Papers by José Lopez Miranda

European Journal of Nutrition
Purpose Diabetes remission is a phenomenon described in the context of drastic weight loss due to... more Purpose Diabetes remission is a phenomenon described in the context of drastic weight loss due to bariatric surgery or low-calorie diets. Evidence suggests that increasing the intake of plant protein could reduce the risk of type 2 diabetes. We sought for association between changes in plant protein intake in the context of 2 healthy diets without weight loss nor glucose-lowering medication, and diabetes remission in coronary heart disease patients from the CORDIOPREV study. Methods Newly diagnosed type 2 diabetes participants without glucose-lowering treatment were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was assessed with a median follow-up of 60 months according to the ADA recommendation. Information on patient's dietary intake was collected using food-frequency questionnaires. At first year of intervention, 177 patients were classified according to changes in plant protein consumption into those who increased or decreased its intake,...

Environmental Health
Background Research related to sustainable diets is is highly relevant to provide better understa... more Background Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment. Aim To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population. Design and population Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed. Methods Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expre...

Frontiers in Nutrition
BackgroundMetabolic syndrome (MetS) worsens quality of life and increases mortality. Dissatisfact... more BackgroundMetabolic syndrome (MetS) worsens quality of life and increases mortality. Dissatisfaction with weight in patients with MetS may modify the effect of lifestyle interventions to achieve changes in health-related behaviors.ObjectiveTo assess 1-year changes in cardiovascular risk scores, self-perceived general health and health-related behaviors according to observed changes in desired weight loss during the first year of intervention in a large cardiovascular prevention trial.DesignProspective analysis of the PREDIMED-PLUS trial, including 5,499 adults (55–75 years old) with overweight or obesity at baseline.MethodsThe desired weight loss was the difference between ideal and measured weight. Tertiles of change in desired weight loss (1 year vs. baseline) were defined by the following cut-off points: ≥0.0 kg (T1, n = 1,638); 0.0 to −4.0 kg (T2, n = 1,903); ≤−4.0 kg (T3, n = 1,958). A food frequency questionnaire assessed diet and the Minnesota-REGICOR questionnaire assessed p...

International Journal of Environmental Research and Public Health, 2020
The main objective of this study was to examine the relationship between the level of physical ac... more The main objective of this study was to examine the relationship between the level of physical activity (PA) and the degree of obesity with health-related quality of life (HRQoL) in individuals with metabolic syndrome (MetS) who participated in the Predimed-Plus study. A total of 6875 subjects between 55 and 75 years of age with MetS were selected and randomized in 23 Spanish centers. Subjects were classified according to categories of body mass index (BMI). PA was measured with the validated Registre Gironí del Cor (REGICOR) questionnaire and subjects were classified according to their PA level (light, moderate, vigorous) and the HRQoL was measured with the validated short-form 36 (SF-36) questionnaire. By using the ANOVA model, we found a positive and statistically significant association between the level of PA and the HRQoL (aggregated physical and mental dimensions p < 0.001), but a negative association with higher BMI in aggregated physical dimensions p < 0.001. Furtherm...

Nutrients, 2019
A growing interest has emerged in the beneficial effects of plant-based diets for the prevention ... more A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epica...

Nutrients, 2019
Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on card... more Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on cardiovascular disease (CVD) remains unclear in individuals at high CVD risk. Objective: To assess the association between fat intake and MetS components in an adult Mediterranean population at high CVD risk. Design: Baseline assessment of nutritional adequacy in participants (n = 6560, men and women, 55–75 years old, with overweight/obesity and MetS) in the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial. Methods: Assessment of fat intake (total fat, monounsatured fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, α-linolenic acid, and ω-3 FA) using a validated food frequency questionnaire, and diet quality using 17-item Mediterranean dietary questionnaire and fat quality index (FQI). Results: Participants in the highest quintile of total dietary fat intake showed lower intake of energy, carbohydra...
Atherosclerosis: X, 2019
There is a mismatch in clinical and genetic familial hypercholesterolemia diagnosis. • Familial h... more There is a mismatch in clinical and genetic familial hypercholesterolemia diagnosis. • Familial hypercholesterolemia is a syndrome including several entities. • Monogenic and polygenic familial hypercholesterolemia determines high vascular risk. • Familial hypercholesterolemia diagnosis has implications to access new therapies. • A new classification including all FH genotypes and phenotypes is warranted.

Nutrients, Jan 21, 2016
Whether the content of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (... more Whether the content of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) could differently influence postprandial triglycerides (TG) is unknown. We examined possible differences in the postprandial TG response to fat tolerance tests (FTTs), in which SFA or unsaturated fatty acids were used. Crossover clinical trials investigating the effects of FTTs containing SFA and unsaturated fats on postprandial triglyceridemia in databases from 1994 until 2016 were searched. Of 356 studies, 338 were excluded and 18 were considered. TG net incremental areas under the curve were calculated using time-points or changes from baseline. Pooled effects of standardized mean differences and I² test were used. In 12 studies, responses to SFA versus PUFA meals, and in 16 studies versus MUFA meals were compared. Over 4 hours, no differences between SFA and unsaturated fats were observed. Over 8 hours a lower response to PUFA (SMD -2.28; 95%CI -4.16, -0.41) and a trend to lowe...

The American journal of clinical nutrition, 2004
Nuclear transcription factor kappaB (NF-kappaB) plays an important role in atherosclerosis by mod... more Nuclear transcription factor kappaB (NF-kappaB) plays an important role in atherosclerosis by modulating gene expression. Postprandial lipemia has been correlated with an increase in NF-kappaB activation in vascular cells and it is associated with an increase in postprandial triacylglycerol-rich lipoproteins, which are involved in the development of atherosclerotic plaque. The objective of this study was to determine the effect of the intakes of 3 different foods with different fat compositions on the postprandial activation of monocyte NF-kappaB. Eight healthy men followed a 4-wk baseline diet and then consumed 3 fat-load meals consisting of 1 g fat/kg body wt (65% fat) according to a randomized crossover design. Each meal had a different fatty acid composition, and the consumption of each meal was separated by 1 wk. The compositions of the 3 test meals were as follows: olive oil meal [22% saturated fatty acids (SFAs), 38% monounsaturated fatty acids (MUFAs), 4% polyunsaturated fat...

The American journal of clinical nutrition, 2007
Oxidative stress associated with postprandial lipemia contributes to endothelial dysfunction, whi... more Oxidative stress associated with postprandial lipemia contributes to endothelial dysfunction, which shifts hemostasis to a more thrombogenic state. We investigated whether a high concentration of phenols in olive oil can partly reverse this phenomenon. Twenty-one hypercholesterolemic volunteers received 2 breakfasts rich in olive oils with different phenolic contents (80 or 400 ppm) according to a randomized, sequential crossover design. Plasma concentrations of lipid fractions, factor VII antigen (FVIIag), activated factor VII (FVIIa), and plasminogen activator inhibitor-1 (PAI-1) activity were measured at baseline and postprandially. Concentrations of FVIIa increased less (P = 0.018) and plasma PAI-1 activity decreased more (P = 0.021) 2 h after the high-phenol meal than after the low-phenol meal. FVIIa concentrations 120 min after intake of the olive oil with a high phenol content correlated positively with fasting plasma triacylglycerols (P = 0.001), area under the curve (AUC) o...
Proceedings of the Nutrition Society, 2008

Apolipoprotein E gene promoter (–219G/T) polymorphism is associated with premature coronary heart disease
Journal of Molecular Medicine, 2001
The relationship of two apolipoprotein (apo) E gene polymorphisms and coronary heart disease (CHD... more The relationship of two apolipoprotein (apo) E gene polymorphisms and coronary heart disease (CHD) was investigated in 118 Finnish families with premature CHD and in 110 healthy control subjects. Affected siblings and probands with premature CHD had higher frequencies of the T allele of the -219G/T promoter polymorphism and the epsilon 4 allele (genotypes epsilon 4/3 or epsilon 4/4) of the apo epsilon 2/epsilon 3/ epsilon 4 polymorphism than those of healthy control subjects. Additionally, when the two apo E gene polymorphisms were combined, affected siblings and probands had a higher frequency of the -219T allele and the epsilon 4 allele combinations than did healthy controls. The -219T and the epsilon 4 alleles both separately and together were associated with higher levels of 2-h glucose in an oral glucose tolerance test. These results indicate that the two polymorphisms of the apo E gene have similar effects on the risk of coronary atherosclerosis in families with premature CHD. This risk was not explained by the effect of apo E gene polymorphisms on cholesterol metabolism, but their effect on cardiovascular risk factor clustering with insulin resistance may be of importance. We conclude that in addition to the epsilon 4 allele, also the -219G/T promoter polymorphism of the apo E gene is associated with early onset CHD.

Different Secretory Response of Pancreatic Isolated Lobules and Dissociated Acini from Hypothyroid Rats to Exogen TRH
Experimental and Clinical Endocrinology & Diabetes, 2009
This paper analyses the effect of hypothyroidism on pancreatic TRH and somatostatin concentration... more This paper analyses the effect of hypothyroidism on pancreatic TRH and somatostatin concentrations, as well as the action of exogen TRH on pancreatic amylase secretion from isolated lobules and dissociated acini of both healthy and hypothyroid rats. In the hypothyroid group, pancreatic TRH and somatostatin increased. In the pancreatic lobules of untreated animals, bethanechol produced stimulatory action that was inhibited by TRH. On the other hand, lobules from hypothyroid rats did not respond to bethanechol stimulation. Acini amylase secretion after bethanechol stimulation was similar in both groups, although hypothyroid animals were more sensitive to the inhibitory effect of TRH. These findings suggest the existence of a factor blocking the amylase secretion in pancreatic lobules. This agent, probably TRH, could be eliminated in the experimental model of dissociated acini.

European Journal of Clinical Nutrition, 2000
The objective of this trial was to compare the effect on the susceptibility of plasma Low Density... more The objective of this trial was to compare the effect on the susceptibility of plasma Low Density Lipoprotein (LDL) to oxidative modi®cations of consumption of two oleic rich diets, prepared with two different plant oils, virgin olive oil (OL) 1 and re®ned high monounsaturated fatty acids (MUFA sun¯ower oil (SU)), with the susceptibility of plasma LDL to oxidation after an National Cholesterol Education Program step 1 (NCEP-I) phase diet. Design: A randomized crossover design. Subjects and interventions: Twenty-two healthy normolipidemic young males consumed an NCEP-I diet for a 4-week period. Subjects were then assigned to two diets each of 4-weeks duration. Group one was placed on an olive oil enriched diet (40% fat, 22% MUFA) followed by a 4-week period of a MUFA diet enriched in sun¯ower oil (40% fat, 22% MUFA). In group two, the order of the diets was reversed. Results: Both MUFA diets induced a decrease in saturated (14 : 0, 16 : 0, and 18 : 0) and an increase in monounsaturated and polyunsaturated n-6 (18 : 2, 20 : 3, and 20 : 5) plasma LDL-phospholipid fatty acids, compared to the NCEP-I diet (P`0.01). No signi®cant differences in lag times were observed between the olive oil and the NCEP-I diet periods. However there was a greater inhibition time (P`0.001) when subjects consumed the MUFA rich sun¯ower oil diet compared to the NCEP-I diet. These differences were probably related to the relative enrichment of plasma LDL particles in a-tocopherol due to the high vitamin E content of the MUFA-rich sun¯ower oil. Indeed, the a-tocopherol content was positively correlated with lag time (r 0.338; P`0.008). Conclusion: Our ®ndings suggest that changes in plasma LDL a-tocopherol content with practical solid-food diets can decrease its susceptibility to oxidation.
The Ala54Thr Polymorphism of the Fatty Acid Binding Protein 2 Gene Does Not Influence Insulin Sensitivity in Finnish Nondiabetic and NIDDM Subjects
Diabetes, 1997
Insulin resistance and hyperinsulinemia are major predictors of NIDDM. Since several studies have... more Insulin resistance and hyperinsulinemia are major predictors of NIDDM. Since several studies have demonstrated that heredity plays a significant role in the development of insulin resistance (1), defects in genes that regulate insulin action could potentially contribute to the risk of NIDDM. A locus on chromosome 4q has been shown to be linked with fasting insulin levels (2), 2-h insulin levels (3,4), and insulin action (2) in Pima Indians and Mexican-Americans, suggesting that the fatty acid binding protein 2 (FABP2) gene is a promising candidate gene for insulin resistance and NIDDM.

The American Journal of Clinical Nutrition, 2009
Background: Progression of the metabolic syndrome (MetS) is determined by genetic and environment... more Background: Progression of the metabolic syndrome (MetS) is determined by genetic and environmental factors. Gene-environment interactions may be important in modulating the susceptibility to the development of MetS traits. Objective: Gene-nutrient interactions were examined in MetS subjects to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and their effects on MetS characteristics. Design: Plasma fatty acid composition, insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ, ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics, and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and Economic Analysis) dietary intervention study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) casecontrol study (http://www.ucd.ie/lipgene). Results: Single SNP effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids, and waist circumference were significantly different between genotypes for 2 SNPs (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both of these SNPs were identified as having degrees of insulin resistance, as measured by the homeostasis model assessment of insulin resistance, that were highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA-dependent association between ADIPOR1 rs10920533 and insulin resistance was replicated in cases with MetS from a separate independent study, which was an association not present in controls. Conclusions: A reduction in plasma SFAs could be expected to lower insulin resistance in MetS subjects who are minor allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized dietary advice to decrease SFA consumption in these individuals may be recommended as a possible therapeutic measure to improve insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00429195.

AGE, 2013
We have investigated whether dietary fat modifies the postprandial oxidative stress in adipose ti... more We have investigated whether dietary fat modifies the postprandial oxidative stress in adipose tissue of elderly people. Twenty participants received three diets for 4 weeks each: SFA-rich diet, Mediterranean (Med) diet enriched in MUFA with virgin olive oil, and a low-fat, high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid from plant origin) (CHO-PUFA diet). After 12 h of fasting, volunteers received a breakfast reflecting the fatty acid composition of the diet ingested in the preceding dietary period. Med diet induced higher postprandial SOD2 and TrxR mRNA levels, and CHO-PUFA diet induced higher GPx1 and TrxR mRNA levels compared with SFA-rich diet. Med and CHO-PUFA breakfasts induced a postprandial increase in plasma reduced glutathione (GSH), and a greater postprandial GSH/oxidized glutathione ratio compared to the SFArich diet. Our study suggests that the consumption of Med and CHO-PUFA diets may reduce postprandial oxidative stress compared to an SFA-rich diet, which may be due to higher antioxidant enzymes gene expression in adipose tissue.

Metabolic Syndrome Features and Excess Weight Were Inversely Associated with Nut Consumption after 1-Year Follow-Up in the PREDIMED-Plus Study
The Journal of Nutrition
Background High nut consumption has been previously associated with decreased prevalence of metab... more Background High nut consumption has been previously associated with decreased prevalence of metabolic syndrome (MetS) regardless of race and dietary patterns. Objectives The aim of this study was to assess whether changes in nut consumption over a 1-y follow-up are associated with changes in features of MetS in a middle-aged and older Spanish population at high cardiovascular disease risk. Methods This prospective 1-y follow-up cohort study, conducted in the framework of the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial, included 5800 men and women (55–75 y old) with overweight/obesity [BMI (in kg/m2) ≥27 and <40] and MetS. Nut consumption (almonds, pistachios, walnuts, and other nuts) was assessed using data from a validated FFQ. The primary outcome was the change from baseline to 1 y in features of MetS [waist circumference (WC), glycemia, HDL cholesterol, triglyceride (TG), and systolic and diastolic blood pressure] and excess weight (body weight and BMI) ...

Nutrients
One-year dietary quality change according to the preceding maximum weight in a lifestyle interven... more One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55–75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible to improve significantly their dietary quality, assessed by adherence to Mediterranean diet, DII and both healthful and unhealthful provegetarian patterns. People at maximum weight are the most benefitted in the short term by a weight management program. Long term weight loss efforts may also redu...

Journal of Clinical Medicine, Nov 22, 2019
Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent... more Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa.
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Papers by José Lopez Miranda