DNA Methylation Remodeling after Bariatric Surgery Correlates with Clinical Parameters.

The altered functions of adipose tissue are one of the main issues in obesity. Bariatric surgery is associated with improvement of obesity associated comorbidities. Here DNA methylation remodeling in adipose tissue after bariatric surgery is examined. After six months postoperative, DNA methylation shows changes in 1155 CpG sites, 66 of these sites correlate with body mass index. Some sites also show correlation with LDL-C, HDL-C, total cholesterol, and triglycerides. CpG sites are located in genes that have not previously been linked to obesity or metabolic diseases. GNAS complex locus is one of those that presented CpG site with the greatest changes after surgery, and the most significant correlation with BMI and lipid profiles. These results show that epigenetic regulation may be involved in the alteration of adipose tissue functions in obesity.

Women with Anemia Refractory to Oral Iron Treatment Following Bariatric Surgery: a Short-Term Analysis.

INTRODUCTION: Iron deficiency and anemia are common after bariatric surgery. Women have a higher risk of developing such long-term complications. Though oral supplementation is indicated, intravenous iron therapy is required in some cases. METHODS: This retrospective study included patients who underwent bariatric surgery between 2012 and 2018. Postoperative anemia patients receiving parental iron therapy were assessed during the first 24 months. Their baseline characteristics, surgery type, and laboratory test results were analyzed. A follow-up analysis included a subgroup of women with and without gynecological disorders. Patients with vitamin B12 or folic acid deficiencies were excluded. RESULTS: Six hundred eleven (63.3%) met the inclusion criteria: 525 underwent gastric bypass, of which 79.6% were women. Overall, postoperative anemia was 28.9% (24.5% related to gastric bypass), especially among women (84%). Anemia refractory to oral iron therapy was observed in 12.9% of patients. All the patients requiring iron infusions (n = 54) were women, and half of them (51.8%) reported abnormal uterine bleeding. Postsurgical hemogram values were significantly lower in patients with abnormal uterine bleeding (despite the same number of infusions) than in those without gynecological disorders; 89.2% of these women had preoperative anemia. CONCLUSION: Anemia is frequent in bariatric surgery patients despite supplementation. Women undergoing gastric bypass with a history of gynecological disorders are prone to require more iron infusions. Consulting with the patient about a higher risk is important, and probably knowing the plan or including the opinion of an OBGYN to determine as a team the assessment, treatment, and prognosis.

DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity.

BACKGROUND: Obesity is accompanied by excess adipose fat storage, which may lead to adipose dysfunction, insulin resistance, and type 2 diabetes (T2D). Currently, the tendency to develop T2D in obesity cannot be explained by genetic variation alone-epigenetic mechanisms, such as DNA methylation, might be involved. Here, we aimed to identify changes in DNA methylation and gene expression in visceral adipose tissue (VAT) that might underlie T2D susceptibility in patients with obesity. METHODS: We investigated DNA methylation and gene expression in VAT biopsies from 19 women with obesity, without (OND = 9) or with T2D (OD = 10). Differences in genome-scale methylation (differentially methylated CpGs [DMCs], false discovery rate < 0.05; and differentially methylated regions [DMRs], p value < 0.05) and gene expression (DEGs, p value <0.05) between groups were assessed. We searched for overlap between altered methylation and expression and the impact of altered DNA methylation on gene expression, using bootstrap Pearson correlation. The relationship of altered DNA methylation to T2D-related traits was also tested. RESULTS: We identified 11 120 DMCs and 96 DMRs distributed across all chromosomes, with the greatest density of epigenomic alterations at the MHC locus. These alterations were found in newly and previously T2D-related genes. Several of these findings were supported by validation and extended multi-ethnic analyses. Of 252 DEGs in the OD group, 68 genes contained DMCs (n = 88), of which 24 demonstrated a significant relationship between gene expression and methylation (p values <0.05). Of these, 16, including ATP11A, LPL and EHD2 also showed a significant correlation with fasting glucose and HbA1c levels. CONCLUSIONS: Our results revealed novel candidate genes related to T2D pathogenesis in obesity. These genes show perturbations in DNA methylation and expression profiles in patients with obesity and diabetes. Methylation profiles were able to discriminate OND from OD individuals; DNA methylation is thus a potential biomarker.

Complications Rate Variability after Bariatric Surgery and the Importance of Standardization of a Reporting System.

BACKGROUND: The rate of early (< 30 days) complications after bariatric surgery has been reported to be 0.4-27.4%. Although the incidence of serious adverse events has decreased with time and experience, controversy regarding how they are reported persists, and the current literature is heterogeneous. METHODS: Data from patients, who underwent primary bariatric surgery (gastric bypass and sleeve gastrectomy) at a single institution between 2012 and 2018, were retrospectively reviewed. Any deviation from a "normal" postoperative course (< 30 days) was identified, and a comparative analysis of early complications according to five models was performed: modified Clavien-Dindo; Longitudinal Assessment of Bariatric Surgery (LABS); Bariatric Surgery Centers of Excellence (BSCOE); American Society for Metabolic and Bariatric Surgery (ASMBS); and Li (major/minor). RESULTS: A total of 788 patients (83.7% gastric bypass), of whom 8.8% deviated from a "normal" postoperative course, were included. After applying the five classifications, the results were as follows: Clavien-Dindo, 8.8%; LABS, 2.3%; BSCOE, 0.4%; ASMBS, 9.9%; and Li, 11.2%. The incidence of major/severe/adverse outcomes were as follows: Clavien-Dindo, 2.4%; LABS, 2.3%; BSCOE, 0.4%; ASMBS, 6.9%; and Li 9.2%. Minor complications were as follows: Clavien-Dindo, 6.5%; ASMBS, 3%; and Li, 2%. There was no mortality. CONCLUSION: Germane heterogeneity was found in reporting of early complications after bariatric surgery. Incidence varied according to classification system applied, and Clavien-Dindo demonstrated accuracy as a reporting model. To avoid bias, standardized reporting should be mandatory, and a more stringent and homogeneous reporting system should be established.

Weight loss before bariatric surgery and its impact on poor versus excellent outcomes at 2 years.

PURPOSE: To identify preoperative factors that influence the outcomes of gastric bypass surgery, in terms of excess weight loss at 24 months. METHODS: This retrospective study included two groups of patients who underwent laparoscopic gastric bypass surgery. Group A (poor outcomes) had ≤ 50%EWL or BMI ≥ 30 kg/m2; group B (excellent outcomes) had ≥ 80%EWL at 24 months. A comparative analysis of demography, anthropometry, comorbidities, and metabolic status was performed. A linear regression model was used to evaluate %EWL association; the number of preoperative and postoperative consultations were also compared. RESULTS: A total of 202 patients completed follow-up; 71 (35.1%) and 78 (38%) had poor and excellent outcomes (%EWL 44.1 ± 9.4% vs. 92 ± 10.9%), respectively. Mean age was 40.4 ± 8.9 years. Patients with poor outcomes had higher weight and BMI, lesser preoperative %EWL, higher dyslipidemia and diabetes rates with longer periods of evolution, and increased HbA1c% levels. In the linear regression analysis, preoperative %EWL and initial and preoperative BMI were statistically significant determinants of %EWL at 24 months Diabetes remission was 46.2% (group A) vs. 66.6% (group B). Group A had higher non-attendance rates after surgery. CONCLUSION: The factors independently associated with greater %EWL at 24 months between groups were higher preoperative %EWL, and lower initial and preoperative BMI.

Long versus short biliopancreatic limb in Roux-en-Y gastric bypass: short-term results of a randomized clinical trial.

BACKGROUND: The Roux-en-Y gastric bypass continues to be one of the most performed bariatric surgeries because of its adequate balance of outcomes, complications, and durability. Recently, the role of the biliopancreatic limb on weight loss and co-morbidity control has gained attention because it seems to have a positive impact based on limb length. OBJECTIVE: To compare results at 12 months of a "standard" (group 1) versus a long (group 2) biliopancreatic limb bypass. Biliopancreatic limbs were 50 cm and 200 cm, and alimentary limbs were 150 cm and 50 cm, respectively. SETTING: Academic Referal Center; Mexico City; Public Seeting. METHODS: Randomized study with patients undergoing both types of surgeries at a single academic center from 2016 to 2018. The analysis included weight loss, co-morbidity control (diabetes and hypertension), biochemical panel, operative outcomes, and complications. RESULTS: Two-hundred ten patients were included (105 in each group). Almost all data were homogenous at baseline. Female sex comprised 86.1% of cases, with a mean body mass index of 43.5 kg/m2. Excess weight loss (77.6 ± 15.7% versus 83.6 ± 16.7%; P = .011) and total weight loss (33.5 ± 6.4% versus 37.1 ± 7.1%; P < .001) was higher in group 2; better HbA1C levels were also observed. Co-morbidity outcomes, operative data, and complications were similar between groups. CONCLUSION: The Roux-en-Y gastric bypass with 200 cm of biliopancreatic limb length induces more weight loss at 12 months than a 50 cm limb length. Better HbA1C levels were also observed, but similar effects on co-morbidities and complications were noted.

Metabolic Surgery and Class 1 Obesity (< 35 kg/m2): a Prospective Study with Short-, Mid-, and Long-term Results Among Latinos.

INTRODUCTION: Metabolic surgery for managing class 1 obesity and type 2 diabetes mellitus has recently gained popularity. The Latino population presents high rates of these diseases. Reports on surgical outcomes in this population are scarce. METHODS: Prospective study with Mexican patients diagnosed with diabetes and class 1 obesity submitted to Roux-en-Y gastric bypass. The objective was to determine short-, mid-, and long-term outcomes (weight loss, metabolic, morbidity, and diabetes remission). Sub-analysis was included, based on preoperative usage of one (group A) or more (group B) oral hypoglycemic agents ± insulin. RESULTS: Fifty-one patients with a mean body mass index of 33.1 ± 1.9 kg/m2, and glycated hemoglobin 7.2 ± 1.7% were included. Significant improvements were observed in almost every parameter. At 24, 36, and 60 months, complete diabetes remission was achieved in 73.8%, 52.2%, and 50% of patients with glycated hemoglobin levels of 5.7% ± 0.8%, 5.8% ± 0.5%, and 6.1% ± 0.8%, respectively. At 24, 36, and 60 months, patients in group A (N=28) showed 90.9%, 69.2%, and 75% remission, respectively, versus patients in group B (N=23), who had remission rates of 50%, 30%, and 25% during the same period. Diabetes relapse was higher in patients using ≥ 2 oral hypoglycemic agents ± insulin before surgery. CONCLUSION: Gastric bypass is a safe and effective metabolic surgery that results in excellent mid- and long-term results among Mexicans. Patients using one drug preoperatively showed improved results and remission rates, which underscores the importance of intervening in the early stages of the disease. TRIAL REGISTRATION: Clinical Trials identifier: NCT04595396 ( www.ClinicalTrials.gov ).

Type 2 Diabetes Mellitus Remission Models Following Laparoscopic Gastric Bypass: a 4-Model Analysis in a Latino Population.

BACKGROUND: Bariatric surgery is indicated for major weight loss and for the control of associated comorbidities, particularly type 2 diabetes. Remission prediction scores have been proposed for this end, such as: DiaRem, Ad-DiaRem, ABCD, and DiaBetter. Nevertheless, they have not been evaluated all together in a specific population. METHODS: Retrospective study with Mexican patients submitted to gastric bypass with at least 12 months follow-up. All patients had BMI > 30 kg/m2 and type 2 diabetes. The primary objective was to evaluate the remission prediction performance of scores. A baseline analysis (anthropometric, biochemical, and metabolic) and remission rates were obtained. Remission scores and cut-off values were assigned based on original descriptions. A ROC analysis was performed for sensibility and specificity. RESULTS: A total of 95 patients were included. Mean age 44 years, 85.6% female with mean BMI of 44.1 kg/m2, and mean HbA1C of 7.2%. At 12 months, complete remission was obtained in 76.8%. ROC curves were plotted showing that DiaRem had 75.3% sensitivity and 68.2% specificity (AUC 0.723 p = 0.001), Ad-DiaRem had 84.9% and 50% (AUC 0.702 p = 0.002), ABCD had 57.5% and 77.3% (AUC 0.0.690 p = 0.002), and DiaBetter had 72.6% and 77.3% (AUC 0.748 p < 0.001). CONCLUSION: In Mexican patients with obesity and type 2 Diabetes, submitted to gastric bypass, remission prediction could be assessed with any current model showing satisfactory sensibility and specificity. Among such models, DiaBetter obtained the best statistical performance in our population. Type 2 diabetes remission rate at 1 year is similar to any other race or ethnicity.

Unexpected Intraoperative Findings, Situations, and Complications in Bariatric Surgery.

BACKGROUND: Bariatric surgery is considered a safe therapy to treat obesity. Postoperative complications are well known; however, there is a lack of data describing intraoperative complications and/or unexpected findings, and if there is further impact on outcomes. METHODS: Retrospective study with patients operated between 2013 and 2016 at a single institution. All operative information was collected prospectively and aimed to analyze the incidence and causes of unexpected intraoperative findings, complications, change in surgical plan, extra surgeries, and procedure interruption in patients submitted to bariatric surgery. Secondarily, a morbidity analysis was performed, correlating intraoperative complications with postoperative complications and length of stay. RESULTS: Four-hundred and five patients were included. Female sex comprised 82% of cases, and a median age of 38 years old was observed; almost 90% were gastric bypass. In 29.3% of cases, there were intraoperative findings, mainly adhesions, abdominal wall hernias, positive methylene blue test, hiatal hernias, and gastrointestinal stromal tumors. Associated surgeries were performed in 8.6% cases, and intraoperative adverse events reported in 7.1%, where organ injury and anastomosis problems were the most frequent. A change in the operative plan was done in 0.9% and surgery interruption in 1.2% of the cases. Early complications were observed in 6.6%. There was no correlation between intraoperative complications and length of stay or early complications. CONCLUSION: Unexpected intraoperative findings/complications are common in bariatric surgery, but without increasing morbidity or length of stay. Surgery suspension, change in the planned technique, or adding extra (non-bariatric) procedures may occur.

Depression Before and After Bariatric Surgery in Low-Income Patients: the Utility of the Beck Depression Inventory.

BACKGROUND: The prevalence of psychological disorders in bariatric surgery candidates is well established, where anxiety and depression are commonly observed. Depression prevalence and evolution after gastric bypass, and its impact on weight loss, have been less explored, especially among low-income patients. METHODS: A retrospective study with low-income patients undergoing bariatric surgery from 2015 to 2016. A comparative analysis of preoperative depression (the Beck Depression Inventory II) was performed and compared at 6 and 12 months. A demographic and weight loss analysis was also performed. RESULTS: Seventy-three patients were included. Female sex comprised 76.7% of cases, and baseline depression was present in 45.2%, being severe in 2.7%. The analysis at 6 months showed Beck's score improvement (12.3 baseline vs. 4.2 points at 6 months, p = 0.006), as well as for individual items (excepting irritability). At 12 months, the mean score was 5 points, without difference vs. 6 months. At 6 and 12 months, depression (any degree) was present in 9.6 and 8.6%, corresponding to percentage change rates of - 65.8 and - 59.3%. Only one patient (2.7%) presented severe depression. Depression status before surgery had no influence in weight loss amount at 12 months. CONCLUSION: Almost half of bariatric surgery candidates have some degree of depression that improves dramatically soon after bariatric surgery. Such change continues stable during the first year. Improvement was independent of gender, and depression has no influence on weight loss. In low-income bariatric patients, depression is lower than reports from developed countries, but similar improvement has been observed.

The Impact of Preoperative BMI (Obesity Class I, II, and III) on the 12-Month Evolution of Patients Undergoing Laparoscopic Gastric Bypass.

BACKGROUND: Whether or not the initial body mass index (BMI) influences weight loss and comorbidities improvement after bariatric surgery continues to be a matter of debate. The main reason for this is a lack of studies including obesity class I. METHODS: Retrospective study with patients submitted to gastric bypass at a single institution. They were classified based on initial BMI (obesity class I, II, and III), and a comparative analysis of their metabolic profile (glucose, HbA1c%, C-peptide, insulin and diabetes medication), lipid profile (triglycerides, total cholesterol, HDL, LDL), and clinical data (systolic/diastolic blood pressure and cardiovascular risk) was performed at 0 and 12 months. Diabetes remission and weight loss were also analyzed. RESULTS: Two-hundred and twenty patients were included (23 in group 1, 113 in group 2, and 84 in group 3). Initial weight, BMI, and number of patients with T2DM were statistically different in group 1; other parameters were homogenous. At 12 months, every group had similar improvement of the metabolic profile, excepting serum insulin. Diabetes remission was 57.9, 61.1, and 60% for group 1, 2, and 3. For weight loss, there were differences between groups when using BMI and percentage of excess weight loss, but not with percentage of total weight loss. The non-metabolic and clinical data improved without differences, except for total cholesterol and LDL. CONCLUSIONS: The metabolic, lipid, and clinical profiles associated with obesity present similar improvement 1 year after laparoscopic gastric bypass, despite different baseline BMI. Diabetes remission and percentage of total weight loss were also similar.

Metabolic syndrome 2 years after laparoscopic gastric bypass.

BACKGROUND: The latest diabetes consensus identified obesity as key component of the metabolic syndrome. The role of bariatric surgery over such syndrome has been less explored with a lack of long term studies, and especially among Mexicans. METHODS: Retrospective study including patients with metabolic syndrome submitted to laparoscopic gastric bypass at a single institution with complete data after 24 months. The objective was to analyze the improvement of the syndrome and each component. Demographic, anthropometric, biochemical and clinical parameters were analyzed at 12 and 24 months. Secondarily weight loss and other parameters were also analyzed. Finally, an analysis of syndrome improvement related to weight loss was performed. RESULTS: Sixty-three patients were included. The 2 most common components associated with obesity were reduced HDL and raised glucose or Type 2 diabetes. There was a significant improvement of metabolic syndrome and its components, as well as for the rest of the analyzed data, from the first check point and throughout follow-up. Prevalence of such syndrome was 6.3% at 12 and 24 months. Hypertension and raised glucose or Type 2 diabetes were the components with the greatest and fastest improvement; HDL levels and obesity were the least improved. There was a direct relationship between percentage of excess weight loss or percentage of excess BMI loss, and syndrome's improvement. CONCLUSION: Patients with metabolic syndrome improved after gastric bypass, with results lasting after 2 years; other metabolic parameters important for cardiovascular risk were also positively affected. There was a relationship between the amount of weight loss and improvement of metabolic syndrome.

Type 2 diabetes mellitus outcomes after laparoscopic gastric bypass in patients with BMI <35 kg/m2 using strict remission criteria: early outcomes of a prospective study among Mexicans.

BACKGROUND: Mild obesity (BMI 30-34.9 kg/m2) is highly prevalent worldwide and is associated with type 2 diabetes mellitus. The efficacy of bariatric surgery remains unclear, including among Mexicans. The criteria for diabetes remission are inconsistent, as they are based on different thresholds for glycated hemoglobin, with remission rates ranging from 43 to 73%. METHODS: Mildly obese patients with type 2 diabetes mellitus who underwent laparoscopic gastric bypass were prospectively analyzed. The primary objective was to determine the impact of surgery on their metabolic profiles. Demographic, clinical, and biochemical parameters were measured at baseline and at 3, 6, 9, 12, and 18 months. Diabetes remission rate was defined as an HbA1c <5.7%. Complications within 30 days and weight loss (% total weight loss) were also analyzed. RESULTS: Twenty-three Mexican patients underwent surgery. Of the 19 patients, evaluable at 18 months, nine (47.4%) achieved complete diabetes remission, seven (36.8%) showed partial remission, and three (15.8%) showed improvement. Significant improvements in lipid profile, cardiovascular risk, blood pressure, and every metabolic parameter were observed, beginning at the first month and throughout the study. The final total percentage weight loss was 24.9%. Three patients (13%) experienced complications, but none required reoperation or died. CONCLUSION: Laparoscopic gastric bypass is a safe and effective method to improve the metabolic profile of mildly obese Mexican patients with type 2 diabetes mellitus, inducing high remission rates even when the strictest model is used.

A Prospective Study of the Conservative Management of Asymptomatic Preoperative and Postoperative Gallbladder Disease in Bariatric Surgery.

INTRODUCTION: Bariatric surgery is the most effective therapy for weight loss in patients with morbid obesity. One of the most common long-term complications includes cholelithiasis. There is not a clear consensus in how to treat an asymptomatic gallbladder disease before and after bariatric surgery. METHODS: Prospective study with every patient submitted to bariatric surgery from 2012 to 2014. The gallbladder status was assessed with an ultrasound before and after surgery (12 months), and a conservative management was conducted for patients with asymptomatic disease (preoperative and de novo); the need for delayed cholecystectomy was reported. Secondarily, an analysis of weight loss (%EWL) and gallbladder status was performed. RESULTS: Two-hundred and two bariatric surgeries were performed. The global incidence of preoperative gallbladder disease was 34.3 %, with 14.2 % presenting sludge, 20.1 % asymptomatic gallstones, and 2.3 % symptomatic gallstones. The final analysis was based on 146 patients; female sex comprised 81.1 % of cases with a mean age of 38.5 years. After 12 months, de novo gallbladder disease was observed in 21.2 %. The overall rate of cholecystectomy because of symptomatic disease after 12 months was 3.4 % (2 % developed acute cholecystitis). There were no differences in %EWL between patients with de novo gallbladder disease and those without. CONCLUSION: Conservative management of asymptomatic gallbladder disease in candidates to bariatric surgery is safe and can be offered in every case, based on the low percentage of patients requiring further cholecystectomy after 12 months. Also, a conservative management can be offered to patients developing de novo sludge/cholelithiasis without related symptoms.

Taste and Olfactory Changes Following Laparoscopic Gastric Bypass and Sleeve Gastrectomy.

BACKGROUND: Alterations in taste/smell after bariatric surgery have been observed, but few data is available. Some authors documented these changes and their role on weight loss but there is no evidence after laparoscopic sleeve gastrectomy (LSG). METHODS: Cohort study with patients submitted to laparoscopic gastric bypass (LGBP) and LSG that were asked to participate in a validated survey. The primary objective was to determinate the differences between procedures for taste and smell changes; a demographic and anthropometric analysis were also performed. Secondarily, the relation between food aversion and weight loss was also obtained. RESULTS: Final analysis was based on 154 patients (104 LGBP and 50 LSG). The overall mean time between surgery and questionnaire was 10 ± 6.7 months. Most of the patients (87.6 %) experienced some taste/smell change. There were no differences between procedures for any change, taste or smell change. More patients submitted to LGBP referred that food smelled different (51.9 vs 34 % for the LSG group; p = 0.040). Higher %EWL was observed for patients presenting food aversion (73.3 ± 19.7 vs 65.8 ± 19.4 % for those without aversion; p = 0.046). Based on type of surgery, the LGBP group had the same trend (%EWL of 78.2 ± 17.3 vs 70.4 ± 18.6 % for those without aversion; p = 0.044). CONCLUSION: The majority of patients presented taste and olfactory changes soon after surgery independently of type of procedure. Patients submitted to LGBP referred more often a different smell in food. Higher %EWL was observed in patients presenting any food aversion, especially in the LGBP group.