Integrative development of a short screening questionnaire of highly processed food consumption (sQ-HPF).

BACKGROUND: Recent lifestyle changes include increased consumption of highly processed foods (HPF), which has been associated with an increased risk of non-communicable diseases (NCDs). However, nutritional information relies on the estimation of HPF consumption from food-frequency questionnaires (FFQ) that are not explicitly developed for this purpose. We aimed to develop a short screening questionnaire of HPF consumption (sQ-HPF) that integrates criteria from the existing food classification systems. METHODS: Data from 4400 participants (48.1% female and 51.9% male, 64.9 ± 4.9 years) of the Spanish PREDIMED-Plus ("PREvention with MEDiterranean DIet") trial were used for this analysis. Items from the FFQ were classified according to four main food processing-based classification systems (NOVA, IARC, IFIC and UNC). Participants were classified into tertiles of HPF consumption according to each system. Using binomial logistic regression, food groups associated with agreement in the highest tertile for at least two classification systems were chosen as items for the questionnaire. ROC analysis was used to determine cut-off points for the frequency of consumption of each item, from which a score was calculated. Internal consistency of the questionnaire was assessed through exploratory factor analysis (EFA) and Cronbach's analysis, and agreement with the four classifications was assessed with weighted kappa coefficients. RESULTS: Regression analysis identified 14 food groups (items) associated with high HPF consumption for at least two classification systems. EFA showed that items were representative contributors of a single underlying factor, the "HPF dietary pattern" (factor loadings around 0.2). We constructed a questionnaire asking about the frequency of consumption of those items. The threshold frequency of consumption was selected using ROC analysis. Comparison of the four classification systems and the sQ-HPF showed a fair to high agreement. Significant changes in lifestyle characteristics were detected across tertiles of the sQ-HPF score. Longitudinal changes in HPF consumption were also detected by the sQ-HPF, concordantly with existing classification systems. CONCLUSIONS: We developed a practical tool to measure HPF consumption, the sQ-HPF. This may be a valuable instrument to study its relationship with NCDs. TRIAL REGISTRATION: Retrospectively registered at the International Standard Randomized Controlled Trial Registry ( ISRCTN89898870 ) on July 24, 2014.

Association between the Prime Diet Quality Score and depressive symptoms in a Mediterranean population with metabolic syndrome. Cross-sectional and 2-year follow-up assessment from PREDIMED-PLUS study.

The burden of depression is increasing worldwide, specifically in older adults. Unhealthy dietary patterns may partly explain this phenomenon. In the Spanish PREDIMED-Plus study, we explored (1) the cross-sectional association between the adherence to the Prime Diet Quality Score (PDQS), an a priori-defined high-quality food pattern, and the prevalence of depressive symptoms at baseline (cross-sectional analysis) and (2) the prospective association of baseline PDQS with changes in depressive symptomatology after 2 years of follow-up. After exclusions, we assessed 6612 participants in the cross-sectional analysis and 5523 participants in the prospective analysis. An energy-adjusted high-quality dietary score (PDQS) was assessed using a validated FFQ. The cross-sectional association between PDQS and the prevalence of depression or presence of depressive symptoms and the prospective changes in depressive symptoms were evaluated through multivariable regression models (logistic and linear models and mixed linear-effects models). PDQS was inversely associated with depressive status in the cross-sectional analysis. Participants in the highest quintile of PDQS (Q5) showed a significantly reduced odds of depression prevalence as compared to participants in the lowest quartile of PDQS (Q1) (OR (95 %) CI = 0·82 (0·68, 0·98))). The baseline prevalence of depression decreased across PDQS quintiles (Pfor trend = 0·015). A statistically significant association between PDQS and changes in depressive symptoms after 2-years follow-up was found (ß (95 %) CI = -0·67 z-score (-1·17, -0·18). A higher PDQS was cross-sectionally related to a lower depressive status. Nevertheless, the null finding in our prospective analysis raises the possibility of reverse causality. Further prospective investigation is required to ascertain the association between PDQS and changes in depressive symptoms along time.

Inflammatory potential of diet and bone mineral density in a senior Mediterranean population: a cross-sectional analysis of PREDIMED-Plus study.

PURPOSE: Inflammation could play a key role in tissue damage and bone metabolism. The modified dietary inflammatory score (M-DIS) is a validated tool to estimate the inflammatory potential of the diet. In the present study, we evaluate the associations between the M-DIS and bone mineral density (BMD) in a senior Mediterranean population with overweight/obesity and metabolic syndrome. METHODS: Baseline cross-sectional association between the M-DIS and bone mineral density was assessed in 1134 participants of the multicenter PREDIMED-Plus trial (aged 55-75 with overweight/obesity and metabolic syndrome). BMD was measured using Dual-energy X-ray Absorptiometry scans and participants answered a food frequency questionnaire to determine the M-DIS. BMD was categorized as low BMD when T score was equal or lower than -1 and normal BMD in another case. Associations between BMD and M-DIS were evaluated by using linear and logistic regressions adjusted by other co-variates. RESULTS: Participants in the top tertile of the M-DIS had a lower BMD at total femur [ß (95% CI) - 0.02 (- 0.04, - 0.01)], trochanter areas [ß (95% CI) - 0.03 (- 0.05, - 0.01)] and lumbar spine area [ß (95% CI) - 0.03 (- 0.07, 0.01)] (but in the last case, measures were less precise and hence not statistically significant) compared to those in the lower M-DIS tertile. Multiple logistic regression analyses showed that the odds of the total femur and femoral trochanter osteopenia/osteoporosis were higher in participants in the top tertile compared to those in the lowest tertile of M-DIS [OR (95% CI) 1.71 (1.12, 2.64), P for trend 0.015; 2.02 (1.29, 3.21), P for trend 0.002, respectively]. CONCLUSION: A high pro-inflammatory diet, measured by the M-DIS, is associated with lower BMD in a senior Mediterranean population with metabolic syndrome.

Vitamin K dietary intake is associated with cognitive function in an older adult Mediterranean population.

BACKGROUND: In the last years, evidence that dietary vitamin K could have a role in the cognitive domain has increased. However, data from large trials are limited. The objective of this study was to assess the association of 2 year changes in the dietary intake of vitamin K with cognitive function measured through neuropsychological performance tests. METHODS: In 5,533 participants of the multicentre PREDIMED-Plus study (48.1% women, age 65.1 ± 4.9 years with overweight/obesity and metabolic syndrome), we assessed the adjusted odds ratios of cognitive function decline according to 2 year changes in vitamin K intake. Participants answered a battery of cognitive function tests and Food Frequency Questionnaires (FFQs) in order to estimate the vitamin K dietary intake. RESULTS: After adjusting for potential cofounders, the highest tertile of change of dietary vitamin K intake (median [IQR]; 194.4 µg/d [120.9, 373.1]) was inversely associated with a Mini-Mental State Examination (MMSE) score ≤24 (OR [95% CI]; 0.53 [0.35, 0.79] P for trend = 0.002) compared with a decrease in the intake of vitamin K (median [IQR]; -97.8 µg/d [-292.8, -51.5]). A significant positive association between changes in dietary vitamin K intake and the semantic verbal fluency test scores (OR [95% CI]; 0.69 [0.51, 0.94] P for trend = 0.019) was found. CONCLUSIONS: An increase of the intake of dietary vitamin K was associated with better cognitive function scores, independently of recognised risk factors for cognitive decline, in an older adult Mediterranean population with high cardiovascular risk.

Targeting body composition in an older population: do changes in movement behaviours matter? Longitudinal analyses in the PREDIMED-Plus trial.

BACKGROUND: The optimal distribution between physical activity (PA) levels and sedentary behaviour (SB) for the greatest benefits for body composition among older adults with overweight/obesity and chronic health conditions remains unclear. We aimed to determine the prospective association between changes in PA and in SB with concurrent changes in body composition and to examine whether reallocating inactive time into different physical activity levels was associated with 12-month change to body composition in older adults. METHODS: Longitudinal assessment nested in the PREDIMED-Plus trial. A subsample (n = 1564) of men and women (age 55-75 years) with overweight/obesity and metabolic syndrome from both arms of the PREDIMED-Plus trial was included in the present analysis. Participants were followed up at 6 and 12 months. Physical activity and SB were assessed using validated questionnaires. Out of 1564 participants, 388 wore an accelerometer to objectively measure inactive time and PA over a 7-day period. At each time point, participants' body composition was measured using dual-energy X-ray absorptiometry (DXA). Standard covariate-adjusted and isotemporal substitution modelling were applied to linear mixed-effects models. RESULTS: Increasing 30 min of total PA and moderate-to-vigorous physical activity (MVPA) was associated with significant reductions in body fat (ß - 0.07% and - 0.08%) and visceral adipose tissue (VAT) (- 13.9 g, and - 15.6 g) at 12 months (all p values < 0.001). Reallocating 30 min of inactive time to MVPA was associated with reductions in body fat and VAT and with an increase in muscle mass and muscle-to-fat mass ratio (all p values < 0.001). CONCLUSIONS: At 12 months, increasing total PA and MVPA and reducing total SB and TV-viewing SB were associated with improved body composition in participants with overweight or obesity, and metabolic syndrome. This was also observed when substituting 30 min of inactive time with total PA, LPA and MVPA, with the greatest benefits observed with MVPA. TRIAL REGISTRATION: International Standard Randomized Controlled Trial (ISRCTN), 89898870 . Retrospectively registered on 24 July 2014.

CUN-BAE Index as a Screening Tool to Identify Increased Metabolic Risk in Apparently Healthy Normal-Weight Adults and Those with Obesity.

BACKGROUND: Imbalanced dietary intake is related to increased adiposity, which is linked to increased metabolic risk even in the absence of obesity. BMI is traditionally used to classify body fatness and weight range, but it only considers body weight and height. The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) equation has appeared as an additional tool to estimate adiposity considering also other relevant parameters, i.e., sex and age. OBJECTIVES: We aimed to determine whether the CUN-BAE index could estimate adiposity-related metabolic risk in apparently healthy, normoglycemic adults. METHODS: In this case-control study, men and women (18-45 y old) were classified as normal-weight (NW) [n = 20; BMI (in kg/m2) <25] or overweight-obese (OW-OB) (n = 34; BMI ≥25). The primary outcome was body fat content and clinical circulating parameters to assess by correlation analysis CUN-BAE's usefulness as a predictor of metabolic risk. In addition, transcriptomic biomarkers of lipid metabolism were analyzed in peripheral blood mononuclear cells (PBMCs) as secondary outcome indicators of metabolic impairment. Data were analyzed by correlation analysis and comparison of means. RESULTS: CUN-BAE values correlated directly with body fatness obtained by DXA (r = 0.89, P < 0.01), with classical molecular biomarkers of metabolic risk, and with PBMC gene expression of carnitine palmitoyltransferase 1A (CPT1A), sterol regulatory element binding transcription factor 1c (SREBP-1c), and fatty acid synthase (FASN), early markers of metabolic impairment (P < 0.05). Moreover, CUN-BAE allowed identification of NW individuals with excessive body fatness, who were not yet presenting obesity-related molecular alterations. In these subjects, visceral fat correlated directly with circulating glucose, triglycerides, and total and LDL cholesterol, and with triglyceride-glucose and fatty liver indexes (P < 0.05). This is indicative of a metabolically obese NW phenotype. CONCLUSIONS: Data obtained in our cohort of young normoglycemic volunteers support the use of the CUN-BAE index as a tool to estimate accurately body fat mass, but also as a first easy/effective screening tool to identify lean people with increased fat mass and increased metabolic risk.This trial was registered at clinicaltrials.gov as NCT04402697.

U-Shaped Association between Dietary Acid Load and Risk of Osteoporotic Fractures in 2 Populations at High Cardiovascular Risk.

BACKGROUND: Bone contributes to maintaining the acid-base balance as a buffering system for blood pH. Diet composition also affects acid-base balance. Several studies have linked an imbalance in the acid-base system to changes in the density and structure of bone mass, although some prospective studies and meta-analyses suggest that acid load has no deleterious effect on bone. OBJECTIVE: The aim of this study was to examine the associations between potential renal acid load (PRAL) and net endogenous acid production (NEAP) and the risk of osteoporotic fractures and bone mineral density (BMD) in 2 middle-aged and elderly Mediterranean populations. METHODS: We conducted a longitudinal analysis including 870 participants from the PREvención con DIeta MEDiterranea (PREDIMED) Study and a cross-sectional analysis including 1134 participants from the PREDIMED-Plus study. Participants were adults, aged 55-80 y, either at high cardiovascular risk (PREDIMED) or overweight/obese with metabolic syndrome (PREDIMED-Plus), as defined by the International Diabetes Federation, the American Heart Association, and the National Heart Association. PRAL and NEAP were calculated from validated food-frequency questionnaires. BMD was measured using DXA scans. Fracture information was obtained from medical records. The association between mean PRAL and NEAP and fracture risk was assessed using multivariable-adjusted Cox models. BMD differences between tertiles of baseline PRAL and NEAP were evaluated by means of ANCOVA. RESULTS: A total 114 new fracture events were documented in the PREDIMED study after a mean of 5.2 y of intervention and 8.9 y of total follow-up. Participants in the first and third PRAL and NEAP tertiles had a higher risk of osteoporotic fracture compared with the second tertile, showing a characteristically U-shaped association [HR (95% CI): 1.73 (1.03, 2.91) in tertile 1 and 1.91 (1.14, 3.19) in tertile 3 for PRAL, and 1.83 (1.08, 3.09) in tertile 1 and 1.87 (1.10, 3.17) in tertile 3 for NEAP]. Compared with the participants in tertile 1, the participants in the top PRAL and NEAP tertiles had lower BMD [PRAL: mean total femur BMD: 1.029 ± 0.007 and 1.007 ± 0.007 g/cm2; P = 0.006 (tertiles 1 and 3); NEAP: mean total femur BMD: 1.032 ± 0.007 and 1.009 ± 0.007 g/cm2; P = 0.017 (tertiles 1 and 3)]. CONCLUSIONS: The results of our study suggest that both high and low dietary acid are associated with a higher risk of osteoporotic fractures, although only high dietary acid was found to have a negative relation to BMD in senior adults with existing chronic health conditions. This trial was registered at http://www.isrctn.com/ as ISRCTN3573963 (PREDIMED) and ISRCTN89898870 (PREDIMED-Plus).

Neighbourhood walkability and physical activity: moderating role of a physical activity intervention in overweight and obese older adults with metabolic syndrome.

BACKGROUND: While urban built environments might promote active ageing, an infrequently studied question is how the neighbourhood walkability modulates physical activity changes during a physical activity intervention programme in older adults. We assessed the influence of objectively assessed neighbourhood walkability on the change in physical activity during the intervention programme used in the ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial. METHOD: The present study involved 228 PREDIMED-Plus senior participants aged between 55 and 75, recruited in Palma de Mallorca (Spain). Overweight/obese older adults with metabolic syndrome were randomised to an intensive weight-loss lifestyle intervention or a control group. A walkability index (residential density, land use mix, intersections density) was calculated using geographic information systems (1 km sausage-network buffer). Physical activity was assessed using accelerometer and a validated questionnaire, at baseline and two follow-up visits (6-months and 1-year later). Generalised additive mixed models were fitted to estimate the association between the neighbourhood walkability index and changes in physical activity during follow-up. RESULTS: Higher neighbourhood walkability (1 z-score increment) was associated with moderate-to-vigorous accelerometer assessed physical activity duration, (ß = 3.44; 95% CI = 0.52; 6.36 min/day). When analyses were stratified by intervention arm, the association was only observed in the intervention group (ß = 6.357; 95% CI = 2.07;10.64 min/day) (P for interaction = 0.055). CONCLUSIONS: The results indicate that the walkability of the neighbourhood could support a physical activity intervention, helping to maintain or increase older adults' physical activity.

Psychological and metabolic risk factors in older adults with a previous history of eating disorder: A cross-sectional study from the Predimed-Plus study.

GOALS: To explore affective and cognitive status, later in life, in individuals with and without previous history of eating disorder (ED), and also its association with higher risk for metabolic syndrome (MetS) symptomatology. METHODS: A cross-sectional analysis of 6756 adults, aged 55-75 years with overweight/obesity and MetS participating in the Predimed-Plus study was conducted. Participants completed self-reported questionnaires to examine lifetime history of ED, according to DSM-5 criteria, and other psychopathological and neurocognitive factors. Anthropometric and metabolic measurements were also collected. RESULTS: Of the whole sample, 24 individuals (0.35%) reported a previous history of ED. In this subsample, there were more women and singles compared to their counterparts, but they also presented higher levels of depressive symptoms and higher cognitive impairment, but also higher body mass index (BMI) and severe obesity, than those without lifetime ED. CONCLUSIONS: This is one of the first studies to analyse the cognitive and metabolic impact of a previous history of ED. The results showed that previous ED was associated with greater affective and cognitive impairment, but also with higher BMI, later in life. No other MetS risk factors were found, after controlling for relevant variables.

Adherence to a priori dietary indexes and baseline prevalence of cardiovascular risk factors in the PREDIMED-Plus randomised trial.

PURPOSE: Cardiovascular disease remains the global leading cause of death. We evaluated at baseline the association between the adherence to eight a priori high-quality dietary scores and the prevalence of individual and clustered cardiovascular risk factors (CVRF) in the PREDIMED-Plus cohort. METHODS: All PREDIMED-Plus participants (6874 men and women aged 55-75 years, with overweight/obesity and metabolic syndrome) were assessed. The prevalence of 4 CVRF (hypertension, obesity, diabetes, and dyslipidaemia), using standard diagnoses criteria, were considered as outcomes. The adherence to eight a priori-defined dietary indexes was calculated. Multivariable models were fitted to estimate differences in mean values of factors and prevalence ratios for individual and clustered CVRF. RESULTS: Highest conformity to any dietary pattern did not show inverse associations with hypertension. The modified Mediterranean Diet Score (PR = 0.95; 95% CI 0.90-0.99), Mediterranean Diet Adherence Score (MEDAS) (PR = 0.94; 95% CI 0.89-0.98), the pro-vegetarian dietary pattern (PR = 0.95; 95% CI 0.90-0.99) and the Alternate Healthy Eating Index 2010 (PR = 0.92; 95% CI 0.87-0.96) were inversely associated with prevalence of obesity. We identified significant inverse trend among participants who better adhered to the MEDAS and the Prime Diet Quality Score (PDQS) in the mean number of CVRF across categories of adherence. Better adherence to several high-quality dietary indexes was associated with better blood lipid profiles and anthropometric measures. CONCLUSIONS: Highest adherence to dietary quality indexes, especially Mediterranean-style and PDQS scores, showed marginal associations with lower prevalence of individual and clustered CVRF among elderly adults with metabolic syndrome at high risk of cardiovascular disease.

Urinary Resveratrol Metabolites Output: Differential Associations with Cardiometabolic Markers and Liver Enzymes in House-Dwelling Subjects Featuring Metabolic Syndrome.

Metabolic syndrome (MetS) components are strongly associated with increased risk of non-alcoholic fatty liver disease (NAFLD) development. Several studies have supported that resveratrol is associated with anti-inflammatory and antioxidant effects on health status. The main objective of this study was to assess the putative associations between some urinary resveratrol phase II metabolites, cardiometabolic, and liver markers in individuals diagnosed with MetS. In this cross-sectional study, 266 participants from PREDIMED Plus study (PREvención con DIeta MEDiterránea) were divided into tertiles of total urinary resveratrol phase II metabolites (sum of five resveratrol conjugation metabolites). Urinary resveratrol metabolites were analyzed by ultra- performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS), followed by micro-solid phase extraction (µ-SPE) method. Liver function markers were assessed using serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Moreover, lipid profile was measured by triglycerides, very-low-density lipoprotein cholesterol (VLDL-c), and total cholesterol/high-density lipoprotein ratio (total cholesterol/HDL). Linear regression adjusted models showed that participants with higher total urine resveratrol concentrations exhibited improved lipid and liver markers compared to the lowest tertile. For lipid determinations: log triglycerides (ßT3= -0.15, 95% CI; -0.28, -0.02, p-trend = 0.030), VLDL-c, (ßT3= -4.21, 95% CI; -7.97, -0.46, p-trend = 0.039), total cholesterol/HDL ratio Moreover, (ßT3= -0.35, 95% CI; -0.66, -0.03, p-trend = 0.241). For liver enzymes: log AST (ßT3= -0.12, 95% CI; -0.22, -0.02, p-trend = 0.011, and log GGT (ßT3= -0.24, 95% CI; -0.42, -0.06, p-trend = 0.002). However, there is no difference found on glucose variables between groups. To investigate the risk of elevated serum liver markers, flexible regression models indicated that total urine resveratrol metabolites were associated with a lower risk of higher ALT (169.2 to 1314.3 nmol/g creatinine), AST (599.9 to 893.8 nmol/g creatinine), and GGT levels (169.2 to 893.8 nmol/g creatinine). These results suggested that higher urinary concentrations of some resveratrol metabolites might be associated with better lipid profile and hepatic serum enzymes. Moreover, urinary resveratrol excreted showed a reduced odds ratio for higher liver enzymes, which are linked to NAFLD.

Longitudinal association of changes in diet with changes in body weight and waist circumference in subjects at high cardiovascular risk: the PREDIMED trial.

BACKGROUND: Consumption of certain foods is associated with long-term weight gains and abdominal fat accumulation in healthy, middle-aged and young, non-obese participants. Whether the same foods might be associated with changes in adiposity in elderly population at high cardiovascular risk is less known. OBJECTIVE: Using yearly repeated measurements of both food habits and adiposity parameters, we aimed to investigate how changes in the consumption of specific foods were associated with concurrent changes in weight or waist circumference (WC) in the PREDIMED trial. DESIGN: We followed-up 7009 participants aged 55-70 years at high cardiovascular risk for a median time of 4.8 years. A validated 137-item semi-quantitative Food Frequency Questionnaire was used for dietary assessment with yearly repeated measurements. We longitudinally assessed associations between yearly changes in food consumption (serving/d) and concurrent changes in weight (kg) or WC (cm). RESULTS: Yearly increments in weight were observed with increased consumption (kg per each additional increase in 1 serving/d) for refined grains (0.32 kg/serving/d), red meat (0.24), potatoes (0.23), alcoholic beverages (0.18), processed meat (0.15), white bread (0.07) and sweets (0.04); whereas inverse associations were detected for increased consumption of low-fat yogurt (- 0.18), and low-fat milk (- 0.06). Annual WC gain (cm per each additional increase in 1 serving/d) occurred with increased consumption of snacks, fast-foods and pre-prepared dishes (0.28), processed meat (0.18), alcoholic beverages (0.13), and sweets (0.08); whereas increased consumption of vegetables (- 0.23), and nuts (- 0.17), were associated with reductions in WC. CONCLUSIONS: In this assessment conducted in high-risk subjects using yearly repeated measurements of food habits and adiposity, some ultra-processed foods, refined carbohydrates (including white bread), potatoes, red meats and alcohol were associated with higher weight and WC gain, whereas increases in consumption of low-fat dairy products and plant foods were associated with less gain in weight and WC. TRIAL REGISTRATION: This study was registered at controlled-trials.com with International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study.

BACKGROUND: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. METHODS: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. RESULTS: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). CONCLUSIONS: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

DiabeText, a mobile health intervention to support medication taking and healthy lifestyle in adults with type 2 diabetes: Study protocol for a randomized controlled trial.

AIM: To evaluate the effectiveness of DiabeText, a low-intensity, multifaceted, mobile health (mHealth) intervention to support medication taking and lifestyle change targeted to people with type 2 diabetes (T2D). DESIGN: Phase III, 12-months, two-arm (1:1 allocation ratio), randomized parallel-group trial. METHODS: We will recruit 740 adults with glycated hemoglobin (A1c) >8% (>64 mmol/mol) and with at least one prescription of a non-insulin antidiabetic drug. They will be allocated to a control (usual care) group or an intervention (DiabeText messaging intervention) group. The primary outcome measure will be A1c at 12 months follow-up. Secondary outcomes will include medication possession ratio and behavioral and psychological outcomes. DISCUSSION: Recent trials suggest that digital health interventions can effectively support diabetes self-management improving T2D control and reducing important T2D complications. In Spain this type of interventions is understudied. IMPACT: This trial will strengthen the evidence base of the impact of mHealth interventions to support diabetes self-management. If effective, DiabeText may offer a low-cost and highly scalable strategy to improve health at the population level in a sustainable way. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05006872; Official Title: Supporting People with Type 2 Diabetes in Effective Use of their Medicine Through a System Comprising Mobile Health Technology Integrated with Clinical Care.

Whole-Genome Transcriptomics of PBMC to Identify Biomarkers of Early Metabolic Risk in Apparently Healthy People with Overweight-Obesity and in Normal-Weight Subjects.

SCOPE: Peripheral blood mononuclear cells (PBMC) provide a useful and minimally invasive source of biomarkers. Here to identify PBMC transcriptomic biomarkers predictive of metabolic impairment related to increased adiposity is aimed. METHODS AND RESULTS: The study analyzed the global PBMC transcriptome in metabolically healthy (normoglycemic) volunteers with overweight-obesity (OW-OB, n = 12), and in subjects with metabolically obese normal-weight (MONW, n = 5) phenotype, in comparison to normal-weight (NW, n = 12) controls. The study identifies 1072 differentially expressed genes (DEGs) in OW-OB versus NW and 992 in MONW versus NW. Hierarchical clustering of the top 100 DEGs clearly distinguishes OW-OB and MONW from NW. Remarkably, the OW-OB and MONW phenotypes share 257 DEGs regulated in the same direction. The top up-regulated gene CXCL8, coding for interleukin 8, with a role in obesity-related pathologies, is of special interest as a potential marker for predicting increased metabolic risk. CXCL8 expression is increased mainly in the MONW group and correlated directly with C-reactive protein levels. CONCLUSIONS: PBMC gene expression analysis of CXCL8 or a pool of DEGs may be used to identify early metabolic risk in an apparently healthy population regardless of their BMI, i.e., subjects with OW-OB or MONW phenotype and to apply adequate and personalized nutritional preventive strategies.

Non-adherence to non-insulin glucose-lowering drugs: Prevalence, predictors and impact on glycemic control and insulin initiation. A longitudinal cohort study in a large primary care database in Spain.

BACKGROUND: A better understanding of patient non-adherence to type 2 diabetes medication is needed to design effective interventions to address this issue. OBJECTIVES: (1) To estimate the prevalence of non-adherence to diabetes medication; (2) to examine its impact on glycemic control and insulin initiation; (3) to develop and validate a prediction model of non-adherence. METHODS: We conducted a longitudinal cohort study based on data from electronic health records. We included adult patients registered within the Health Service of the Balearic Islands (Spain) starting a new prescription of a non-insulin glucose-lowering drug between January 2016 and December 2018. We calculated non-adherence at 12 months follow-up, defined as medication possession ratio (MPR) ≤ 80%. We fitted multivariable regression models to examine the association between non-adherence and glycemic control and insulin initiation and identified predictors of non-adherence. RESULTS: Of 18,119 patients identified, after 12 months follow-up, 5,740 (31.68%) were non-adherent. Compared with non-adherent, adherent patients presented lower HbA1c levels (mean difference = -0.32%; 95%CI = -0.38%; -0.27%) and were less likely to initiate insulin (aOR = 0.77; 95%CI = 0.63; 0.94). A predictive model explained 22.3% of the variation and presented a satisfactory performance (AUC = 0.721; Brier score = 0.177). The most important predictors of non-adherence were: non-Spanish nationality, currently working, low adherence to previous drugs, taking biguanides, smoker and absence of hypertension. CONCLUSION: Around one-third of the patients do not adhere to their non-insulin glucose-lowering drugs. More research is needed to optimise the performance of the predicting model before considering its implementation in routine clinical practice.

Estimated Phytate Intake Is Associated with Bone Mineral Density in Mediterranean Postmenopausal Women.

The main objective of this work was to explore the association of dietary phytate intake with bone mineral density (BMD) in a Mediterranean population of postmenopausal women. For this purpose, a cross-sectional analysis of 561 women aged 55-75 years with overweight/obesity and metabolic syndrome from a Mediterranean area and with data on dual-energy X-ray absorptiometry (DXA) scans in femur and lumbar spine was performed. Estimated phytate intake was calculated using a validated food frequency questionnaire. Our results indicated that phytate intake was associated with BMD [ß(95%CI) per each 25 mg/100 kcal] in femoral neck [0.023(0.060-0.040) g/cm2], femoral Ward's triangle [0.033(0.013-0.054) g/cm2], total femur [0.018(0.001-0.035) g/cm2], and all the analyzed lumbar spine sites [L1-L4: 0.033(0.007-0.059) g/cm2] after adjusting for potential confounders. The sensitivity analysis showed that phytate intake was directly associated with lumbar spine BMD in women younger than 66 years, with a body mass index higher than 32.6 kg/cm2 and without type 2 diabetes (all p-for interactions < 0.05). The overall results indicated that phytate, a substance present in food as cereals, legumes and nuts, was positively associated with BMD in Mediterranean postmenopausal women. Phytate may have a protective effect on bone resorption by adsorbing on the surfaces of HAP. Nevertheless, large, long-term, and randomized prospective clinical studies must be performed to assess the possible benefits of phytate consumption on BMD in postmenopausal women.

Loss of Visceral Fat is Associated with a Reduction in Inflammatory Status in Patients with Metabolic Syndrome.

SCOPE: Excessive visceral adipose tissue (VAT) is associated with higher secretion of pro-inflammatory molecules, contributing to systemic inflammation and obesity-related metabolic disturbances. METHODS AND RESULTS: This prospective analysis includes 117 overweight/obese adults (55-75 years) from the PREDIMED-Plus study. Fourteen inflammatory markers and adipokines are measured using a Bio-Plex assay with multiplex technology: insulin, glucagon, IL-6, visfatin, ghrelin, GLP-1, TNF-α, MCP-1, PAI-1, resistin, C-peptide, leptin, adipsin, and adiponectin. Participants are categorized into tertiles according to changes in VAT after 1-year of follow-up, determined by dual-energy X-Ray absorptiometry. Participants allocate in tertile 3, which represent an increase of VAT content after 1-year of follow-up compared to tertile 1, show significant differences in insulin (T3 vs T1, fully adjusted model: p = 0.037, p for trend 0.042), PAI-1 (fully adjusted model: p = 0.05, p for trend 0.06), c-peptide (fully adjusted model: p = 0.037, p for trend 0.042), and TNF-α (fully adjusted model p = 0.037, p for trend 0.042). CONCLUSION: The results evidence that a reduction in VAT is associated with clinical improvements in several inflammatory and adiposity markers, mainly in insulin, c-peptide, and PAI-1 levels, and these improvements may contribute to a reduction in cardiometabolic disturbances observe in obesity.

Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat.

BACKGROUND & AIMS: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies. The aim of the study was to longitudinally assess the association of changes in coffee and caffeine intake with changes in fat tissue, in particular, visceral adipose tissue (VAT) using dual x-ray absorptiometry (DXA). METHODS: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome (MetS). Repeated measurements of coffee consumption from validated food frequency questionnaires (FFQ) and DXA measurements of adipose tissue were collected at baseline, 6 months, 12 months and 3 years of follow-up. DXA-derived measurements of total and regional adipose tissue expressed as % of total body weight were transformed into sex-specific z-scores. Linear multilevel mixed-effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue during a 3-year follow-up. RESULTS: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤3 cups/month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95% CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95% CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95% CI: -0.13 to -0.01). Neither changes from no or infrequent consumption to high levels of caffeinated coffee consumption (>1 cup/day) nor any changes in decaffeinated coffee consumption showed significant associations with changes in DXA measures. CONCLUSIONS: Moderate changes in the consumption of caffeinated coffee, but not changes to high consumption, were associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with MetS. Decaffeinated coffee was not linked to adiposity indicators. Moderate consumption of caffeinated coffee may be part of a weight management strategy. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition: An Interim Subgroup Analysis of the PREDIMED-Plus Randomized Clinical Trial.

Importance: Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. Objective: To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. Design, Setting, and Participants: The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. Intervention: Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. Main Outcomes and Measures: The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). Results: A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. Conclusions and Relevance: The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. Trial Registration: isrctn.org Identifier: ISRCTN89898870.