Association between Diet Quality and Risk of Type 2 Diabetes Mellitus in Patients with Coronary Heart Disease: Findings from the CORDIOPREV Study.

The incidence of type 2 diabetes mellitus (T2DM) is growing in Western countries. Nutritional interventions that promote high-quality dietary patterns could help reverse this trend. We aimed to evaluate whether changes in Nutrient-Rich Food Index 9.3 (NRF9.3) were related to the risk of developing T2DM in patients with coronary heart disease (CHD). The study was carried out in the context of two healthy dietary interventions (a Mediterranean and a low-fat diet). For this purpose, we evaluated all the patients in the CORDIOPREV study without T2DM at baseline. Data were obtained during the first 5 years of dietary intervention. The score was calculated using the Food Frequency Questionnaires at baseline and after 1 year of intervention. After 5 years of follow-up, 106 patients developed T2DM (incident-T2DM), while 316 subjects did not (non-T2DM). Total NRF9.3 score and changes during the first year of intervention were compared between incident-T2DM and non-T2DM. Incident-T2DM showed less improvement in NRF9.3 than non-T2DM (p = 0.010). In the multi-adjusted Cox proportional hazard study, patients with greater improvement in NRF9.3 had over 50% less risk of developing T2DM compared with the lowest tertile (HR 2.10, 95%, CI = 1.12-3.56). In conclusion, improved diet quality in terms of nutrient density after the dietary intervention was associated with a lower risk of T2DM in patients with CHD.

Telomere Maintenance Is Associated with Type 2 Diabetes Remission in Response to a Long-Term Dietary Intervention without Non-Weight Loss in Patients with Coronary Heart Disease: From the CORDIOPREV Randomized Controlled Trial.

In order to evaluate whether telomere maintenance is associated with type 2 diabetes remission, newly diagnosed type 2 diabetes patients without glucose-lowering treatment (183 out of 1002) from the CORDIOPREV study (NCT00924937) were randomized to consume a Mediterranean or low-fat diet. Patients were classified as Responders, those who reverted from type 2 diabetes during the 5 years of dietary intervention (n = 69), and Non-Responders, who did not achieve diabetes remission by the end of the follow-up period (n = 104). We found no differences in diabetes remission between the two diets, and we determined telomere length (TL) by measuring qPCR, telomerase activity using the TRAP assay, and direct redox balance based on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) via colorimetric assay. Responders exhibited higher baseline TL in comparison with Non-Responders (p = 0.040), and a higher TL at baseline significantly predicted a higher probability of type 2 diabetes remission (OR 2.13; 95% CI, 1.03 to 4.41). After the dietary intervention, Non-Responders showed significant telomere shortening (-0.19, 95% CI -0.32 to 0.57; p = 0.005). Telomere shortening was significantly pronounced in type 2 diabetes patients with a worse profile of insulin resistance and/or beta-cell functionality: high hepatic insulin resistance fasting, a high disposition index (-0.35; 95% CI, -0.54 to -0.16; p < 0.001), and a low disposition index (-0.25; 95% CI, -0.47 to -0.01; p = 0.037). In addition, changes in TL were correlated to the GSH/GSSG ratio. Responders also showed increased telomerase activity compared with baseline (p = 0.048), from 0.16 (95% CI, 0.08 to 0.23) to 0.28 (95% CI, 0.15 to 0.40), with a more marked increase after the dietary intervention compared with Non-Responders (+0.07; 95% CI, -0.06-0.20; p = 0.049). To conclude, telomere maintenance may play a key role in the molecular mechanisms underlying type 2 diabetes remission in newly diagnosed patients. However, further larger-scale prospective studies are necessary to corroborate our findings.

Dietary antioxidant intake reduces carotid intima-media thickness in coronary heart disease patients: From the CORDIOPREV study.

BACKGROUND: Atherosclerosis is the leading underlying cause of coronary heart disease (CHD). In patients with CHD, intima-media thickness of common carotid arteries (IMT-CC) is a reliable, validated, and non-invasive marker of the progression of atherosclerosis. Dietary intervention may affect IMT-CC evolution through different pathways. There is a lack of clinical trials evaluating the effect of total dietary antioxidant content of diets on IMT-CC, especially in patients with CHD. OBJECTIVE: We evaluated the correlation between the diet's total antioxidant content and the changes in IMT-CC produced after 5 years of dietary intervention following two healthy diet models (Mediterranean diet and low-fat diet). We also evaluated whether the diet's total antioxidant content was related to the total redox capacity of the participants. METHODS: From the total participants of the CORDIOPREV study (clinical trial register NCT00924937), 805 participants completed the IMT-CC measurement and the dietary antioxidant evaluation at baseline and after 5 years of dietary intervention. IMT-CC was carried out by ultrasound and the dietary antioxidant evaluation was performed by the Dietary Antioxidant Index (DAI). Additionally, direct redox balance was evaluated in a subset of population by the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) by colorimetric assay. RESULTS: We observed an inverse correlation between evolution of DAI and IMT-CC after 5-years of dietary intervention. The mean of the DAI index augmented in the Mediterranean Diet group, whereas it decreased in the Low-fat group. DAI was correlated to the GSH/GSSG ratio, supporting DAI as an adequate estimator of diet's antioxidant content. When looking for individual components of the DAI that were associated to the changes in IMT-CC, an inverse correlation was found for carotenoids, vitamin E, vitamin C, and zinc and the IMT-CC. CONCLUSIONS: Our study indicates that, after five years of dietary intervention, changes in DAI inversely correlate with changes in IMT-CC in patients with CHD. Overall effect of Mediterranean diet resulted in an increase of DAI, conversely to low-fat. Specific elements included in the DAI index were inversely correlated with IMT-CC.

Association between telomere length and intima-media thickness of both common carotid arteries in patients with coronary heart disease: From the CORDIOPREV randomized controlled trial.

BACKGROUND AND AIMS: A critical telomere length (TL) is associated with cardiovascular mortality. Dietary habits have been demonstrated to affect cardiovascular risk. However, it remains unclear how exactly TL determines the response to specific dietary approaches in the reduction of arterial injury. We aimed to evaluate whether TL was associated with the progression of arterial injury (assessed by intima-media thickness of both common carotid arteries: IMT-CC), after long-term consumption of two healthy dietary models in patients with coronary heart disease (CHD). METHODS: From the 1002 CHD patients of the CORDIOPREV study, 903 completed IMT-CC and TL evaluation at baseline and were randomized to follow a Mediterranean diet or a low-fat diet for 5 years. RESULTS: Patients at risk of short TL (TL < 20th percentile) presented an elevated IMT-CC, (0.79 ± 0.17 vs patients at non-risk 0.74 ± 0.17 p < 0.001). TL and IMT-CC showed an inverse association (ß = -0.035, p = 0.002). Patients who consumed a Mediterranean diet, regardless of the risk of short TL, showed a significant decrease in IMT-CC, with a higher reduction in those patients with risk of short TL (-0.03 ± 0.11, p = 0.036). TL (ß = 0.019, p = 0.024), age (ß = -0.001, p = 0.031), energy intake (ß = -0.000, p = 0.036), use of statins (ß = -0.027, p = 0.028) and allocation into the Mediterranean diet (vs low-fat diet) (ß = -0.024, p = 0.003) were significant contributors to changes in IMT-CC. CONCLUSIONS: Patients who had a reduced TL exhibited a greater decrease in IMT-CC after consuming a Mediterranean diet.

Effect of 8-Week Consumption of a Dietary Pattern Based on Fruit, Avocado, Whole Grains, and Trout on Postprandial Inflammatory and Oxidative Stress Gene Expression in Obese People.

Overweight and obesity constitute a major global public health problem. Healthy dietary patterns induce changes at the molecular level. Currently, there are no studies evaluating the effect of a diet based on fruit, avocado, whole grains, and trout (FAWGT diet) on the expression of obesity-related genes. This randomized controlled crossover study included 44 obese Colombians with BMI ≥30 kg/m2 who followed either a FAWGT diet or a usual diet (UD) characterized by a high intake of saturated fat and foods rich in processed carbohydrates. After 8 weeks of intervention, a postprandial expression study of inflammation and oxidative stress-related genes was carried out with a real-time PCR. The intervention with a FAWGT diet decreased the expression of inflammatory (NFKB1, IL6, IL1ß) and oxidative stress (NFE2L2) genes compared with the intake of the UD. Finally, the postprandial expression of NFkB1 was positively correlated with triglyceride levels after a dietary intervention with the FAWGT diet and the IL1ß gene, and likewise with insulin levels after following the usual diet. The consumption of the FAWGT diet for 8 weeks reduced the inflammatory status; thus, it can be considered a valid alternative to other healthy diets, since it induces beneficial changes on the genes involved in inflammation and oxidative stress in obese people.

Effect of the Mediterranean diet and probiotic supplementation in the management of mild cognitive impairment: Rationale, methods, and baseline characteristics.

Introduction: Mild cognitive impairment (MCI) can progress to Alzheimer's disease (AD). When MCI is not properly controlled, the speed of deterioration can dramatically increase. Reduction of oxidative stress/inflammation and the modulation of the gut-brain axis could be new potential therapeutic targets for the prevention and treatment of AD. Consumption of specific nutrients, diets and probiotic supplementation have been evaluated for neurodegenerative disorders. We focus on a detailed description of the study methods and baseline characteristics of a clinical trial aiming to evaluate the efficacy of a combined nutritional intervention, i.e., a Mediterranean diet with probiotics, on cognitive capacity in a population with MCI. Methods: In this randomized, latin-square crossover, double-blind, and controlled dietary intervention trial (clinicaltrials.gov NCT05029765), 47 MCI patients were randomized to consume three dietary interventions for 24-weeks each: (1) A Mediterranean diet supplemented with probiotics (109 colony-forming units of Lactobacillus rhamnosus and Bifidobacterium longum); (2) A Mediterranean diet + placebo; and (3) A Healthy diet according to the World Health Organization (WHO) recommendations. Participants will be evaluated before and after each of the three intervention periods (each 24-weeks, with a total of 72-weeks) for adherence to the assigned diet, blood tests, cognitive performance, gut microbiota analysis and functional neuroimaging studies. Results: Fifty patients, ≥60 years-old and diagnosed with MCI, underwent randomization. A total of 47 patients completed follow-up dietary interventions (57.4% males), with a good glycemic control (HbA1c 5.8 ± 0.1%, fasting glucose and insulin 99.7 ± 3.3 mg/dL and 10.4 ± 0.9 mU/L, respectively), elevated systolic blood pressure (136.9 ± 2.1 mmHg) and increased degree of inflammation (high-sensitivity C-reactive protein, 8.8 ± 0.9 mg/dL). Baseline adherence to the Mediterranean diet was medium (7.5 ± 0.3 points on the score that ranged from 0 to 14 points). Conclusion: The results of this clinical study would provide more evidence on the need for dietary therapeutic strategies, for clinical and individual practice, in the management of MCI patients to reduce the risk of AD development. Targeting lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05029765].

Metabolomics analysis of type 2 diabetes remission identifies 12 metabolites with predictive capacity: a CORDIOPREV clinical trial study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is one of the most widely spread diseases, affecting around 90% of the patients with diabetes. Metabolomics has proven useful in diabetes research discovering new biomarkers to assist in therapeutical studies and elucidating pathways of interest. However, this technique has not yet been applied to a cohort of patients that have remitted from T2DM. METHODS: All patients with a newly diagnosed T2DM at baseline (n = 190) were included. An untargeted metabolomics approach was employed to identify metabolic differences between individuals who remitted (RE), and those who did not (non-RE) from T2DM, during a 5-year study of dietary intervention. The biostatistical pipeline consisted of an orthogonal projection on the latent structure discriminant analysis (O-PLS DA), a generalized linear model (GLM), a receiver operating characteristic (ROC), a DeLong test, a Cox regression, and pathway analyses. RESULTS: The model identified a significant increase in 12 metabolites in the non-RE group compared to the RE group. Cox proportional hazard models, calculated using these 12 metabolites, showed that patients in the high-score tercile had significantly (p-value < 0.001) higher remission probabilities (Hazard Ratio, HR, high versus low = 2.70) than those in the lowest tercile. The predictive power of these metabolites was further studied using GLMs and ROCs. The area under the curve (AUC) of the clinical variables alone is 0.61, but this increases up to 0.72 if the 12 metabolites are considered. A DeLong test shows that this difference is statistically significant (p-value = 0.01). CONCLUSIONS: Our study identified 12 endogenous metabolites with the potential to predict T2DM remission following a dietary intervention. These metabolites, combined with clinical variables, can be used to provide, in clinical practice, a more precise therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00924937.

Diet and SIRT1 Genotype Interact to Modulate Aging-Related Processes in Patients with Coronary Heart Disease: From the CORDIOPREV Study.

We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases.

Chronodisruption and diet associated with increased cardiometabolic risk in coronary heart disease patients: the CORDIOPREV study.

Individuals with evening chronotypes are prone to suffer chronodisruption and display worse lifestyle habits than morning-types, exhibiting higher cardiovascular diseases (CVD). However, it is unknown whether CVD patients, who are evening chronotypes, have higher cardiometabolic risk than morning-types. This study explored whether individual chronotypes were associated with cardiometabolic risk in patients from the CORDIOPREV study (n = 857). We also investigated whether potential associations were moderated by long-term consumption of two healthy diets (Mediterranean and Low-fat diets). This population was classified into chronotypes using the Morningness-Eveningness Questionnaire. Seven-day daily rhythms in wrist temperature (T), rest-activity (A) and position (P) were recorded in a subset of patients (n = 168), and an integrative variable TAP was determined. Metabolic Syndrome (MetS) was determined at baseline, and metabolic and inflammation markers were measured at baseline and yearly during the 4 years of follow-up. Differences in several lifestyle factors were analyzed according to chronotype. At all times, evening-types had higher triglycerides, C-reactive protein and homocysteine and lower high density lipoprotein cholesterol than morning-types (P < 0.05). Evening-types had a higher prevalence of MetS (OR 1.58 IC 95% [1.10 - 2.28], P = 0.01). Moreover, they were more sedentary, displayed less and delayed physical activity and ate and slept later. In addition, evening-types had lower amplitude, greater fragmentation, lower robustness and less stable circadian pattern at TAP (P < 0.01), all related to a less healthy circadian pattern. In conclusion, evening-types with CVD had higher cardiometabolic risk and less robust circadian-related rhythms than morning-types, regardless of the nutritional intervention.

Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease.

Preadipocytes are crucial for healthy adipose tissue expansion. Preadipocyte differentiation is altered in obese individuals, which has been proposed to contribute to obesity-associated metabolic disturbances. Here, we aimed at identifying the pathogenic processes underlying impaired adipocyte differentiation in obese individuals with insulin resistance (IR)/type 2 diabetes (T2D). We report that down-regulation of a key member of the major spliceosome, PRFP8/PRP8, as observed in IR/T2D preadipocytes from subcutaneous (SC) fat, prevented adipogenesis by altering both the expression and splicing patterns of adipogenic transcription factors and lipid droplet-related proteins, while adipocyte differentiation was restored upon recovery of PRFP8/PRP8 normal levels. Adipocyte differentiation was also compromised under conditions of endoplasmic reticulum (ER)-associated protein degradation (ERAD) hyperactivation, as occurs in SC and omental (OM) preadipocytes in IR/T2D obesity. Thus, targeting mRNA splicing and ER proteostasis in preadipocytes could improve adipose tissue function and thus contribute to metabolic health in obese individuals.

Alternative Foods in Cardio-Healthy Dietary Models That Improve Postprandial Lipemia and Insulinemia in Obese People.

Obesity is one of the major health problems worldwide. Following healthy dietary patterns can be difficult in some countries due to the lack of availability of certain foods; thus, alternative foods are needed. Our aim was to evaluate the effect of a dietary pattern consisting of fruit, avocado, whole grains, and trout (FAWGT) on postprandial insulinemia and lipemia in obese Colombian subjects. A randomized controlled crossover study was conducted, in which 44 subjects with BMI ≥ 30 kg/m2 followed either a FAWGT diet or a diet high in saturated fat and rich in processed carbohydrates. Levels of lipids and carbohydrates were measured during the postprandial state. The FAWGT diet reduced fasting insulin, VLDL, and HOMA-IR after 8 weeks (p < 0.05), while there was a lower postprandial increase in TG, VLDL, and insulin levels after both acute and chronic intake of FAWGT diet (p < 0.05). The intake of FAWGT-diet was characterized by high consumption of foods rich in fiber, MUFAs, and vitamins C and E (p < 0.05). The consumption of a diet composed of fruit, avocado, whole grains, and trout has emerged as a valid alternative to the foods included in other heart-healthy diets since it improves postprandial lipemia and insulinemia in obese people and has similar beneficial effects to these healthy models.

A set of miRNAs predicts T2DM remission in patients with coronary heart disease: from the CORDIOPREV study.

MicroRNAs (miRNAs) regulate the expression of genes associated with the development of diseases, including type 2 diabetes mellitus (T2DM). However, the use of miRNAs to predict T2DM remission has been poorly studied. Therefore, we aimed to investigate whether circulating miRNAs could be used to predict the probability of T2DM remission in patients with coronary heart disease. We included the newly diagnosed T2DM (n = 190) of the 1,002 patients from the CORDIOPREV study. Seventy-three patients reverted from T2DM after 5 years of dietary intervention with a low-fat or Mediterranean diet. Plasma levels of 56 miRNAs were measured by OpenArray. Generalized linear model, receiver operating characteristic (ROC), Cox regression, and pathway analyses were performed. ROC analysis based on clinical variables showed an area under the curve (AUC) of 0.66. After a linear regression analysis, seven miRNAs were identified as the most important variables in the group's differentiation. The addition of these miRNAs to clinical variables showed an AUC of 0.79. Cox regression analysis using a T2DM remission score including miRNAs showed that high-score patients have a higher probability of T2DM remission (hazard ratio [HR]low versus high, 4.44). Finally, 26 genes involved in 10 pathways were related to the miRNAs. We have identified miRNAs (hsa-let-7b, hsa-miR-101, hsa-miR-130b-3p, hsa-miR-27a, hsa-miR-30a-5p, hsa-miR-375, and hsa-miR-486) that contribute to the prediction of T2DM remission in patients with coronary heart disease.

MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study.

BACKGROUND AND AIM: The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. METHODS: All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. RESULTS: Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. CONCLUSION: Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease. CLINICAL TRIALS NUMBER: NCT00924937.

Long-term dietary adherence and changes in dietary intake in coronary patients after intervention with a Mediterranean diet or a low-fat diet: the CORDIOPREV randomized trial.

PURPOSE: Adherence to a healthy dietary pattern positively influences clinical outcomes in cardiovascular prevention, but long-term adherence is difficult to maintain. We evaluated 5-year changes in dietary habits, adherence achieved, and its maintenance in a cohort of coronary patients from the CORDIOPREV study. METHODS: 1002 coronary patients were randomized to a Mediterranean diet (n = 502) or a low-fat diet (n = 500) and received individual-group-telephone visits and personalized dietary advice. A validated food-frequency questionnaire, a 14-point Mediterranean diet adherence screener, and a 9-point low-fat diet adherence score were used. Dietary adherence was categorized into Low, Medium, and High Adherence. Changes in nutrient intake, food consumption, and adherence were analyzed on a yearly basis. The maintenance of long-term dietary adherence was evaluated using data after the first year and fifth year. RESULTS: From baseline to 5 years, significant increases were observed in overall dietary adherence (Mediterranean diet from 8.9 to 11.4; low-fat diet from 3.9 to 7.1) and in the percentage of patients considered High Adherence (Mediterranean diet from 41 to 89%; low-fat diet from 4 to 67%). When we evaluated the maintenance of adherence, patients considered Low and Medium Adherence at 1 year increased their adherence at the 5 years with both diets and patients considered High Adherence maintained their adherence with a Mediterranean diet, but decreased their adherence with a low-fat diet. CONCLUSIONS: A comprehensive dietary intervention results in an overall long-term improvement and maintenance of adherence to the Mediterranean and low-fat diets. In our population, the Mediterranean diet group achieved a high level of adherence in the short term which was maintained in the long term.

Apolipoprotein E genetic variants interact with Mediterranean diet to modulate postprandial hypertriglyceridemia in coronary heart disease patients: CORDIOPREV study.

BACKGROUND: We try to explore whether long-term consumption of two healthy dietary patterns (low-fat [LF] diet or Mediterranean diet [MedDiet]) interacts with the apolipoprotein E (APOE) single-nucleotide polymorphisms (SNPs: rs439401, rs440446 and rs7412) modulating postprandial hypertriglyceridemia (ppHTG) in coronary heart disease (CHD) patients. METHODS AND RESULTS: We selected patients from the CORDIOPREV study with genotyping and who underwent an oral fat load test (FLT) at baseline and after 3 years follow-up (n = 506). After 3 years of follow-up, we found a gene-diet interaction between the APOE rs439401 SNP and MedDiet. Specifically, T-allele carriers in the MedDiet group showed a more significant decrease in postprandial triglycerides (TG: P = 0.03) and large triacylglycerol-rich lipoproteins (TRLs) TG (large TRLs TG; P = 0.01) compared with CC subjects. Consistently, the area under the curve of TG (AUC-TG; P-interaction = 0.03) and AUC-large TRLs TG (P-interaction = 0.02) were significantly lower in T-allele carriers compared with CC subjects. CONCLUSIONS: The long-term consumption of a MedDiet modulates ppHTG through APOE genetic variants in CHD patients. This gene-diet interaction may contribute to a more precise dietary advice in CHD patients.

Low Intake of Vitamin E Accelerates Cellular Aging in Patients With Established Cardiovascular Disease: The CORDIOPREV Study.

Leukocyte telomere length (LTL) shortening is a biomarker of cellular aging that can be decelerated by diet. We aimed to investigate the effect of dietary intake of vitamin E on biomarkers of cellular senescence in patients with established cardiovascular disease. To this end, DNA from 1,002 participants of the CORDIOPREV study (NCT00924937) was isolated and LTL was measured by real-time PCR. Dietary information was collected using a 146-item food frequency questionnaire, and several oxidative stress and damage biomarkers were determined. We found that patients with an inadequate intake of vitamin E according to the European Food Safety Authority, U.S. Food and Nutrition Board, and Spanish dietary recommendation had shorter LTL than those with an adequate intake (p = .004, p = .015, and p = .005, respectively). Moreover, we observed a positive correlation between olive oil, fish consumption and LTL (r2 = .083, p = .010; r2 = .090, p = .006, respectively). Subjects who consumed more than 30 mL olive oil/day had longer LTL than subjects with lower consumption (p = .013). Furthermore, we observed higher glutathione peroxidase activity in subjects consuming less vitamin E (p = .031). Our findings support the importance of an adequate consumption of the antioxidant vitamin E, and the value of the diet as a modulating tool of the senescence process.

Circulating miRNAs as Predictive Biomarkers of Type 2 Diabetes Mellitus Development in Coronary Heart Disease Patients from the CORDIOPREV Study.

Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers, and they may be a more sensitive way to predict development of the disease than the currently used tools. Our aim was to identify whether circulating miRNAs, added to clinical and biochemical markers, yielded better potential for predicting type 2 diabetes. The study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at baseline by qRT-PCR, and other strong biomarkers to predict diabetes were determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342) than HbA1c alone (AUC = 0.6950). The miRNA and HbA1c-based model did not improve when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI = 2.61-48.65). Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of type 2 diabetes in clinical practice.

A plasma circulating miRNAs profile predicts type 2 diabetes mellitus and prediabetes: from the CORDIOPREV study.

We aimed to explore whether changes in circulating levels of miRNAs according to type 2 diabetes mellitus (T2DM) or prediabetes status could be used as biomarkers to evaluate the risk of developing the disease. The study included 462 patients without T2DM at baseline from the CORDIOPREV trial. After a median follow-up of 60 months, 107 of the subjects developed T2DM, 30 developed prediabetes, 223 maintained prediabetes and 78 remained disease-free. Plasma levels of four miRNAs related to insulin signaling and beta-cell function were measured by RT-PCR. We analyzed the relationship between miRNAs levels and insulin signaling and release indexes at baseline and after the follow-up period. The risk of developing disease based on tertiles (T1-T2-T3) of baseline miRNAs levels was evaluated by COX analysis. Thus, we observed higher miR-150 and miR-30a-5p and lower miR-15a and miR-375 baseline levels in subjects with T2DM than in disease-free subjects. Patients with high miR-150 and miR-30a-5p baseline levels had lower disposition index (p = 0.047 and p = 0.007, respectively). The higher risk of disease was associated with high levels (T3) of miR-150 and miR-30a-5p (HRT3-T1 = 4.218 and HRT3-T1 = 2.527, respectively) and low levels (T1) of miR-15a and miR-375 (HRT1-T3 = 3.269 and HRT1-T3 = 1.604, respectively). In conclusion, our study showed that deregulated plasma levels of miR-150, miR-30a-5p, miR-15a, and miR-375 were observed years before the onset of T2DM and pre-DM and could be used to evaluate the risk of developing the disease, which may improve prediction and prevention among individuals at high risk for T2DM.

Telomerase RNA Component Genetic Variants Interact With the Mediterranean Diet Modifying the Inflammatory Status and its Relationship With Aging: CORDIOPREV Study.

Background: Leukocyte telomere length (LTL) attrition has been associated with age-related diseases. Telomerase RNA Component (TERC) genetic variants have been associated with LTL; whereas fatty acids (FAs) can interact with genetic factors and influence in aging. We explore whether variability at the TERC gene locus interacts with FA profile and two healthy diets (low-fat diet vs Mediterranean diet [MedDiet]) modulating LTL, glucose metabolism, and inflammation status in coronary heart disease (CHD) patients. Methods: Inflammation status (high-sensitivity C-reactive protein [hsCRP], glucose metabolism-glucose, insulin, and glycated hemoglobin [HbA1c], and homeostasis model assessment of insulin resistance [HOMA-IR]), LTL, FAs, and single nucleotide polymorphisms (SNPs) of the TERC gene (rs12696304, rs16847897, and rs3772190) were determined in 1,002 patients from the CORDIOPREV study (NCT00924937). Results: We report an interaction of the TERC rs12696304 SNP with monounsaturated fatty acid (MUFA) affecting LTL (p interaction = .01) and hsCRP (p interaction = .03). Among individuals with MUFA levels above the median, CC individuals showed higher LTL and lower hsCRP than G-allele carriers. Moreover, MedDiet interacted with TERC rs12696304 SNP (p interaction = .03). Specifically, CC individuals displayed a greater decrease in hsCRP than G-allele carriers. These results were not adjusted for multiple statistical testing and p less than .05 was considered significant. Conclusions: Our findings suggest that the TERC rs12696304 SNP interacts with MUFA improving inflammation status and telomere attrition related with CHD. Moreover, the MedDiet intervention improves the inflammatory profile in CC individuals compared with the G-allele carriers. These interactions could provide a right strategy for personalized nutrition in CHD patients.

Distinct features of C/N balance regulation in Prochlorococcus sp. strain MIT9313.

The abundance and significant contribution to global primary production of the marine cyanobacterium Prochlorococcus have made it one of the main models in marine ecology. Several conditions known to cause strong effects on the regulation of N-related enzymes in other cyanobacteria lacked such effect in Prochlorococcus. Prochlorococcus sp. strain MIT9313 is one of the most early-branching strains among the members of this genus. In order to further understand the C/N control system in this cyanobacterium, we studied the effect of the absence of three key elements in the ocean, namely N, P and Fe, as well as the effect of inhibitors of the N assimilation or photosynthesis on the N metabolism of this strain. Furthermore, we focused our work in the effect of ageing, as the age of cultures has clear effects on the regulation of some enzymes in Prochlorococcus. To reach this goal, expression of the main three regulators involved in N assimilation in cyanobacteria, namely ntcA, glnB and pipX, as well as that of icd (encoding for isocitrate dehydrogenase) were analysed. Our results show that the control of the main proteins involved in the C/N balance in strain MIT9313 differs from other model Prochlorococcus strains.