus (T2DM) showed a significantly higher bone broadband ultrasound attenuation (BUA) and QUI than their non-diabetic counterparts, despite they shown a higher prevalence of osteoporotic fractures. Multiple linear regression analyses showed that quantitative ultrasound parameters were positively associated with the metabolic syndrome and T2DM. Of the bone biochemical markers, only u-DPD/creatinine was related to MetS, abdominal obesity, hypertriglyceridemia component of the MetS, and the number of features that define the MetS. Conclusion: This is the first study showing a positive association between MetS or T2DM with better bone status and lower bone resorption markers measured by quantitative ultrasound. Our results suggest that metabolic abnormalities have a positive effect on healthy bone in elderly subjects at high risk of cardiovascular disease. © 2011 Serdi and Springer Verlag France.


Vazquez-Fresno R.,University of Barcelona | Llorach R.,University of Barcelona | Urpi-Sarda M.,University of Barcelona | Khymenets O.,University of Barcelona | And 10 more authors.
Metabolomics | Year: 2015

The development of robust biomarkers of consumption would improve the classification of participants with regard to their dietary exposure. In addition, validation of them in free-living individuals remains an important challenge. The aim of this study is to assess wine intake biomarkers using an NMR metabolomic approach to measure the utility of these biomarkers in a wine interventional study (WIS, n = 56) and also to evaluate them in a free-living individuals (PREDIMED study, n = 91). Nine metabolites showed a significantly higher presence in urinary excretion in WIS after wine intake: five food metabolome metabolites (tartrate, ethyl glucuronide [EtG], 2,3-butanediol, mannitol, and ethanol); one related to the endogenous response to wine exposure (3-methyl-2-oxovalerate) and three unidentified compounds. Receiver operating characteristic (ROC) curve for each single metabolite were evaluated and exhibited areas under the curves (AUC) between 67.4 and 86.3 % when they were evaluated individually. Then, a logistic regression model was fitted to generate a combined-biomarkers model using these metabolites. The model generated which included tartrate-EtG, showed an AUC of 90.7 % in WIS. Similarly, the AUC in the PREDIMED study was 92.4 %. Results showed that a model combining tartrate-EtG is more useful for evaluating exposure to wine than single biomarkers, both in interventional studies and epidemiological data. To our knowledge, this is the first time that a combined-biomarker model using an NMR platform in wine biomarkers’ research has been generated and reproduced in a free-living population. © 2014, Springer Science+Business Media New York.


Casas R.,University of Barcelona | Casas R.,CIBER ISCIII | Sacanella E.,University of Barcelona | Sacanella E.,CIBER ISCIII | And 18 more authors.
PLoS ONE | Year: 2014

Background: Adherence to the Mediterranean diet (MD) is associated with reduced morbidity and mortality due to cardiovascular disease. However, how the MD exerts its effects is not fully known. Aim: To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED (Prevención con Dieta Mediterránea) study. Methods: A total of 164 participants at high risk for cardiovascular disease were randomized into three diet groups: MD supplemented with 50 mL/d of extra virgin olive oil (MD+EVOO) or 30 g/d of nuts (MD+Nuts) and a low-fat diet. Changes in classical cardiovascular risk factors, inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention. Results: Compared to participants in the low-fat diet group, those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic (6 mmHg) and diastolic (3 mmHg) blood pressure (P = 0.02; both), as well as a reduction of 10% and 8% in LDL-cholesterol (P = 0.04), respectively. Patients in the MD+Nuts group showed a significant reduction of 34% in CD40 expression on monocyte surface compared to low-fat diet patients (P = 0.03). In addition, inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45% and 35% and 95% and 90% in the MD+EVOO and MD+Nuts groups, respectively (P<0.05; all) compared to the low-fat diet group. Likewise, sICAM and P-selectin were also reduced by 50% and 27%, respectively in the MD+EVOO group (P = 0.04) and P-selectin by 19% in MD+Nuts group (P = 0.04) compared to the low-fat diet group. Conclusions: Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain, at least in part, the protective role of MD against ischemic heart disease. Trial Registration: www.controlled-trials.com ISRCTN35739639 © 2014 Casas et al.


Medina-Remon A.,University of Barcelona | Medina-Remon A.,CIBER ISCIII | Medina-Remon A.,Institute Salud Carlos III | Zamora-Ros R.,University of Barcelona | And 35 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2011

Background and aims: Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk. Methods and results: Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin-Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), coffee or wine after adjusting for potential confounders. The intake of 100. g of F&V (Beta = 0.150; P< 0.001) had a greater contribution to TPE than 100. mL of coffee (Beta = 0.141;. P= 0.001), and the latter two foods contributed more than the consumption of 100. mL of wine (Beta = 0.120;. P= 0.019). An inverse association was observed between urinary TPE and the prevalence of hypertension. Participants in the highest quartile of urinary TPE had a reduced prevalence of hypertension compared to those in the lowest quartile (Odds Ratio = 0.64; 95% confidence interval 0.45 to 0.92; P= 0.015). Systolic and diastolic BP were inversely associated with urinary TPE after adjustment for potential confounders (P= 0.024 and P= 0.003, respectively). Conclusions: Polyphenol intake, assessed via TPE in urine, was negatively associated with BP levels and prevalence of hypertension in an elderly Mediterranean population at high cardiovascular risk. Participants with the highest intake of polyphenol-rich foods showed the lowest BP measurements. © 2009 Elsevier B.V.


Tresserra-Rimbau A.,University of Barcelona | Tresserra-Rimbau A.,CIBER ISCIII | Rimm E.B.,Harvard University | Medina-Remon A.,CIBER ISCIII | And 34 more authors.
BMC Medicine | Year: 2014

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk.Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models.Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids).Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.Clinical trial registration: ISRCTN35739639. © 2014 Tresserra-Rimbau et al.; licensee BioMed Central Ltd.

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