Effect of a Very-Low-Calorie Ketogenic Diet on Circulating Myokine Levels Compared with the Effect of Bariatric Surgery or a Low-Calorie Diet in Patients with Obesity

The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet

MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1

The prevalence of metabolic syndrome (MetS) and obesity is an alarming health issue worldwide. Obesity is characterized by an excessive accumulation of white adipose tissue (WAT), and it is associated with diminished brown adipose tissue (BAT) activity. Twist1 acts as a negative feedback regulator of BAT metabolism. Therefore, targeting Twist1 could become a strategy for obesity and metabolic disease. Here, we have identified miR-337-3p as an upstream regulator of Twist1. Increased miR-337-3p expression paralleled decreased expression of TWIST1 in BAT compared to WAT. Overexpression of miR-337-3p in brown pre-adipocytes provoked a reduction in Twist1 expression that was accompanied by increased expression of brown/mitochondrial markers. Luciferase assays confirmed an interaction between the miR-337 seed sequence and Twist1 3 0UTR. The inverse relationship between the expression of TWIST1 and miR-337 was finally validated in adipose tissue samples from non-MetS and MetS subjects that demonstrated a dysregulation of the miR-337-Twist1 molecular axis in MetS. The present study demonstrates that adipocyte miR-337-3p suppresses Twist1 repression and enhances the browning of adipocytes

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk:Rationale and design of the ODYSSEY DM-INSULIN trial

Aims: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. Methods: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening. ≥. 70. mg/dL (1.81. mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24. weeks of alirocumab 75. mg every 2. weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C. ≥. 70. mg/dL at week 8 underwent a blinded dose increase to 150. mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. Results: This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. Conclusion: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMEDPlus 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

Total and Subtypes of Dietary Fat Intake and Its Association with Components of the Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Risk

Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on cardiovascular disease (CVD) remains unclear in individuals at high CVD risk. Objective: To assess the association between fat intake and MetS components in an adult Mediterranean population at high CVD risk. Design: Baseline assessment of nutritional adequacy in participants (n = 6560, men and women, 55-75 years old, with overweight/obesity and MetS) in the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial. Methods: Assessment of fat intake (total fat, monounsatured fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, α-linolenic acid, and ω-3 FA) using a validated food frequency questionnaire, and diet quality using 17-item Mediterranean dietary questionnaire and fat quality index (FQI). Results: Participants in the highest quintile of total dietary fat intake showed lower intake of energy, carbohydrates, protein and fiber, but higher intake of PUFA, MUFA, SFA, TFA, LA, ALA and ω-3 FA. Differences in MetS components were found according to fat intake. Odds (5th vs. 1st quintile): hyperglycemia: 1.3-1.6 times higher for total fat, MUFA, SFA and ω-3 FA intake; low high-density lipoprotein cholesterol (HDL-c): 1.2 higher for LA; hypertriglyceridemia: 0.7 lower for SFA and ω-3 FA intake. Conclusions: Dietary fats played different role on MetS components of high CVD risk patients. Dietary fat intake was associated with higher risk of hyperglycemia

Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk

The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. Methods: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. Results: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). Conclusions: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed

Effectiveness of the physical activity intervention program in the PREDIMED-Plus study: a randomized controlled trial

Background: The development and implementation of effective physical activity (PA) intervention programs is challenging, particularly in older adults. After the first year of the intervention program used in the ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial, we assessed the initial effectiveness of the PA component. Methods: PREDIMED-Plus is an ongoing randomized clinical trial including 6874 participants randomized to an intensive weight-loss lifestyle intervention based on an energy-restricted Mediterranean diet (MedDiet), physical activity promotion and behavioral support and to a control group using MedDiet recommendations but without calorie restriction or PA advice. Body mass index (BMI) and waist circumference (WC) are measured by standard clinical protocols. Duration and intensity of PA is self-reported using the validated REGICOR Short Physical Activity Questionnaire. The primary endpoint of the PREDIMED-Plus trial is a combined cardiovascular outcome: myocardial infarction (acute coronary syndromes with positive troponin test), stroke, or cardiovascular mortality. The present study involved secondary analysis of PA data (n = 6059; mean age 65 ± 4.9 years) with one-year changes in total, light, and moderate-to-vigorous PA within and between intervention groups as the outcome. Generalized estimating equation models were fitted to evaluate time trends of PA, BMI, and WC within groups and differences between intervention and control groups. Results: After 12 months, average daily MVPA increased by 27.2 (95%CI 5.7;48.7) METs-min/day and 123.1 (95%CI 109. 7–136.6) METs-min/day in the control and intervention groups, respectively. Total-PA, light-PA, and MVPA increased significantly (p < 0.01) in both groups. A significant (p < 0.001) time*intervention group interaction was found for Total-PA and MVPA, meaning the PA trajectory over time differed between the intervention and control groups. Age, sex, education level, and BMI did not moderate the effectiveness of the PA intervention. BMI and WC decreased significantly with increasing MVPA, compared with participants who reported no changes in MVPA.Conclusion: After one year of follow-up, the PREDIMED-Plus PA intervention has been effective in increasing daily PA in older adult

Seafood Consumption, Omega-3 Fatty Acids Intake, and Life-Time Prevalence of Depression in the PREDIMED-Plus Trial

Background: The aim of this analysis was to ascertain the type of relationship between fish and seafood consumption, omega-3 polyunsaturated fatty acids (ω-3 PUFA) intake, and depression prevalence. Methods: Cross-sectional analyses of the PREDIMED-Plus trial. Fish and seafood consumption and ω-3 PUFA intake were assessed through a validated food-frequency questionnaire. Self-reported life-time medical diagnosis of depression or use of antidepressants was considered as outcome. Depressive symptoms were collected by the Beck Depression Inventory-II. Logistic regression models were used to estimate the association between seafood products and ω-3 PUFA consumption and depression. Multiple linear regression models were fitted to assess the association between fish and long-chain (LC) ω-3 PUFA intake and depressive symptoms. Results: Out of 6587 participants, there were 1367 cases of depression. Total seafood consumption was not associated with depression. The odds ratios (ORs) (95% confidence intervals (CIs)) for the 2nd, 3rd, and 4th quintiles of consumption of fatty fish were 0.77 (0.63–0.94), 0.71 (0.58–0.87), and 0.78 (0.64–0.96), respectively, and p for trend = 0.759. Moderate intake of total LC ω-3 PUFA (approximately 0.5–1 g/day) was significantly associated with a lower prevalence of depression. Conclusion: In our study, moderate fish and LC ω-3 PUFA intake, but not high intake, was associated with lower odds of depression suggesting a U-shaped relationship

Dietary diversity and nutritional adequacy among an older Spanish population with Metabolic Syndrome in the PREDIMED-Plus study: a cross-sectional analysis

Dietary guidelines emphasize the importance of a varied diet to provide an adequate nutrient intake. However, an older age is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases, such as metabolic syndrome (MetS). To assess the association between dietary diversity (DD) and nutrient intake adequacy and to identify demographic variables associated with DD, we cross-sectionally analyzed baseline data from the PREDIMED-Plus trial: 6587 Spanish adults aged 55–75 years, with overweight/obesity who also had MetS. An energy-adjusted dietary diversity score (DDS) was calculated using a 143-item validated semi-quantitative food frequency questionnaire (FFQ). Nutrient inadequacy was defined as an intake below 2/3 of the dietary reference intake (DRI) forat least four of 17 nutrients proposed by the Institute of Medicine (IOM). Logistic regression models were used to evaluate the association between DDS and the risk of nutritionally inadequate intakes. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake: odds ratio (OR) = 28.56 (95% confidence interval (CI) 20.80–39.21). When we estimated food varietyfor each of the food groups, participants in the lowest quartile had a higher risk of inadequate nutrient intake for the groups of vegetables, OR = 14.03 (95% CI 10.55–18.65), fruits OR = 11.62 (95% CI 6.81–19.81), dairy products OR = 6.54 (95% CI 4.64–9.22) and protein foods OR = 6.60 (95% CI 1.96–22.24). As DDS decreased, the risk of inadequate nutrients intake rose. Given the impact of nutrient intake adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow(er)s. View Full-Tex