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.

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.

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.

Association of monetary diet cost of foods and diet quality in Spanish older adults.

Background: A major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods. Objectives: This study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease. Methods: Cross-sectional analysis was carried out in Spanish older adults (n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015-2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed. Results: The healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet. Conclusion: Higher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases. Clinical trial registry number: The trial was registered in 2014 at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870) with the number 89898870.

Increased ultra-processed food consumption is associated with worsening of cardiometabolic risk factors in adults with metabolic syndrome: Longitudinal analysis from a randomized trial.

BACKGROUND AND AIMS: The association between changes in ultra-processed food (UPF) consumption and cardiometabolic risk (CMR) factors remains understudied. We evaluated the association between changes in UPF consumption over 12 months of follow-up and changes in CMR factors in adults diagnosed with metabolic syndrome. METHODS: We analysed data from 5373 adults (aged 55-75 years) participating in the PREDIMED-Plus trial. Diet was evaluated at baseline, 6- and 12-month visits using a validated food frequency questionnaire, and UPF consumption (in grams/day and percentage of total daily dietary intake in grams) was categorized based on NOVA classification. We used mixed-effects linear models with repeated measurements at baseline, 6 and 12 months of follow-up to assess the associations between changes in UPF consumption and changes in CMR factors adjusting for sociodemographic and lifestyles variables. RESULTS: In multivariable-adjusted models, when comparing the highest versus the lowest quartile of UPF consumption, positive associations were found for several CMR factors: weight (kg, ß = 1.09; 95% confidence interval 0.91 to 1.26); BMI (kg/m2, ß = 0.39; 0.33 to 0.46); waist circumference (cm, ß = 1.03; 0.81 to 1.26); diastolic blood pressure (mm Hg, ß = 0.67; 0.29 to 1.06); fasting blood glucose (mg/dl, ß = 1.66; 0.61 to 2.70); HbA1c (%, ß = 0.04; 0.01 to 0.07); triglycerides (mg/dl, ß = 6.79; 3.66 to 9.91) and triglycerides and glucose index (ß = 0.06; 0.04 to 0.08). CONCLUSIONS: Higher UPF consumption was associated with adverse evolution in objectively measured CMR factors after 12 months of follow-up in adults with metabolic syndrome. Further research is needed to explore whether these changes persist for longer periods.

Ultra-processed foods consumption as a promoting factor of greenhouse gas emissions, water, energy, and land use: A longitudinal assessment.

BACKGROUND: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability. OBJECTIVES: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use. DESIGN: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome. METHODS: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models. RESULTS: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO2eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced. CONCLUSIONS: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection. TRIAL REGISTRATION: ISRCTN, ISRCTN89898870. Registered 05 September 2013, http://www.isrctn.com/ISRCTN89898870.

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.

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.

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.

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.

Health associations of liver enzymes and inflammatory scores with urinary citrus flavonoid metabolites.

Background: Dietary flavonoid intake is associated with a reduced risk of some cardiometabolic disorders, attributed in part to their claimed anti-inflammatory activity. Our aim was to investigate the potential association between specific urine flavonoid metabolites, liver enzymes, and inflammatory status in individuals with metabolic syndrome (MetS). Methods: In this cross-sectional study, clinical and dietary data from 267 participants, aged 55 to 75 years, participating in the PREDIMED Plus study (PREvención con DIeta MEDiterránea) were analyzed. At the baseline, spot urine samples were collected and seven urinary flavonoid metabolites were quantified using ultra-performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS). Liver enzymes, inflammatory scores, and urinary flavonoid concentrations were inverse normally transformed. Results: Adjusted linear regression models showed an inverse association between urinary citrus flavanone concentrations and gamma-glutamyl transferase (GGT) (all p-values <0.05). Naringenin 7'-GlcUA was significantly associated with a lower aggregate index of systemic inflammation (AISI) (Bper 1SD = -0.14; 95% CI: -0.27 to -0.02; p-value = 0.025) and systemic inflammation index (SII) (Bper 1SD = -0.14; 95% CI: -0.27 to -0.02; p-value = 0.028). To investigate the relationship between flavanone subclasses and GGT levels, we fitted a score of citrus-flavanones, and subjects were stratified into quartiles. The highest values of the citrus-flavanone score (per 1-SD increase) were associated with lower GGT levels (Bper 1SD = -0.41; 95% CI: -0.74 to -0.07), exhibiting a linear trend across quartiles (p-trend = 0.015). Conclusion: This cross-sectional study showed that higher urinary excretion of citrus-flavanone metabolites was associated with lower GGT levels in subjects diagnosed with MetS and obesity.

Efficacy of Different Modalities and Frequencies of Physical Exercise on Glucose Control in People with Prediabetes (GLYCEX Randomised Trial).

To assess the efficacy of different modalities and frequencies of physical exercise on glycaemic control in adults with prediabetes. A two-phase, parallel, randomised, controlled clinical trial will be carried out, in 210 participants. In phase 1, 120 participants will be randomized into four arms: (1) aerobic exercise, (2) aerobic exercise combined with resistance, (3) high-intensity intervallic exercise and (4) control group. In phase 2, 90 new participants will be randomized into three arms, using the exercise modality that showed the best glycaemic control in phase 1 in the following manner: (1) frequency of 5 days/week, (2) frequency of 3 days/week and (3) frequency of 2 days/week. The control group (n = 30) will be included in phase 1 to evaluate the effect of any type of intervention versus no intervention. Data collection will be performed at baseline and after 15 weeks of follow up. Sociodemographic data, medication, comorbidity, blood biochemical parameters, blood pressure, anthropometric measurements, body composition, physical activity, sedentary lifestyle, diet, smoking, alcohol consumption, quality of life and sleep questionnaires will be collected. Physical activity, sedentary behaviour and sleep will be further determined with an accelerometer, and continuous glycaemia will be determined with a glycaemic monitor, both during seven days, at two time points. The main dependent variable will be the reduction in the mean amplitude of glycaemic excursions. The impact of these interventions on health will also be evaluated through gene expression analysis in peripheral blood cells. The results of this study will contribute to a better understanding of the mechanisms behind the glucose response to physical exercise in a population with prediabetes as well as improve physical exercise prescriptions for diabetes prevention. Increasing glycaemic control in people with prediabetes through physical exercise offers an opportunity to prevent diabetes and reduce associated comorbidities and health costs.

Development and Evaluation of a Digital Health Intervention to Prevent Type 2 Diabetes in Primary Care: The PREDIABETEXT Study Protocol for a Randomised Clinical Trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a highly prevalent disease associated with an increased risk of comorbidities, premature death, and health costs. Prediabetes is a stage of glucose alteration previous to T2DM, that can be reversed. The aim of the study is to develop and evaluate a low-intensity, multifaceted, digital intervention to prevent T2DM. The intervention comprises: (1) the use of mobile health technology to send tailored text messages promoting lifestyle changes to people at risk of T2DM and (2) the provision of online education to primary healthcare physicians and nurses about management of prediabetes. METHODS: In stages 1-4 we will design, develop and pilot-test the intervention. In Stage 5 we will conduct a phase II, six-month, three-arm, cluster randomized, clinical trial with 42 primary care professionals and 420 patients at risk of T2DM. Patients will be allocated to a control group (usual care), intervention A (patient messaging intervention), or intervention B (patient messaging intervention plus online education to their primary healthcare professionals). The primary outcome will be glycated haemoglobin. All the procedures obtained ethical approval in June 2021 (CEI-IB Ref No: IB4495/21PI). DISCUSSION: Digital health interventions can effectively prevent T2DM and reduce important T2DM risk factors such as overweight or hypertension. In Spain, this type of intervention is understudied. Moreover, there is controversy regarding the type of digital health interventions that are more effective. Findings from this study may contribute to address T2DM prevention, through a low-cost and easily implementable intervention.

Does Consumption of Ultra-Processed Foods Matter for Liver Health? Prospective Analysis among Older Adults with Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver alterations that can result in severe disease and even death. Consumption of ultra-processed foods (UPF) has been associated with obesity and related comorbidities. However, the link between UPF and NAFLD has not been sufficiently assessed. We aimed to investigate the prospective association between UPF consumption and liver health biomarkers. Methods: We followed for 1 year 5867 older participants with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus trial. A validated 143-item semi-quantitative food frequency questionnaire was used to evaluate consumption of UPF at baseline, 6, and 12 months. The degree of processing for foods and beverages (g/day) was established according to the NOVA classification system. The non-invasive fatty liver index (FLI) and hepatic steatosis index (HSI) were used to evaluate liver health at three points in time. The associations between changes in UPF consumption (percentage of total daily dietary intake (g)) and liver biomarkers were assessed using mixed-effects linear models with repeated measurements. Results: In this cohort, UPF consumption at baseline was 8.19% (SD 6.95%) of total daily dietary intake in grams. In multivariable models, each 10% daily increment in UPF consumption in 1 year was associated with significantly greater FLI (ß 1.60 points, 95% CI 1.24;1.96 points) and HSI (0.43, 0.29; 0.57) scores (all p-values < 0.001). These associations persisted statistically significant after adjusting for potential dietary confounders and NAFLD risk factors. Conclusions: A higher UPF consumption was associated with higher levels of NAFLD-related biomarkers in older adults with overweight/obesity and MetS.

Longitudinal association of dietary carbohydrate quality with visceral fat deposition and other adiposity indicators.

BACKGROUND & AIMS: The quality of dietary carbohydrates rather than total carbohydrate intake may determine the accumulation of visceral fat; however, to date, few studies have examined the impact of diet on adiposity using specific imaging techniques. Thus, the aim of this prospective study was to investigate the association between concurrent changes in carbohydrate quality index (CQI) and objectively-quantified adiposity distribution over a year. METHODS: We analyzed a cohort of 1476 participants aged 55-75 years with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus randomized controlled trial. Dietary intake information was obtained at baseline, 6- and 12-months from a validated 143-item semi-quantitative food-frequency questionnaire, and CQI (range: 4 to 20) was calculated based on four dietary criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio. Overall and regional adiposity (total body fat, visceral fat and android-to-gynoid fat ratio) was quantified using dual-energy X-ray absorptiometry at all three time points. Multiple adjusted linear mixed-effects models were used to assess associations between concurrent changes in repeatedly measured CQI and adiposity over time. RESULTS: After controlling for potential confounding factors, a 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (ß -0.067 z-score, 95% CI -0.088; -0.046, p < 0.001), android-to-gynoid fat ratio (-0.038, -0.059; -0.017, p < 0.001), and total fat (-0.064, -0.080; -0.047, p < 0.001). Fibre intake and the ratio of wholegrain/total grain showed the strongest inverse associations with all adiposity indicators. CONCLUSIONS: In this prospective cohort of older adults with overweight/obesity and MetS, we found that improvements in dietary carbohydrate quality over a year were associated with concurrent favorable changes in visceral and overall fat deposition. These associations were mostly driven by dietary fibre and the wholegrain/total grain ratio. 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.

Role of NAFLD on the Health Related QoL Response to Lifestyle in Patients With Metabolic Syndrome: The PREDIMED Plus Cohort.

Objective: To evaluate the effect of Non-alcoholic fatty liver disease (NAFLD) status in the impact of lifestyle over Health-related quality of life (HRQoL) in patients with metabolic syndrome (MetS). Methods: Baseline and 1 year follow up data from the PREDIMED-plus cohort (men and women, 55-75 years old with overweight/obesity and MetS) were studied. Adherence to an energy-restricted Mediterranean Diet (er-MeDiet) and Physical Activity (PA) were assessed with a validated screeners. Hepatic steatosis index (HSI) was implemented to evaluate NAFLD while the SF-36 questionnaire provided HRQoL evaluation. Statistical analyses were performed to evaluate the influence of baseline NAFLD on HRQoL as affected by lifestyle during 1 year of follow up. Results: Data from 5205 patients with mean age of 65 years and a 48% of female participants. Adjusted linear multivariate mixed regression models showed that patients with lower probability of NAFLD (HSI < 36 points) were more responsive to er-MeDiet (ß 0.64 vs ß 0.05 per er-MeDiet adherence point, p< 0.01) and PA (ß 0.05 vs ß 0.01 per MET-h/week, p = 0.001) than those with high probability for NAFLD in terms Physical SF-36 summary in the 1 year follow up. 10 points of er-MeDiet adherence and 50 MET-h/week were thresholds for a beneficial effect of lifestyle on HRQoL physical domain in patients with lower probability of NAFLD. Conclusion: The evaluation of NAFLD by the HSI index in patients with MetS might identify subjects with different prospective sensitivity to lifestyle changes in terms of physical HRQoL (http://www.isrctn.com/ISRCTN89898870).

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.

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.

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.