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.

Bariatric Surgery Outcomes in Patients with Chronic Kidney Disease.

Obesity increases the risk of developing chronic kidney disease (CKD), which has a major negative impact on global health. Bariatric surgery (BS) has demonstrated a substantial improvement of obesity-related comorbidities and thus, it has emerged as a potential therapeutic tool in order to prevent end-stage renal disease. A limited number of publications to date have examined the beneficial effects and risks of BS in patients with non-advanced stages of CKD. We aimed to investigate the safety of BS in patients with CKD stages 3-4 (directly related or not to obesity) and both the metabolic/renal outcomes post-BS. A total of 57 individuals were included (n = 19 for CKD-group; n = 38 for patients with obesity, but normal eGFR [control-group]). Weight loss and obesity comorbidities resolution after BS were similar in both groups. Renal function (eGFR [CKD-EPI]) improved significantly at the 1-year follow-up: Δ10.2 (5.2-14.9) (p < 0.001) for CKD-group and Δ4.0 (-3.9-9.0) mL/min/1.73 m2 (p = 0.043) for controls. Although this improvement tended to decrease in the 5-year follow-up, eGFR remained above its basal value for the CKD-group. Noteworthy, eGFR also improved in those patients who presented CKD not directly attributed to obesity. For patients with CKD, BS appears to be safe and effective regarding weight loss and obesity comorbidities resolution, irrespective of the main cause of CKD (related or not to obesity).

Expression of Adipose Tissue Extracellular Matrix-Related Genes Predicts Weight Loss after Bariatric Surgery.

BACKGROUND: We evaluated the association between white adipose tissue parameters before bariatric surgery (BS) and post-surgical weight loss, with an especial focus on extracellular matrix (ECM) gene expression. METHODS: Paired samples from subcutaneous (SAT) and visceral adipose tissue (VAT) were obtained from 144 subjects undergoing BS. The association between total body weight loss (%TBWL) at 12 months after BS and the histological characteristics and gene expression of selected genes in SAT and VAT was analyzed. RESULTS: Fat cell area, size-frequency distribution, and fibrosis in SAT or VAT prior to surgery were not associated with %TBWL. On the contrary, the SAT expression of COL5A1 and COL6A3 was associated with %TBWL after BS (both p < 0.001), even after adjusting for age, gender, baseline BMI, and type 2 diabetes status (T2D). Furthermore, in logistic regression analyses, the expression of these genes was significantly associated with insufficient WL (IWL = TBWL < 20%) after BS (respectively, p = 0.030 and p = 0.031). Indeed, in ROC analysis, the prediction of IWL based on sex, age, BMI, T2D, and the type of surgery (AUC = 0.71) was significantly improved with the addition of SAT-COL5A1 gene expression (AUC = 0.88, Z = 2.13, p = 0.032). CONCLUSIONS: Our data suggest that the expression of SAT ECM-related genes may help explain the variability in TBWL following BS.

Bariatric Surgery Outcomes in Patients with Kidney Transplantation.

Obesity and kidney transplantation (KTx) are closely related. Obesity increases the risk of chronic kidney disease and can be a relative contraindication for KTx. Besides, KTx recipients are predisposed to obesity and its comorbidities. Consequently, bariatric surgery (BS) emerges as a powerful therapeutic tool either before or after KTx. Since evidence regarding the best approach is still scarce, we aimed to describe renal and metabolic outcomes in a single centre with more than 15-year experience in both surgeries. METHODS: A retrospective study including patients who had received a KTx either before or after BS. Usual metabolic and renal outcomes, but also new variables (as renal graft dysfunction) were collected for a minimum follow-up of 1-year post-BS. RESULTS: A total of 11 patients were included: n = 6 (BS-post-KTx) and n = 5 (BS-pre-KTx). One patient was assessed in both groups. No differences in the main outcomes were identified, but BS-post-KTx group tended to gain more weight during the follow-up. The incidence of renal graft dysfunction was comparable (4/6 for BS-post-KTx, 3/5 for BS-pre-KTx) between groups. CONCLUSIONS: BS in patients with KTx appears to be safe and effective attending to metabolic and renal outcomes. These results seem irrespective of the time course, except for weight regain, which appears to be a common pattern in the BS-post-KTx group.

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.

Positive Effects of a Mediterranean Diet Supplemented with Almonds on Female Adipose Tissue Biology in Severe Obesity.

It has been suggested that weight-loss-independent Mediterranean diet benefits on cardiometabolic health and diabetes prevention may be mediated, at least in part, through the modulation of white adipose tissue (WAT) biology. This study aimed to evaluate the short-term effects of a dietary intervention based on the Mediterranean diet supplemented with almonds (MDSA) on the main features of obesity-associated WAT dysfunction. A total of 38 women with obesity were randomly assigned to a 3-month intervention with MDSA versus continuation of their usual dietary pattern. Subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies were obtained before and after the dietary intervention, and at the end of the study period, respectively. MDSA favored the abundance of small adipocytes in WAT. In SAT, the expression of angiogenesis genes increased after MDSA intervention. In VAT, the expression of genes implicated in adipogenesis, angiogenesis, autophagy and fatty acid usage was upregulated. In addition, a higher immunofluorescence staining for PPARG, CD31+ cells and M2-like macrophages and increased ADRB1 and UCP2 protein contents were found compared to controls. Changes in WAT correlated with a significant reduction in circulating inflammatory markers and LDL-cholesterol levels. These results support a protective effect of a Mediterranean diet supplemented with almonds on obesity-related WAT dysfunction.

Prevalence of low skeletal muscle mass following bariatric surgery.

BACKGROUND AND AIMS: Evidence on the occurrence of low skeletal muscle mass (low-SMM) following bariatric surgery (BS) as well as on the impact of low-SMM antedating BS on post-surgical body composition (BC) are scant. In this context, we aimed to prospectively evaluate the prevalence of low-SMM prior to and up to 5 years after BS, and to evaluate pre-surgical low-SMM as an independent risk factor for the presence of low-SMM after BS. METHODS: Retrospective analysis of prospectively collected database. BC was assessed by bioelectrical impedance analysis (BIA). A BIA-based formula was used to calculate skeletal muscle mass (SMM). Class I and class II low-SMM were defined respectively as a SMM index (SMMI = SMM/height2) value between -1 and -2, or > -2 standard deviations from the gender-specific regression line of the BMI versus the SMMI relationship in our reference group. RESULTS: A total 952 subjects were included, with BC being available for 877 (92%) subjects at 12 months and for 576 subjects (60%) at 60 months after BS. Prior to surgery, and at 12-, or at 60-months after surgery, class I and class II low-SMM was ascertained respectively in 15.6% and 4.6%, 5.3% and 1.4%, and 16.6% and 6.3% of the study participants. Logistic regression analysis showed that the occurrence of low-SMM at 12- and 60-months follow-up, was independently predicted not only by age at the time of surgery [respectively, HR: 1.052 (95% CI 1.020-1.084), p = 0.001; and 1.042 (95% CI 1.019-1.066); p < 0.001] but also by the presence of low-SMM prior to surgery [respectively, HR: 10.717 (95% CI 5.771-19.904), p < 0.001; and 5.718 (95% CI 3.572-9.153); p < 0.001]. CONCLUSIONS: Our data suggest that a low-SMM phenotype occurs not only in obesity surgery candidates but also after BS, and that low-SMM prior to surgery is an important risk factor for low-SMM throughout post-surgical follow-up.

Effect on gut microbiota of a 1-y lifestyle intervention with Mediterranean diet compared with energy-reduced Mediterranean diet and physical activity promotion: PREDIMED-Plus Study.

BACKGROUND: The Mediterranean diet is a well-recognized healthy diet that has shown to induce positive changes in gut microbiota. Lifestyle changes such as diet along with physical activity could aid in weight loss and improve cardiovascular risk factors. OBJECTIVES: To investigate the effect of an intensive lifestyle weight loss intervention on gut microbiota. METHODS: This is a substudy of the PREDIMED-Plus (Prevención con Dieta Mediterránea-Plus), a randomized controlled trial conducted in overweight/obese men and women (aged 55-75 y) with metabolic syndrome. The intervention group (IG) underwent an intensive weight loss lifestyle intervention based on an energy-restricted Mediterranean diet (MedDiet) and physical activity promotion, and the control group (CG) underwent a non-energy-restricted MedDiet for 1 y. Anthropometric, biochemical, and gut microbial 16S rRNA sequencing data were analyzed at baseline (n = 362) and 1-y follow-up (n = 343). RESULTS: IG participants had a weight loss of 4.2 (IQR, -6.8, -2.5) kg compared with 0.2 (IQR, -2.1, 1.4) kg in the CG (P < 0.001). Reductions in BMI, fasting glucose, glycated hemoglobin, and triglycerides and an increase in HDL cholesterol were greater in IG than in CG participants (P < 0.05). We observed a decrease in Butyricicoccus, Haemophilus, Ruminiclostridium 5, and Eubacterium hallii in the IG compared with the CG. Many genera shifted in the same direction within both intervention groups, indicating an overall effect of the MedDiet. Decreases in Haemophilus, Coprococcus 3, and few other genera were associated with a decrease in adiposity parameters in both intervention groups. Changes in Lachnospiraceae NK4A136 were positively associated with changes in MedDiet adherence. CONCLUSIONS: Weight loss induced by an energy-restricted MedDiet and physical activity induce changes in gut microbiota. The role of MedDiet-induced changes on the host might be via short-chain fatty acid producing bacteria, whereas with energy restriction, these changes might be modulated with other mechanisms, which need to be explored in future studies. This trial was registered at http://www.isrctn.com/ISRCTN89898870 as ISRCT 89898870.

Contribution of ultra-processed foods in visceral fat deposition and other adiposity indicators: Prospective analysis nested in the PREDIMED-Plus trial.

BACKGROUND & AIMS: Ultra-processed food and drink products (UPF) consumption has been associated with obesity and its-related comorbidities. Excess of visceral fat, which appears with increasing age, has been considered as the culprit contributing to adiposity-associated adverse health outcomes. However, none of previous studies elucidated the link between UPF and directly quantified adiposity and its distribution. We aimed to prospectively investigate the association between concurrent changes in UPF consumption and objectively assessed adiposity distribution. METHODS: A subsample of 1485 PREDIMED-Plus participants (Spanish men and women aged 55-75 years with overweight/obesity and metabolic syndrome) underwent body composition measurements. Consumption of UPF at baseline, 6 and 12 months was evaluated using a validated 143-item semi-quantitative Food Frequency Questionnaire. Food items (g/day) were categorized according to their degree of processing using NOVA system. Regional adiposity (visceral fat (in g) and android-to-gynoid fat ratio) and total fat mass (in g) at three time points were measured with dual-energy X-ray absorptiometry (DXA) and were normalized using sex-specific z-scores. The association of changes in UPF consumption, expressed as the percentage of total daily intake (daily g of UPF/total daily g of food and beverage intake∗100), with adiposity changes was evaluated using linear mixed-effects models. RESULTS: On average, the consumption of UPF accounted for 8.11% (SD 7.41%) of total daily intake (in grams) at baseline. In multivariable-adjusted model, 10% daily increment in consumption of UPF was associated with significantly (all p-values <0.05) greater accumulation of visceral fat (ß 0.09 z-scores, 95% CI 0.05; 0.13), android-to-gynoid fat ratio (0.05, 0.00; 0.09) and total fat (0.09, 0.06; 0.13). CONCLUSION: A higher consumption of UPF was associated with greater age-related visceral and overall adiposity accumulation. Further studies are warranted to confirm these results in other populations and settings. 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.

Gut Microbiota Profile and Changes in Body Weight in Elderly Subjects with Overweight/Obesity and Metabolic Syndrome.

Gut microbiota is essential for the development of obesity and related comorbidities. However, studies describing the association between specific bacteria and obesity or weight loss reported discordant results. The present observational study, conducted within the frame of the PREDIMED-Plus clinical trial, aims to assess the association between fecal microbiota, body composition and weight loss, in response to a 12-month lifestyle intervention in a subsample of 372 individuals (age 55-75) with overweight/obesity and metabolic syndrome. Participants were stratified by tertiles of baseline body mass index (BMI) and changes in body weight after 12-month intervention. General assessments, anthropometry and biochemical measurements, and stool samples were collected. 16S amplicon sequencing was performed on bacterial DNA extracted from stool samples and microbiota analyzed. Differential abundance analysis showed an enrichment of Prevotella 9, Lachnospiraceae UCG-001 and Bacteroides, associated with a higher weight loss after 12-month of follow-up, whereas in the cross-sectional analysis, Prevotella 2 and Bacteroides were enriched in the lowest tertile of baseline BMI. Our findings suggest that fecal microbiota plays an important role in the control of body weight, supporting specific genera as potential target in personalized nutrition for obesity management. A more in-depth taxonomic identification method and the need of metabolic information encourages to further investigation.

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.

A Propensity Score Cohort Study on the Long-Term Safety and Efficacy of Sleeve Gastrectomy in Patients Older Than Age 60.

Background: Bariatric surgery (BS) in older obese subjects (>60 years of age) has risen in the past decade and will continue to rise in the coming years due to ageing of the population. Aim: To evaluate the short- (12 months) and long-term (60 months) results of laparoscopic sleeve gastroscopy (LSG) in patients older than age 60. Methods: We performed a retrospective review of patients prospectively included in a database from January 2007 to December 2013. All patients >60 [older group (OG)] who had undergone LSG were included. The control group (CG) included patients aged 50 to 59 years who had undergone LSG during the same period. Results: 116 (8.4 % of total surgery) and 145 patients were included in the OG and CG, respectively. BS in patients >60 years increased from 2.4% in 2003 to 14% in the last 2 years of the study. After inverse probability of treatment weighting (IPTW) analysis, all absolute standardized differences were <0.15. A 60-month follow-up was attained in 90% of patients in the OG and 74% in the CG. There were no significant differences in postoperative complications between the two groups. At 12 and 60 months after LSG, both groups achieved a similar body mass index. There was no statistical difference in the percentage of resolution of type 2 diabetes, hypertension, dyslipidemia, and SAHS between the two groups. In both groups, all the nutritional parameters evaluated remained within the normal range throughout the study. Conclusions: LSG provides acceptable outcomes and is safe in older adults indicating that age should not be a limitation to perform BS in this population.

New Metrics to Assess Type 2 Diabetes After Bariatric Surgery: The "Time-Within-Remission Range".

Almost one third of patients do not achieve type 2 diabetes remission after bariatric surgery or are unable to sustain this effect long term. Our objective was to delve further into the dynamic responses of diabetes after bariatric surgery and to evaluate the "time-within-remission range" as a variable of metabolic control. A descriptive cohort study was done using a computerised multicentre and multidisciplinary registry. All data were adjusted by propensity score. A total of 1186 subjects with a follow-up of 4.5 ± 2.5 years were included. Type of surgery, diabetes remission, recurrence of diabetes, "time-within-remission range" and key predictors of diabetes outcomes were assessed. All patients (70% women, 51.4 ± 9.2 years old, body mass index (BMI) 46.3 ± 6.9 kg/m2) underwent primary bariatric procedures. "Time-within-remission range" were 83.3% (33.3-91.6) after gastric bypass, 68.7% (7.1-87.5) after sleeve gastrectomy and 90% (83.3-92.8) after malabsorptive techniques (p < 0.001 for all). Duration of diabetes, baseline HbA1c and insulin treatment were significantly negatively correlated with the "time-within-remission range". The association of bariatric techniques with "time-within-remission range", using gastric bypass as a reference, were: odds ratio (OR) 3.70 (2.34-5.84), p < 0.001 for malabsorptive techniques and OR 0.55 (0.40-0.75), p < 0.001 for sleeve gastrectomy. Characteristics of type 2 diabetes powerfully influence the outcomes of bariatric surgery. The "time-within-remission range" unveils a superiority of gastric bypass compared to sleeve gastrectomy.