Associations between the New DNA-Methylation-Based Telomere Length Estimator, the Mediterranean Diet and Genetics in a Spanish Population at High Cardiovascular Risk.

Biological aging is a relevant risk factor for chronic diseases, and several indicators for measuring this factor have been proposed, with telomere length (TL) among the most studied. Oxidative stress may regulate telomere shortening, which is implicated in the increased risk. Using a novel estimator for TL, we examined whether adherence to the Mediterranean diet (MedDiet), a highly antioxidant-rich dietary pattern, is associated with longer TL. We determined TL using DNA methylation algorithms (DNAmTL) in 414 subjects at high cardiovascular risk from Spain. Adherence to the MedDiet was assessed by a validated score, and genetic variants in candidate genes and at the genome-wide level were analyzed. We observed several significant associations (p < 0.05) between DNAmTL and candidate genes (TERT, TERF2, RTEL1, and DCAF4), contributing to the validity of DNAmTL as a biomarker in this population. Higher adherence to the MedDiet was associated with lower odds of having a shorter TL in the whole sample (OR = 0.93; 95% CI: 0.85-0.99; p = 0.049 after fully multivariate adjustment). Nevertheless, this association was stronger in women than in men. Likewise, in women, we observed a direct association between adherence to the MedDiet score and DNAmTL as a continuous variable (beta = 0.015; SE: 0.005; p = 0.003), indicating that a one-point increase in adherence was related to an average increase of 0.015 ± 0.005 kb in TL. Upon examination of specific dietary items within the global score, we found that fruits, fish, "sofrito", and whole grains exhibited the strongest associations in women. The novel score combining these items was significantly associated in the whole population. In the genome-wide association study (GWAS), we identified ten polymorphisms at the suggestive level of significance (p < 1 × 10-5) for DNAmTL (intergenics, in the IQSEC1, NCAPG2, and ABI3BP genes) and detected some gene-MedDiet modulations on DNAmTL. As this is the first study analyzing the DNAmTL estimator, genetics, and modulation by the MedDiet, more studies are needed to confirm these findings.

Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk.

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

Paradoxical Effects of Prolonged Insufficient Sleep on Lipid Profile: A Pooled Analysis of 2 Randomized Trials.

Background Insufficient sleep is associated with increased cardiovascular disease risk, but causality is unclear. We investigated the impact of prolonged mild sleep restriction (SR) on lipid and inflammatory profiles. Methods and Results Seventy-eight participants (56 women [12 postmenopausal]; age, 34.3±12.5 years; body mass index, 25.8±3.5 kg/m2) with habitual sleep duration 7 to 9 h/night (adequate sleep [AS]) underwent two 6-week conditions in a randomized crossover design: AS versus SR (AS-1.5 h/night). Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and inflammatory markers (CRP [C-reactive protein], interleukin 6, and tumor necrosis factor-α) were assessed. Linear models tested effects of SR on outcomes in the full sample and by sex+menopausal status (premenopausal versus postmenopausal women+men). In the full sample, SR increased high-density lipoprotein cholesterol compared with AS (ß=1.2±0.5 mg/dL; P=0.03). Sex+menopausal status influenced the effects of SR on change in total cholesterol (P-interaction=0.04), LDL-C (P-interaction=0.03), and interleukin 6 (P-interaction=0.07). Total cholesterol and LDL-C decreased in SR versus AS in premenopausal women (total cholesterol: ß=-4.2±1.9 mg/dL; P=0.03; LDL-C: ß=-6.3±2.0 mg/dL; P=0.002). Given paradoxical effects of SR on cholesterol concentrations, we explored associations between changes in inflammation and end point lipids under each condition. Increases in interleukin 6 and tumor necrosis factor-α during SR tended to relate to lower LDL-C in premenopausal women (interleukin 6: ß=-5.3±2.6 mg/dL; P=0.051; tumor necrosis factor-α: ß=-32.8±14.2 mg/dL; P=0.027). Conclusions Among healthy adults, prolonged insufficient sleep does not increase atherogenic lipids. However, increased inflammation in SR tends to predict lower LDL-C in premenopausal women, resembling the "lipid paradox" in which low cholesterol associates with increased cardiovascular disease risk in proinflammatory conditions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02835261, NCT02960776.

Metabolic syndrome criteria and severity and carbon dioxide (CO2) emissions in an adult population.

BACKGROUND: Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet. AIMS: To assess the association between MetS severity and amount of carbon dioxide (CO2) emitted in an adult population. DESIGN: Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS). METHODS: Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score. RESULTS: Higher glycaemia levels were found in people with higher CO2 emissions. The risk of having high severe MetS was related to high CO2 emissions. CONCLUSIONS: Low CO2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet. TRIAL REGISTRATION: ISRCTN, ISRCTN89898870 . Registered 05 September 2013.

Changes in eating patterns in response to chronic insufficient sleep and their associations with diet quality: a randomized trial.

STUDY OBJECTIVES: Insufficient sleep leads to overconsumption, but the factors contributing to this effect are poorly understood. Therefore, we assessed the influence of prolonged curtailment of sleep on free-living eating patterns linked with overconsumption and explored associations of these eating patterns with diet quality under different sleep conditions. METHODS: Sixty-five adults (47 females) participated in outpatient randomized crossover studies with two 6-week conditions: adequate sleep (7-9 h/night) and sleep restriction (-1.5 h/night relative to screening). Food records were collected over 3 nonconsecutive days, from which we ascertained data on eating frequency, midpoint, and window and intakes of energy and nutrients. Linear mixed models were used to assess the impact of sleep condition on change in eating pattern (sleep × week interaction) and the relation between eating patterns and dietary intakes (sleep × eating pattern interaction). RESULTS: Sleep condition impacted the change in eating frequency across weeks, with eating frequency increasing in sleep restriction relative to adequate sleep (ß = 0.3 ± 0.1; P = .046). Across conditions, eating more frequently tended to relate to higher energy intakes (ß = 60.5 ± 34.6; P = .082). Sleep also influenced the relation of variability in eating midpoint with intakes of saturated fat (ß = 6.0 ± 2.1; P = .005), polyunsaturated fat (ß = -3.9 ± 2.0; P = .051), and added sugar (ß = 17.3 ± 6.2; P = .006), with greater midpoint variability associated with more adverse changes in these diet quality components in sleep restriction vs adequate sleep. CONCLUSIONS: Chronic short sleep increases eating frequency and adversely influences associations of variability in meal timing with components of diet quality. These findings help to explain how short sleep leads to overconsumption and obesity. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Impact of Sleep Restriction in Women; URL: https://clinicaltrials.gov/ct2/show/NCT02835261; Identifier: NCT02835261 and Name: Impact of Sleep Restriction on Performance in Adults; URL: https://clinicaltrials.gov/ct2/show/NCT02960776; Identifier: NCT02960776. CITATION: Barragán R, Zuraikat FM, Tam V, RoyChoudhury A, St-Onge M-P. Changes in eating patterns in response to chronic insufficient sleep and their associations with diet quality: a randomized trial. J Clin Sleep Med. 2023;19(11):1867-1875.

Timing of Meals and Sleep in the Mediterranean Population: The Effect of Taste, Genetics, Environmental Determinants, and Interactions on Obesity Phenotypes.

Circadian rhythms regulate the sleep-wake and feeding-fasting cycles. Sleep and feeding constitute a complex cycle that is determined by several factors. Despite the importance of sleep duration and mealtimes for many obesity phenotypes, most studies on dietary patterns have not investigated the contribution of these variables to the phenotypes analyzed. Likewise, they have not investigated the factors related to sleep or mealtimes. Thus, our aims were to investigate the link between taste perception and eating/sleep patterns and to analyze the effect of the interactions between sleep/meal patterns and genetic factors on obesity phenotypes. We conducted a cross-sectional analysis on 412 adults from the Mediterranean population. We measured taste perception (bitter, sweet, salty, sour, and umami) and assessed sleep duration and waketime. The midpoint of sleep and social jetlag was computed. From the self-reported timing of meals, we estimated the eating window, eating midpoint, and eating jetlag. Adherence to the Mediterranean diet was measured with a validated score. Selected polymorphisms in the TAS2R38, CLOCK, and FTO genes were determined, and their associations and interactions with relevant phenotypes were analyzed. We found various associations between temporal eating, sleep patterns, and taste perception. A higher bitter taste perception was associated with an earlier eating midpoint (p = 0.001), breakfast time (p = 0.043), dinner time (p = 0.009), waketime (p < 0.001), and midpoint of sleep (p = 0.009). Similar results were observed for the bitter taste polymorphism TAS2R38-rs713598, a genetic instrumental variable for bitter perception, increasing the causality of the associations. Moreover, significant gene-sleep interactions were detected between the midpoint of sleep and the TAS2R38-rs713598 (p = 0.032), FTO-rs9939609 (p = 0.037), and CLOCK-rs4580704 (p = 0.004) polymorphisms which played a role in determining obesity phenotypes. In conclusion, our study provided more information on the sleep and mealtime patterns of the general Spanish Mediterranean population than on their main relationships. Moreover, we were able to show significant associations between taste perception, specifically bitter taste; sleep time; and mealtimes as well as an interaction between sleep time and several genetic variants linked to obesity phenotypes. However, additional research is needed to better characterize the causality and mechanisms behind these associations.

Single and Combined Associations of Plasma and Urine Essential Trace Elements (Zn, Cu, Se, and Mn) with Cardiovascular Risk Factors in a Mediterranean Population.

Trace elements are micronutrients that are required in very small quantities through diet but are crucial for the prevention of acute and chronic diseases. Despite the fact that initial studies demonstrated inverse associations between some of the most important essential trace elements (Zn, Cu, Se, and Mn) and cardiovascular disease, several recent studies have reported a direct association with cardiovascular risk factors due to the fact that these elements can act as both antioxidants and pro-oxidants, depending on several factors. This study aims to investigate the association between plasma and urine concentrations of trace elements and cardiovascular risk factors in a general population from the Mediterranean region, including 484 men and women aged 18−80 years and considering trace elements individually and as joint exposure. Zn, Cu, Se, and Mn were determined in plasma and urine using an inductively coupled plasma mass spectrometer (ICP-MS). Single and combined analysis of trace elements with plasma lipid, blood pressure, diabetes, and anthropometric variables was undertaken. Principal component analysis, quantile-based g-computation, and calculation of trace element risk scores (TERS) were used for the combined analyses. Models were adjusted for covariates. In single trace element models, we found statistically significant associations between plasma Se and increased total cholesterol and systolic blood pressure; plasma Cu and increased triglycerides and body mass index; and urine Zn and increased glucose. Moreover, in the joint exposure analysis using quantile g-computation and TERS, the combined plasma levels of Zn, Cu, Se (directly), and Mn (inversely) were strongly associated with hypercholesterolemia (OR: 2.03; 95%CI: 1.37−2.99; p < 0.001 per quartile increase in the g-computation approach). The analysis of urine mixtures revealed a significant relationship with both fasting glucose and diabetes (OR: 1.91; 95%CI: 1.01−3.04; p = 0.046). In conclusion, in this Mediterranean population, the combined effect of higher plasma trace element levels (primarily Se, Cu, and Zn) was directly associated with elevated plasma lipids, whereas the mixture effect in urine was primarily associated with plasma glucose. Both parameters are relevant cardiovascular risk factors, and increased trace element exposures should be considered with caution.

Longitudinal association of dietary acid load with kidney function decline in an older adult population with metabolic syndrome.

Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR). Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR (n = 5,874) or UACR (n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase. Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, ß: -0.64 ml/min/1.73 m2; 95% CI: -1.21 to -0.08 and NEAP, ß: -0.56 ml/min/1.73 m2; 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load. Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome.

Circulating carotenoids are associated with favorable lipid and fatty acid profiles in an older population at high cardiovascular risk.

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [-2.79 mg/dl (95% CI: -4.25, -1.34) and -5.15 mg/dl (95% CI: -7.38, -2.93), p-values = 0.0002 and <0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [-0.09% (95% CI: -0.14, -0.03) and -0.15 % (95% CI: -0.23, -0.08), p-values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: -0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p-values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p-value: 0.0002], and lower fasting plasma glucose in men [-1.35 mg/dl (95% CI: -2.12, -0.59), p-value: 0.001].

Association Among Polyphenol Intake, Uric Acid, and Hyperuricemia: A Cross-Sectional Analysis in a Population at High Cardiovascular Risk.

Background Dietary polyphenol intake has been associated with a decreased risk of hyperuricemia, but most of this knowledge comes from preclinical studies. The aim of the present study was to assess the association of the intake of different classes of polyphenols with serum uric acid and hyperuricemia. Methods and Results This cross-sectional analysis involved baseline data of 6332 participants. Food polyphenol content was estimated by a validated semiquantitative food frequency questionnaire and from the Phenol-Explorer database. Multivariable-adjusted linear regression models with serum uric acid (milligrams per deciliter) as the outcome and polyphenol intake (quintiles) as the main independent variable were fitted. Cox regression models with constant follow-up time (t=1) were performed to estimate the prevalence ratios (PRs) of hyperuricemia (≥7 mg/dL in men and ≥6 mg/dL in women). An inverse association between the intake of the phenolic acid class (ß coefficient, -0.17 mg/dL for quintile 5 versus quintile 1 [95% CI, -0.27 to -0.06]) and hydroxycinnamic acids (ß coefficient, -0.19 [95% CI, -0.3 to -0.09]), alkylmethoxyphenols (ß coefficient, -0.2 [95% CI, -0.31 to -0.1]), and methoxyphenols (ß coefficient, -0.24 [95% CI, -0.34 to -0.13]) subclasses with serum uric acid levels and hyperuricemia (PR, 0.82 [95% CI, 0.71-0.95]; PR, 0.82 [95% CI, 0.71-0.95]; PR, 0.80 [95% CI, 0.70-0.92]; and PR, 0.79 [95% CI, 0.69-0.91]; respectively) was found. The intake of hydroxybenzoic acids was directly and significantly associated with mean serum uric acid levels (ß coefficient, 0.14 for quintile 5 versus quintile 1 [95% CI, 0.02-0.26]) but not with hyperuricemia. Conclusions In individuals with metabolic syndrome, a higher intake of some polyphenol subclasses (hydroxycinnamic acids, alkylmethoxyphenol, and methoxyphenol) was inversely associated with serum uric acid levels and hyperuricemia. Nevertheless, our findings warrant further research.

Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population.

Background and Objectives: The gut microbiota has been increasingly recognized as a relevant factor associated with metabolic diseases. However, directly measuring the microbiota composition is a limiting factor for several studies. Therefore, using genetic variables as proxies for the microbiota composition is an important issue. Landmark microbiome-host genome-wide association studies (mbGWAS) have identified many SNPs associated with gut microbiota. Our aim was to analyze the association between relevant microbiome-related genetic variants (Mi-RSNPs) and fasting glucose and type 2 diabetes in a Mediterranean population, exploring the interaction with Mediterranean diet adherence. Materials and Methods: We performed a cross-sectional study in a high-cardiovascular-risk Mediterranean population (n = 1020), analyzing the association of Mi-RSNPs (from four published mbGWAS) with fasting glucose and type 2 diabetes. A single-variant approach was used for fitting fasting glucose and type 2 diabetes to a multivariable regression model. In addition, a Mendelian randomization analysis with multiple variants was performed as a sub-study. Results: We obtained several associations between Mi-RSNPs and fasting plasma glucose involving gut Gammaproteobacteria_HB, the order Rhizobiales, the genus Rumminococcus torques group, and the genus Tyzzerella as the top ranked. For type 2 diabetes, we also detected significant associations with Mi-RSNPs related to the order Rhizobiales, the family Desulfovibrionaceae, and the genus Romboutsia. In addition, some Mi-RSNPs and adherence to Mediterranean diet interactions were detected. Lastly, the formal Mendelian randomization analysis suggested combined effects. Conclusions: Although the use of Mi-RSNPs as proxies of the microbiome is still in its infancy, and although this is the first study analyzing such associations with fasting plasma glucose and type 2 diabetes in a Mediterranean population, some interesting associations, as well as modulations, with adherence to the Mediterranean diet were detected in these high-cardiovascular-risk subjects, eliciting new hypotheses.

Influence of DNA-Polymorphisms in Selected Circadian Clock Genes on Clock Gene Expression in Subjects from the General Population and Their Association with Sleep Duration.

Background and Objectives: Circadian rhythms have an important implication in numerous physiological and metabolic processes, including the sleep/wake cycle. Inter-individual differences in factors associated with circadian system may be due to gene differences in gene expression. Although several studies have analyzed the association between DNA polymorphisms and circadian variables, the influence on gene expression has been poorly analyzed. Our goal was to analyze the association of genetic variations in the clock genes and the gene expression level. Materials and Methods: We carried out a cross-sectional study of 102 adults (50.9% women). RNA and DNA were isolated from blood and single-nucleotide polymorphisms (SNPs), and the main circadian clock genes were determined. Gene expression of CLOCK, PER1, and VRK2 genes was measured by Reverse-transcription polymerase chain reaction (RT-PCR). The association between the DNA-SNPs and gene expression was analyzed at the gene level. In addition, a polygenic risk score (PRS), including all the significant SNPs related to gene expression, was created for each gene. Multivariable model analysis was performed. Results: Sex-specific differences were detected in PER1 expression, with these being higher in women (p = 0.034). No significant differences were detected in clock genes expression and lifestyle variables. We observed a significant association between the ARNTL-rs7924734, ARNTL-rs10832027, VRK2- rs2678902 SNPs, and CLOCK gene expression; the PER3-rs228642 and PER3-rs10127838 were related to PER1 expression, and the ARNTL-rs10832027, ARNTL-rs11022778, and MNTR1B-rs10830963 were associated with VRK2 gene expression (p < 0.05). The specific PRS created was significantly associated with each of the gene expressions analyzed (p < 0.001). Finally, sleep duration was associated with PER3-rs238666 (p = 0.008) and CLOCK-rs4580704 (p = 0.023). Conclusion: We detected significant associations between DNA-SNPs in the clock genes and their gene expression level in leukocytes and observed some differences in gene expression per sex. Moreover, we reported for the first time an association between clock gene polymorphisms and CLOCK, PER1, and VRK2 gene expression. These findings need further investigation.

Associations Between the Modified Food Standard Agency Nutrient Profiling System Dietary Index and Cardiovascular Risk Factors in an Elderly Population.

Background: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm-NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure. Materials and Methods: Dietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55-75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models. Results: Compared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (ß coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; <0.001; 6.27 [2.46, 10.09]; <0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60]; <0.001; 1.19 [0.89, 1.50]; <0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown. Conclusion: This prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure.

Adopting a High-Polyphenolic Diet Is Associated with an Improved Glucose Profile: Prospective Analysis within the PREDIMED-Plus Trial.

Previous studies suggested that dietary polyphenols could reduce the incidence and complications of type-2 diabetes (T2D); although the evidence is still limited and inconsistent. This work analyzes whether changing to a diet with a higher polyphenolic content is associated with an improved glucose profile. At baseline, and at 1 year of follow-up visits, 5921 participants (mean age 65.0 ± 4.9, 48.2% women) who had overweight/obesity and metabolic syndrome filled out a validated 143-item semi-quantitative food frequency questionnaire (FFQ), from which polyphenol intakes were calculated. Energy-adjusted total polyphenols and subclasses were categorized in tertiles of changes. Linear mixed-effect models with random intercepts (the recruitment centers) were used to assess associations between changes in polyphenol subclasses intake and 1-year plasma glucose or glycosylated hemoglobin (HbA1c) levels. Increments in total polyphenol intake and some classes were inversely associated with better glucose levels and HbA1c after one year of follow-up. These associations were modified when the analyses were run considering diabetes status separately. To our knowledge, this is the first study to assess the relationship between changes in the intake of all polyphenolic groups and T2D-related parameters in a senior population with T2D or at high-risk of developing T2D.

Sleep and Diet: Mounting Evidence of a Cyclical Relationship.

Two factors intrinsic to health are diet and sleep. These two behaviors may well influence one another. Indeed, that insufficient sleep adversely impacts dietary intakes is well documented. On the other hand, diet may influence sleep via melatonin and its biosynthesis from tryptophan. Experimental data exist indicating that provision of specific foods rich in tryptophan or melatonin can improve sleep quality. Whole diets rich in fruits, vegetables, legumes, and other sources of dietary tryptophan and melatonin have been shown to predict favorable sleep outcomes. Although clinical trials are needed to confirm a causal impact of dietary patterns on sleep and elucidate underlying mechanisms, available data illustrate a cyclical relation between these lifestyle factors. We recommend adopting a healthful diet to improve sleep, which may further promote sustained favorable dietary practices.

A molecular signature for the metabolic syndrome by urine metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a multimorbid long-term condition without consensual medical definition and a diagnostic based on compatible symptomatology. Here we have investigated the molecular signature of MetS in urine. METHODS: We used NMR-based metabolomics to investigate a European cohort including urine samples from 11,754 individuals (18-75 years old, 41% females), designed to populate all the intermediate conditions in MetS, from subjects without any risk factor up to individuals with developed MetS (4-5%, depending on the definition). A set of quantified metabolites were integrated from the urine spectra to obtain metabolic models (one for each definition), to discriminate between individuals with MetS. RESULTS: MetS progression produces a continuous and monotonic variation of the urine metabolome, characterized by up- or down-regulation of the pertinent metabolites (17 in total, including glucose, lipids, aromatic amino acids, salicyluric acid, maltitol, trimethylamine N-oxide, and p-cresol sulfate) with some of the metabolites associated to MetS for the first time. This metabolic signature, based solely on information extracted from the urine spectrum, adds a molecular dimension to MetS definition and it was used to generate models that can identify subjects with MetS (AUROC values between 0.83 and 0.87). This signature is particularly suitable to add meaning to the conditions that are in the interface between healthy subjects and MetS patients. Aging and non-alcoholic fatty liver disease are also risk factors that may enhance MetS probability, but they do not directly interfere with the metabolic discrimination of the syndrome. CONCLUSIONS: Urine metabolomics, studied by NMR spectroscopy, unravelled a set of metabolites that concomitantly evolve with MetS progression, that were used to derive and validate a molecular definition of MetS and to discriminate the conditions that are in the interface between healthy individuals and the metabolic syndrome.

Data-Driven Clustering Approach to Derive Taste Perception Profiles from Sweet, Salt, Sour, Bitter, and Umami Perception Scores: An Illustration among Older Adults with Metabolic Syndrome.

BACKGROUND: Current approaches to studying relations between taste perception and diet quality typically consider each taste-sweet, salt, sour, bitter, umami-separately or aggregately, as total taste scores. Consistent with studying dietary patterns rather than single foods or total energy, an additional approach may be to study all 5 tastes collectively as "taste perception profiles." OBJECTIVE: We developed a data-driven clustering approach to derive taste perception profiles from taste perception scores and examined whether profiles outperformed total taste scores for capturing individual variability in taste perception. METHODS: The cohort included 367 community-dwelling adults [55-75 y; 55% female; BMI (kg/m2): 32.2 ± 3.6] with metabolic syndrome from PREDIMED-Plus, Valencia. Cluster analysis identified subgroups of individuals with similar patterns in taste perception (taste perception profiles); quantitative criteria were used to select the cluster algorithm, determine the optimal number of clusters, and assess the profiles' validity and stability. Goodness-of-fit parameters from adjusted linear regression evaluated the individual variability captured by each approach. RESULTS: A k-means algorithm with 6 clusters best fit the data and identified the following taste perception profiles: Low All, High Bitter, High Umami, Low Bitter & Umami, High All But Bitter and High All But Umami. All profiles were valid and stable. Compared with total taste scores, taste perception profiles explained more variability in bitter and umami perception (adjusted R2: 0.19 vs. 0.63, respectively; 0.40 vs. 0.65, respectively) and were comparable for sweet, salt, and sour. In addition, taste perception profiles captured differential perceptions of each taste within individuals, whereas these patterns were lost with total taste scores. CONCLUSIONS: Among older adults with metabolic syndrome, taste perception profiles derived via data-driven clustering may provide a valuable approach to capture individual variability in perception of all 5 tastes and their collective influence on diet quality. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870.

Actigraphy-Derived Sleep Is Associated with Eating Behavior Characteristics.

Poor sleep is a determinant of obesity, with overconsumption of energy contributing to this relationship. Eating behavior characteristics are predictive of energy intake and weight change and may underlie observed associations of sleep with weight status and obesity risk factors. However, relationships between sleep and dimensions of eating behavior, as well as possible individual differences in these relations, are not well characterized. Therefore, the aim of this study was to evaluate whether sleep behaviors, including duration, timing, quality, and regularity relate to dietary restraint, disinhibition, and tendency towards hunger and to explore whether these associations differ by sex. This cross-sectional study included 179 adults aged 20-73 years (68.7% women, 64.8% with BMI ≥ 25 kg/m2). Sleep was evaluated by accelerometry over 2 weeks. Eating behavior dimensions were measured with the Three-Factor Eating Questionnaire. Prolonged wake after sleep onset (WASO) (0.029 ± 0.011, p = 0.007), greater sleep fragmentation index (0.074 ± 0.036, p = 0.041), and lower sleep efficiency (-0.133 ± 0.051, p = 0.010) were associated with higher dietary restraint. However, higher restraint attenuated associations of higher WASO and sleep fragmentation with higher BMI (p-interactions < 0.10). In terms of individual differences, sex influenced associations of sleep quality measures with tendency towards hunger (p-interactions < 0.10). Stratified analyses showed that, in men only, higher sleep fragmentation index, longer sleep onset latency, and lower sleep efficiency were associated with greater tendency towards hunger (ß = 0.115 ± 0.037, p = 0.003, ß = 0.169 ± 0.072, p = 0.023, ß = -0.150 ± 0.055, p = 0.009, respectively). Results of this analysis suggest that the association of poor sleep on food intake could be exacerbated in those with eating behavior traits that predispose to overeating, and this sleep-eating behavior relation may be sex-dependent. Strategies to counter overconsumption in the context of poor quality sleep should be evaluated in light of eating behavior traits.

Circulating Adiponectin and Its Association with Metabolic Traits and Type 2 Diabetes: Gene-Diet Interactions Focusing on Selected Gene Variants and at the Genome-Wide Level in High-Cardiovascular Risk Mediterranean Subjects.

Adiponectin is gaining renewed interest since, in addition to its possible protective role against insulin resistance and arteriosclerosis, recent studies suggest other additional favorable effects. However, the influence of gene-diet interactions on plasma adiponectin levels is still little understood. We analyzed the association between plasma adiponectin levels and various metabolic traits in a high-cardiovascular risk Mediterranean population, as well as the genetic effect of four candidate single-nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and their interactions with the Mediterranean dietary pattern. Additionally, we explored, at the genome-wide level, the SNPs most associated with plasma adiponectin levels, as well as gene-diet interactions with the Mediterranean diet. In the 954 participants studied (aged 55-80 years), plasma adiponectin levels were strongly associated with plasma HDL-C concentrations (p = 6.6 × 10-36) and inversely related to triglycerides (p = 4.7 × 10-18), fasting glucose (p = 3.5 × 10-16) and type 2 diabetes (p = 1.4 × 10-7). Of the four pre-selected ADIPOQ candidate SNPs, the one most associated with plasma adiponectin was the -11391G > A (rs17300539) promoter SNP (p = 7.2 × 10-5, in the multivariable adjusted model). No significant interactions with the Mediterranean diet pattern were observed for these SNPs. Additionally, in the exploratory genome-wide association study (GWAS), we found new SNPs associated with adiponectin concentrations at the suggestive genome-wide level (p < 1 × 10-5) for the whole population, including the lead SNP rs9738548 (intergenic) and rs11647294 in the VAT1L (Vesicle Amine Transport 1 Like) gene. We also found other promising SNPs on exploring different strata such as men, women, diabetics and non-diabetics (p = 3.5 × 10-8 for rs2850066). Similarly, we explored gene-Mediterranean diet interactions at the GWAS level and identified several SNPs with gene-diet interactions at p < 1 × 10-5. A remarkable gene-diet interaction was revealed for the rs2917570 SNP in the OPCML (Opioid Binding Protein/Cell Adhesion Molecule Like) gene, previously reported to be associated with adiponectin levels in some populations. Our results suggest that, in this high-cardiovascular risk Mediterranean population, and even though adiponectin is favorably associated with metabolic traits and lower type 2 diabetes, the gene variants more associated with adiponectin may be population-specific, and some suggestive gene-Mediterranean diet interactions were detected.

Association between ankle-brachial index and cognitive function in participants in the PREDIMED-Plus study: cross-sectional assessment.

INTRODUCTION AND OBJECTIVES: The ankle-brachial index (ABI) is an indicator of peripheral artery disease (PAD). The aim of this study was to assess the association between PAD, measured with the ABI, and cognitive function in persons with overweight or obesity and metabolic syndrome. METHODS: Cross-sectional study conducted with baseline data from the PREDIMED-Plus study, which included 4898 participants (after exclusion of those without ABI measurements) aged between 55 and 75 years, and with overweight or obesity and metabolic syndrome. At the baseline assessment, we measured the ABI with a standardized protocol and assessed the presence of other cardiovascular risk factors (eg, diabetes, dyslipidemia, hypertension). Cognitive function was evaluated using several tests validated for the Spanish population (mini-mental state examination [MMSE], phonological and semantic verbal fluency test, WAIS-III working memory index [WMI], parts A and B of the trail making test (TMT), and clock drawing test). Generalized linear models were used to assess the association between the ABI and cognitive function. RESULTS: Among the participants, 3.4% had PAD defined as ABI ≤ 0.9, and 3.3% had arterial calcification defined as ABI ≥ 1.4. PAD was associated with age, systolic blood pressure and obesity indicators, while arterial calcification was also associated with obesity and diabetes. No significant associations were observed between cognitive function and ABI or PAD. CONCLUSIONS: In our sample, the presence of PAD increased with age, blood pressure, and obesity. No significant association was observed between ABI, PAD, or cognitive function.