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Background Consumption of a Mediterranean diet, adequate levels of physical activity, and energy-restricted lifestyle interventions have been individually associated with improvements in HDL functions. Evidence of intensive interventions with calorie restriction and physical activity is, however, scarce. Objectives To determine whether an intensive lifestyle intervention with an energy-restricted Mediterranean diet plus physical activity enhanced HDL function compared to a non-hypocaloric Mediterranean eating pattern without physical activity. Methods In 391 older adults with metabolic syndrome (mean age, 65 years; mean BMI, 33.3 kg/m2) from 1 of the Prevencion con Dieta Mediterranea-Plus trial centers, we evaluated the impact of a 6-month intervention with an energy-restricted Mediterranean diet plus physical activity (intensive lifestyle; n = 190) relative to a nonrestrictive Mediterranean diet without physical activity (control; n = 201) on a set of HDL functional traits. These included cholesterol efflux capacity, HDL oxidative/inflammatory index, HDL oxidation, and levels of complement component 3, serum amyloid A, sphingosine-1-phosphate, triglycerides, and apolipoproteins A-I, A-IV, C-III, and E in apoB-depleted plasma. Results The intensive-lifestyle intervention participants displayed greater 6-month weight reductions (-3.83 kg; 95% CI: -4.57 to -3.09 kg) but no changes in HDL cholesterol compared with control-diet participants. Regarding HDL functional traits, the intensive lifestyle decreased triglyceride levels (-0.15 mg/g protein; 95% CI: -0.29 to -0.014 mg/g protein) and apoC-III (-0.11 mg/g protein; 95% CI: -0.18 to -0.026 mg/g protein) compared to the control diet, with weight loss being the essential mediator (proportions of mediation were 77.4% and 72.1% for triglycerides and apoC-III levels in HDL, respectively). Conclusions In older adults with metabolic syndrome, an energy-restricted Mediterranean diet plus physical activity improved the HDL triglyceride metabolism compared with a nonrestrictive Mediterranean diet without physical activity. This trial is registered at isrctn.com as ISRCTN89898870.

Scope: Some very-low density lipoprotein (VLDL) properties may render them more pro-atherogenic. We aimed to assess whether a Mediterranean diet (MedDiet) or an energy-reduced MedDiet with increased physical activity improves them. Methods and results: In a sample of the PREvención con DIeta MEDiterránea (PREDIMED) study, a 1-year intervention with MedDiet with extra-virgin olive oil (n = 89) or nuts (MedDiet-Nuts; n = 79) is compared with a low-fat diet (n = 90). In the PREDIMED-Plus study, a 1-year intervention with energy-reduced MedDiet and physical activity (n = 103) is compared with an ad libitum MedDiet (n = 101). VLDL levels of apolipoprotein C-I, C-III, triglycerides, and cholesterol; the apolipoprotein E-/C-I ratio; and VLDL ex-vivo triglyceride transfer are measured. In PREDIMED participants in both MedDiet groups combined, VLDL apolipoprotein C-III levels are nominally reduced (-0.023 SD units, 95% CI -0.44 to -0.014, p = 0.037). VLDL triglyceride transfer is nominally increased in the MedDiet-Nuts group (+0.39 SD units, 95% CI 0.012-0.78, p = 0.045). In PREDIMED-Plus, no inter-group differences are detected. Conclusions: In older adults at high cardiovascular risk, MedDiet is associated with lower VLDL atherogenicity versus a low-fat diet. No differences are seen after an energy-reduced MedDiet with physical activity. The authors want to thank Daniel Muñoz-Aguayo, Gemma Blanchart, and Sònia Gaixas for their laboratory support, and Stephanie Lonsdale for her help in editing the English text. A full list of names of all PREDIMED and PREDIMED-Plus study collaborators is available in the Supporting files Appendix 1. The authors also thank the PREDIMED-Plus Biobank Network as a part of the National Biobank Platform of the ISCIII for storing and managing the PREDIMED-Plus biological samples. CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of Instituto de Salud Carlos III (Madrid, Spain), and is financed by the European Regional Development Fund. Acknowledgements to European Research Council (Grant 340918). This work was supported by the Instituto de Salud Carlos III (grant numbers: IFI20/00002, PI19/00017, PI15/00047, PI18/00020, PI16/00533, PI13/00233, PI21/00024, PI20/00012, and CP21/00097) and co-funded by the European Union. The funders played no role in study design, collection, analysis, or interpretation of data, and neither in the process of writing the manuscript and the publish process.

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini&ndash, Hochberg-adjusted p-value were &gt, 1.30 and their absolute z-scores were &gt, 2.0 (&ge, 2.0 meant &ldquo, upregulation&rdquo, and &le, &minus, 2.0 &ldquo, downregulation&rdquo, ). Cancer signaling pathways were the most upregulated ones in T2D (z-score = 2.63, &minus, log(p-value) = 32.3, 88.5% (n = 906) of the total differentially expressed genes located in these pathways). In particular, integrin (z-score = 2.52, &minus, log(p-value) = 2.03) and paxillin (z-score = 2.33, &minus, log(p-value) = 1.46) signaling pathways were predicted to be upregulated, whereas the Rho guanosine diphosphate (Rho-GDP) dissociation inhibitor signaling pathway was predicted to be downregulated in T2D individuals (z-score = &minus, 2.14, &minus, log(p-value) = 2.41). Our results suggest that, at transcriptional expression level, elderly individuals with T2D present an increased activation of signaling pathways related to neoplastic processes, T-cell activation and migration, and inflammation.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvenci&oacute, n con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 &plusmn, 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (&gt, 70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) &gt, 35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

[Scope] To evaluate whether increases in the consumption of cardioprotective food groups (virgin olive oil, nuts, fruits/vegetables, legumes, whole grains, fish, and wine) are associated with improvements in high‐density lipoprotein (HDL) functions in high cardiovascular risk subjects., [Methods and Results] The association between 1‐year changes in food group consumption and HDL functionality traits in 296 high cardiovascular risk subjects is assessed. Increases in virgin olive oil (10 g d–1) and whole grain consumption (25 g d–1) are associated with increments in cholesterol efflux capacity (+0.7%, P = 0.026, and +0.6%, P = 0.017, respectively). Increases in nut (30 g d–1) and legume intake (25 g d–1) are linked to increments in paraoxonase‐1 activity (+12.2%, P = 0.049, and +11.7%, P = 0.043, respectively). Legume intake increases are also related to decreases in cholesteryl ester transfer protein activity (–4.8%, P = 0.028). Fish consumption increments (25 g d–1) are associated with increases in paraoxonase‐1 activity (+3.9%, P = 0.030) and declines in cholesteryl ester transfer protein activity (–1.6%, P = 0.021), HDL cholesterol concentrations (–1.1%, P = 0.039), and functions related to HDL levels (cholesterol efflux capacity, –1.1%, P = 0.010)., [Conclusion] Increases in the consumption of virgin olive oil, nuts, legumes, whole grains, and fish (achievable through a regular diet) were associated with improvements in HDL functions in high cardiovascular risk subjects., This work was supported by: Agència de Gestió d'Ajuts Universitaris i de Recerca (2014‐SGR‐240) and the Instituto de Salud Carlos III (CB06/03/0028, CD17/00122, CES12/025, JR14/00008, OBN17PI02, PI11/01647, and PI15/00047).

Study Objectives: To examine independent and combined associations of sleep duration and sleep variability with body composition, obesity and type 2 diabetes (T2D) in elders at high cardiovascular risk. Methods: Cross-sectional analysis of 1986 community-dwelling elders with overweight/obesity and metabolic syndrome from PREDIMEDPlus trial. Associations of accelerometry-derived sleep duration and sleep variability with body mass index (BMI), waist circumference (WC) and body composition were assessed fitting multivariable-adjusted linear regression models. Prevalence ratios (PR) and 95% confidence intervals (CI) for obesity and T2D were obtained using multivariable-adjusted Cox regression with constant time. "Bad sleepers" (age-specific non-recommended sleep duration plus sleep variability above the median) and "good sleepers" (age-specific recommended sleep duration plus sleep variability below the median) were characterized by combining sleep duration and sleep variability, and their associations with these outcomes were examined. Results: One hour/night increment in sleep duration was inversely associated with BMI (beta-0.38 kg/m(2) [95% CI -0.54, -0.23]), WC (beta-0.86 cm [95% CI -1.25, -0.47]), obesity (PR 0.96 [95% CI 0.93, 0.98]), T2D (PR 0.93 [95% CI 0.88, 0.98]) and other DXA-derived adiposity-related measurements (android fat and trunk fat, all p