A Predictive Tool Based on DNA Methylation Data for Personalized Weight Loss through Different Dietary Strategies: A Pilot Study.

BACKGROUND AND AIMS: Obesity is a public health problem. The usual treatment is a reduction in calorie intake and an increase in energy expenditure, but not all individuals respond equally to these treatments. Epigenetics could be a factor that contributes to this heterogeneity. The aim of this research was to determine the association between DNA methylation at baseline and the percentage of BMI loss (%BMIL) after two dietary interventions, in order to design a prediction model to evaluate %BMIL based on methylation data. METHODS AND RESULTS: Spanish participants with overweight or obesity (n = 306) were randomly assigned to two lifestyle interventions with hypocaloric diets: one moderately high in protein (MHP) and the other low in fat (LF) for 4 months (Obekit study; ClinicalTrials.gov ID: NCT02737267). Basal DNA methylation was analyzed in white blood cells using the Infinium MethylationEPIC array. After identifying those methylation sites associated with %BMIL (p < 0.05 and SD > 0.1), two weighted methylation sub-scores were constructed for each diet: 15 CpGs were used for the MHP diet and 11 CpGs for the LF diet. Afterwards, a total methylation score was made by subtracting the previous sub-scores. These data were used to design a prediction model for %BMIL through a linear mixed effect model with the interaction between diet and total score. CONCLUSION: Overall, DNA methylation predicts the %BMIL of two 4-month hypocaloric diets and was able to determine which type of diet is the most appropriate for each individual. The results of this pioneer study confirm that epigenetic biomarkers may be further used for precision nutrition and the design of personalized dietary strategies against obesity.

Effects of individualized dietary counseling on nutritional status and quality of life in post-discharge patients after surgery for gastric cancer: A randomized clinical trial.

Background: Currently, the supporting evidence for dietary counseling is insufficient. The aim of this study is to evaluate the impact of individualized dietary counseling on nutritional outcomes and quality of life (QOL) in patients undergoing surgery for gastric cancer. Methods: This study was a prospective, single-center, randomized controlled trial. The patients after surgery for gastric cancer were randomly assigned (1:1) to the intervention group and the control group. In the intervention group, patients receive individualized dietary counseling based on individual calorie needs and symptom assessment at 24 h before discharge, 14, 21, 30, and 60 days postoperatively. Patients in the control group received routine dietary counseling. The primary endpoint was body mass index (BMI) loss at 30, 60, and 90 days after surgery; the secondary endpoints were calorie and protein intake at 30 and 60 days after surgery, blood parameters, the 90-day readmission rate, and QOL at 90 days after surgery. Results: One hundred thirty patients were enrolled; 67 patients were assigned to the intervention group and 63 patients to the control group. Compared with the control group, patients in the intervention group were significantly less BMI loss at 30 days (-0.84 ± 0.65 vs. -1.29 ± 0.83), 60 days (-1.29 ± 0.92 vs. -1.77 ± 1.13), and 90 days (-1.37 ± 1.05 vs. -1.92 ± 1.66) after surgery (all P< 0.05). Subgroups analysis by surgery type showed that the intervention could significantly reduce BMI loss in patients undergoing total and proximal gastrectomy at 30 days (-0.75 ± 0.47 vs. -1.55 ± 1.10), 60 days (-1.59 ± 1.02 vs. -2.55 ± 1.16), and 90 days (-1.44 ± 1.19 vs. -3.26 ± 1.46) after surgery (all P< 0.05). At 60 days after surgery, calorie goals were reached in 35 patients (77.8%) in the intervention group and 14 patients (40.0%) in the control group (P = 0.001), and protein goals were reached in 40 patients (88.9%) in the intervention group and 17 patients (48.6%) in the control group (P< 0.001). Regarding the QOL at 90 days after surgery, the patients in the intervention group had a significantly lower level of fatigue, shortness of breath and stomach pain, better physical function, and cognitive function (P< 0.05). Conclusions: Post-discharge individualized dietary counseling is an effective intervention to reduce post-gastrectomy patient weight loss and to elevate calorie intake, protein intake, and QOL.

A weight-loss model based on baseline microbiota and genetic scores for selection of dietary treatments in overweight and obese population.

BACKGROUND & AIMS: The response to weight loss depends on the interindividual variability of determinants such as gut microbiota and genetics. The aim of this investigation was to develop an integrative model using microbiota and genetic information to prescribe the most suitable diet for a successful weight loss in individuals with excess of body weight. METHODS: A total of 190 Spanish overweight and obese participants were randomly assigned to two hypocaloric diets for 4 months: 61 women and 29 men followed a moderately high protein (MHP) diet, and 72 women and 28 men followed a low fat (LF) diet. Baseline fecal DNA was sequenced and used for the construction of four microbiota subscores associated with the percentage of BMI loss for each diet (MHP and LF) and for each sex. Bootstrapping techniques and multiple linear regression models were used for the selection of families, genera and species included in the subscores. Finally, two total microbiota scores were generated for each sex. Two genetic subscores previously reported to weight loss were used to generate a total genetic score. In an attempt to personalize the weight loss prescription, several linear mixed models that included interaction with diet between microbiota scores and genetic scores for both, men and women, were studied. RESULTS: The microbiota subscore for the women who followed the MHP-diet included Coprococcus, Dorea, Flavonifractor, Ruminococcus albus and Clostridium bolteaea. For LF-diet women, Cytophagaceae, Catabacteriaceae, Flammeovirgaceae, Rhodobacteriaceae, Clostridium-x1vb, Bacteriodes nordiiay, Alistipes senegalensis, Blautia wexlerae and Psedoflavonifractor phocaeensis. For MHP-diet men, Cytophagaceae, Acidaminococcaceae, Marinilabiliaceae, Bacteroidaceae, Fusicatenibacter, Odoribacter and Ruminococcus faecis; and for LF-men, Porphyromanadaceae, Intestinimonas, Bacteroides finegoldii and Clostridium bartlettii. The mixed models with microbiota scores facilitated the selection of diet in 72% of women and in 84% of men. The model including genetic information allows to select the type of diet in 84% and 73%, respectively. CONCLUSIONS: Decision algorithm models can help to select the most adequate type of weight loss diet according to microbiota and genetic information. CLINICAL TRIAL REGISTRY NUMBER: This trial was registered at www. CLINICALTRIALS: gov as NCT02737267 (https://clinicaltrials.gov/ct2/show/NCT02737267?term=NCT02737267&cond=obekit&draw=2&rank=1).

Histopathologic findings on removed stomach after sleeve gastrectomy. Do they influence the outcome?

Little is known about the role of chronic gastritis on weight loss after laparoscopic sleeve gastrectomy (LSG). This study aims to investigate the relationship between histopathologic findings of gastric specimens, excess weight loss (% EWL), and excess BMI loss (% EBL) at 6 and 12 months follow up after LSG. We retrospectively reviewed the clinical records of 95 patients who had undergone LSG between January 2017 and December 2019. Based on the histopathological findings of gastric resection specimens, patients were divided into those with chronic gastritis (CG) and those without chronic gastritis (NoCG) and compared for their % EWL and % EBL at 6 and 12 months. The mean BMI was 44.74 kg/m2 in the CG group and 44.14 kg/m2 in the NoCG group. At 6 months follow up, the CG group had a mean % EWL of 45.7 and % EBL of 40.5, while NoCG had a mean % EWL of 51.1 and % EBL of 46.7. After 1-year follow-up, the CG group had a mean % EWL of 53.1 and a % EBL of 44.8, while the NoCG group had a % EWL of 54.1 and % EBL of 44. This observational study does not support the hypothesis that the occurrence of chronic gastritis can affect postoperative % EWL and % EBL.

Long-term improvement of dyslipidaemia, hyperuricemia and metabolic syndrome in patients undergoing laparoscopic sleeve gastrectomy.

OBJECTIVE: The aim of the study was to assess the long-term impact of laparoscopic sleeve gastrectomy (LSG) on lipid profile, uric acid level and metabolic syndrome. METHODS: A prospective study was performed between 2009-2014, evaluating long-term percentage of excesso body mass index loss (%EBMIL), lipid profile, uric acid level and metabolic syndrome. RESULTS: Overall sixty subjects were followed-up. %EBMIL increased significantly, reaching a maximum (86,9 ± 6,3%) at 5 years post-LSG. Therapeutic success rate (%EBMIL ≥ 60%) was 80% at 5 years. The triglyceride level decreased significantly (148 ± 72.1 mg/dL baseline vs 130.7 ± 57.5 mg/dL at 1 month vs 110.7 ± 42.6 mg/dL at 3 months vs 92.5 ± 35.2 mg/dL at 1 year vs 84.2 ± 32.3 mg/dL at 5 years; p < 0.05 for all). HDL-cholesterol increased and uric acid decreased significantly in the first year postoperatively, remaining stable afterwards (46.9 ± 12.3 mg/dL baseline vs 47.4 ± 10 mg/dL at 1 month vs 49.8 ± 9.3 mg/dL at 3 months vs 55.4 ± 10.2 mg/dL at 1 year; p < 0.05 for all for HDL-cholesterol and 6.4 ± 2 mg/dL baseline vs 6 ± 1.7 mg/dL at 1 month vs 5.2 ± 1.3 mg/dL at 3 months vs 4.8 ± 1 mg/dL at 1 year; p < 0.05 for all for uric acid). The prevalence of metabolic syndrome decreased from 66.7% baseline to 8.3% at 5 years postoperatively (p < 0.01). CONCLUSION: LSG was effective in terms of %EBMIL and metabolic traits improvement for Romanian patients.

Long-term improvement of dyslipidaemia, hyperuricemia and metabolic syndrome in patients undergoing laparoscopic sleeve gastrectomy

ABSTRACT Objective The aim of the study was to assess the long-term impact of laparoscopic sleeve gastrectomy (LSG) on lipid profile, uric acid level and metabolic syndrome. Materials and methods A prospective study was performed between 2009-2014, evaluating long-term percentage of excesso body mass index loss (%EBMIL), lipid profile, uric acid level and metabolic syndrome. Results Overall sixty subjects were followed-up. %EBMIL increased significantly, reaching a maximum (86,9 ± 6,3%) at 5 years post-LSG. Therapeutic success rate (%EBMIL ≥ 60%) was 80% at 5 years. The triglyceride level decreased significantly (148 ± 72.1 mg/dL baseline vs 130.7 ± 57.5 mg/dL at 1 month vs 110.7 ± 42.6 mg/dL at 3 months vs 92.5 ± 35.2 mg/dL at 1 year vs 84.2 ± 32.3 mg/dL at 5 years; p < 0.05 for all). HDL-cholesterol increased and uric acid decreased significantly in the first year postoperatively, remaining stable afterwards (46.9 ± 12.3 mg/dL baseline vs 47.4 ± 10 mg/dL at 1 month vs 49.8 ± 9.3 mg/dL at 3 months vs 55.4 ± 10.2 mg/dL at 1 year; p < 0.05 for all for HDL-cholesterol and 6.4 ± 2 mg/dL baseline vs 6 ± 1.7 mg/dL at 1 month vs 5.2 ± 1.3 mg/dL at 3 months vs 4.8 ± 1 mg/dL at 1 year; p < 0.05 for all for uric acid). The prevalence of metabolic syndrome decreased from 66.7% baseline to 8.3% at 5 years postoperatively (p < 0.01). Conclusions LSG was effective in terms of %EBMIL and metabolic traits improvement for Romanian patients.

Lifestyle Intervention on Body Weight and Physical Activity in Patients with Breast Cancer can reduce the Risk of Death in Obese Women: The EMILI Study.

: Background obesity and sedentary lifestyle have been shown to negatively affect survival in breast cancer (BC). The purpose of this study was to test the efficacy of a lifestyle intervention on body mass index (BMI) and physical activity (PA) levels among BC survivors in Modena, Italy, in order to show an outcome improvement in obese and overweight patients. METHODS: This study is a single-arm experimental design, conducted between November 2009 and May 2016 on 430 women affected by BC. Weight, BMI, and PA were assessed at baseline, at 12 months, and at the end of the study. Survival curves were estimated among normal, overweight, and obese patients. RESULTS: Mean BMI decreased from baseline to the end of the study was equal to 2.9% (p = 0.065) in overweight patients and 3.3% in obese patients (p = 0.048). Mean PA increase from baseline to the end of the study was equal to 125% (p < 0.001) in normal patients, 200% (p < 0.001) in overweight patients and 100% (p < 0.001) in obese patients. After 70 months of follow-up, the 5-year overall survival (OS) rate was 96%, 96%, and 93%, respectively in normal, obese, and overweight patients. Overweight patients had significantly worse OS than normal ones (HR = 3.69, 95%CI = 1.82-4.53 p = 0.027) whereas no statistically significant differences were seen between obese and normal patients (HR 2.45, 95%CI = 0.68-8.78, p = 0.169). CONCLUSIONS: A lifestyle intervention can lead to clinically meaningful weight loss and increase PA in patients with BC. These results could contribute to improving the OS in obese patients compared to overweight ones.

The Relationship Between Histopathologic Findings and Weight Loss in Laparoscopic Sleeve Gastrectomy.

AIM: The aim of this study was to investigate the correlation between histopathologic findings detected in laparoscopic sleeve gastrectomy (LSG) specimens and excess weight loss percentages (%EWL) and excess BMI decrease percentages (%EBL). METHODS: Patients who underwent LSG in the hospital's Gastroenterological Surgery Department between the years 2013 and 2018 and who completed 1 year of follow-up were involved in the study. Patients whose 6th month and 12th month BMI were unknown were excluded from the study. Clinical and pathologic data of the cases were obtained from the automation system of the hospital. RESULTS: As a result of comparison among diagnosis groups, it was detected in the histopathologic analysis that the 12th month mean %EWL measurement was higher in the inactive stomach diagnosis group. In the comparisons among intestinal metaplasia (IM) groups, it was seen that 6th month %EWL and %EBL and 12th month %EWL and %EBL measurements were higher in the group without IM. Age, baseline BMI and active gastritis incidence in histopathologic analysis have a negative effect on weight loss. CONCLUSIONS: A correlation of histopathologic changes in morbid obese patients with weight loss after bariatric surgery was asserted in this study. Operating on younger patients with lower BMI and inactive gastritis with the LSG method could contribute to achieving more successful results. Prospective research studies are necessary within this context.

ANGPTL-4 is Associated with Obesity and Lipid Profile in Children and Adolescents.

Angiopoietin-like protein 4 (ANGPTL-4) regulates lipidic metabolism and affects energy homeostasis. However, its function in children with obesity remains unknown. We investigated plasma ANGPTL-4 levels in children and its relationship with body mass index (BMI) and different lipidic parameters such as free fatty acids (FFA). Plasma ANGPTL-4 levels were analyzed in two different cohorts. In the first cohort (n = 150, age 3-17 years), which included children with normal weight or obesity, we performed a cross-sectional study. In the second cohort, which included only children with obesity (n = 20, age 5-18 years) followed up for two years after an intervention for weight loss, in which we performed a longitudinal study measuring ANGPTL-4 before and after BMI-loss. In the cross-sectional study, circulating ANGPTL-4 levels were lower in children with obesity than in those with normal weight. Moreover, ANGPTL-4 presented a negative correlation with BMI, waist circumference, weight, insulin, homeostasis model assessment of insulin resistance index (HOMA index), triglycerides, and leptin, and a positive correlation with FFA and vitamin-D. In the longitudinal study, the percent change in plasma ANGPTL-4 was correlated with the percent change in FFA, total-cholesterol and high-density lipoprotein cholesterol. This study reveals a significant association of ANGPTL-4 with pediatric obesity and plasma lipid profile.

Prognostic significance of combined pretreatment body mass index (BMI) and BMI loss in patients with esophageal cancer.

Background: Body mass index (BMI) has been associated with a risk of esophageal cancer. However, the influence of BMI and BMI loss on people with esophageal cancer that were treated with different therapies has not been described in China. Methods: In total, 615 consecutive patients that underwent esophagectomy and/or chemotherapy/radiotherapy were classified according to the Asian-specific BMI (kg/m2) cutoff values. The impact of BMI and BMI loss on long-term overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. Results: Multivariate analysis showed that overweight and obese patients had a more favorable survival than normal weight and underweight patients (p=0.017). Patients with a low BMI and high BMI loss before therapy had worse OS than others (p=0.001). Subgroup analysis showed that patients with a high BMI were more likely to suffer hypertension (p<0.001) and receive only surgery (p<0.001), and they were less likely to be smokers (p=0.007) and anemic (p<0.001). Conversely, patients with high BMI loss were more likely to be anemic (p=0.001), to have advanced pathological stage (p=0.012), and to receive chemotherapy and radiotherapy (p=0.001). Moreover, the mortality rate was higher when patients had a high BMI loss. There is no survival benefit of higher BMI in the non-esophageal squamous cell carcinoma (ESCC) group. Conclusion: Pretreatment BMI was an independent prognostic factor for long-term survival in esophageal cancer patients treated with different treatments. The overall survival was increased in esophageal cancer patients with a high pretreatment BMI and no BMI loss. There is no survival benefit of higher BMI in the non-ESCC group.

Revisional Roux-en-Y Gastric Bypass: a Safe Surgical Opportunity? Results of a Case-Matched Study.

OBJECTIVE: To evaluate the safety and efficacy of revisional Roux-en-Y gastric bypass (RYGB) after adjustable gastric banding (AGB) or sleeve gastrectomy (SG) compared with primary RYGB, in regard to early and late morbidity, weight, and resolution of obesity-related comorbidities. METHODS: The group of patients undergoing revisional RYGB was matched in a 1:1 ratio with control patient who underwent a primary RYGB, based on age, gender, American Society of Anesthesiologist (ASA) score, preoperative body mass index (BMI), and diabetes mellitus. Demographics, anthropometrics, preoperative work-up, and perioperative data were retrieved. RESULTS: One hundred fifteen patients (16 males and 99 females) with a mean age of 45.5 ± 1.5 years underwent revisional RYGB following either LAGB in 82 patients (71.3%) or laparoscopic sleeve gastrectomy (LSG) in 33 patients (28.7%). There was no conversion and no mortality in either group. Revisional RYGB was associated with similar early (16.5 vs 15.6%, ns) and late (42.6% vs 32.2%, ns) morbidity rates with a mean follow-up of 25.3 ± 16.6 months compared to primary laparoscopic Roux-en-Y gastric bypass. The revisional RYGB group had significantly less weight loss (mean %EWL 67.4 ± 20.7 vs 72.7 ± 22.9, p = 0.023 and mean %EBMI 68.1 ± 22 vs 78.3 ± 25.7, p = 0.01) at the time of 1 year. Improvement of comorbidities including hypertension (62.5 vs 70.5%; p > 0.05), diabetes (73.7 vs 79%; p > 0.05), and obstructive sleep apnea syndrome (100 vs 97%; p > 0.05) was similar. CONCLUSION: This large case-matched study suggests that conversion of SG or AGB to RYGB is feasible with early and late comparable morbidity in an accredited center; even weight results might be inferior.

A Retrospective Comparative Study of Primary Versus Revisional Roux-en-Y Gastric Bypass: Long-Term Results.

AIMS: To compare the perioperative parameters and excess weight loss between patients operated by laporoscopic Roux-en-Y gastric bypass (LRYGB), as a primary operation or a revisional, for insufficient weight loss after vertical banded gastroplasty (VBG) or adjustable gastric banding (AGB). METHODS: A retrospective analysis of all patients who underwent a LRYGB was performed for the period 2004-2011. Demographics, preoperative body mass index (BMI), co-morbidities, operation time, conversion rate, perioperative complications, hospitalization period, and % of excess BMI loss (%EBMIL) were investigated and compared between groups. RESULTS: Three hundred forty-two laparoscopic gastric bypass operations were performed, 245 were primary, and 97 revisional. Median follow-up was 30 months (range 0-108 months). Mean BMI (kg/m2) before bypass was 45.2 for primary laparoscopic Roux-en-Y gastric bypass (pLRYGB) and 41.1 for revisional laparoscopic Roux-en-Y gastric bypass (rLRYGB). Median operative time and length of stay were longer for rLRYGB 157.5 versus 235 min (p < 0.001) and 6 versus 6.5 days (p = 0.05). Conversion to laparotomy was performed in eight patients, 0.4% of primary and 7.2% of revisional. Morbidity rate was 6.5% in pLRYGB versus 10% in rLRYGB (NS). There was one death in the primary group. Percentage of EBMIL was significantly lower in the revisional group at 12, 18, and 24 months of follow-up. CONCLUSIONS: Revisional and primary gastric bypass have no statistical differences in terms of morbidity. The % of excess BMI loss is lower after revisional gastric bypass during the first 2 years of follow-up. The trend of weight loss or weight regain was similar in both groups.