Association of Bariatric Surgery and Risk of Cancer in Patients With Morbid Obesity.

OBJECTIVE: This study investigates the rates of obesity-related cancers in patients undergoing vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), or no surgical intervention. SUMMARY BACKGROUND DATA: Obesity has been previously associated with increased rates of cancers; however, weight loss surgeries have not been explored to demonstrate their potential risk reduction impact. METHODS: Patients meeting bariatric eligibility criteria between January 2010 and December 2018 were identified. Exact 1:1:1 matching based on baseline patient demographics and comorbidities was used to create 3 groups with identical covariates: patients undergoing VSG, RYGB, and no surgery. RESULTS: A total of 28, bariatric-eligible patients equally split into patients undergoing VSG (n = 9636, 33.3%), RYGB (n = 9636, 33.3%), and those with no surgical intervention (n = 9636, 33.3%). Bariatric-eligible patients that did not undergo surgical intervention had significantly higher rates and odds of developing numerous cancer types included in our study when compared to either surgical cohorts, with any cancer type (4.61%), uterine (0.86%), colorectal (0.57%), and lung cancers (0.50%) being most common. Individuals undergoing RYGB were significantly less likely to develop colorectal cancer compared to patients without any surgical intervention [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.30-0.75]. Additionally, those undergoing VSG were significantly less likely to develop lung cancer than the bariatric eligible no surgery cohort (OR 0.42, 95% CI 0.25-0.70). CONCLUSION: Postoperative rates of any cancer type, lung, ovarian, and uterine cancer were significantly lower in obese patients undergoing either vertical sleeve gastrectomy (VSG) or RYGB compared to bariatric-eligible patients without any surgical intervention.

Determining changes in bone metabolism after bariatric surgery in postmenopausal women.

BACKGROUND: Accelerated bone loss is a known complication after bariatric surgery. Bone mineral density has been shown to decrease significantly after Laparoscopic Roux-en-Y gastric bypass (RYGB). Laparoscopic sleeve gastrectomy (SG) effects on bone density are largely unknown. This should be considered for those with increased preoperative risk for bone loss, such as postmenopausal females. METHODS: This prospective clinical trial included postmenopausal patients, with BMI ≥ 35 k/m2, being evaluated for either RYGB or SG. Patients with history of osteoporosis, estrogen hormone replacement therapy, active smoking, glucocorticoid use, or weight > 295 lb were excluded. Patients underwent DEXA scans preoperatively and 1 year postoperatively with measurement of total body bone mineral density (BMD) and bone mineral content (BMC) as well as regional site-specific BMD and BMC. RESULTS: A total of 28 patients were enrolled. 16 (57.1%) patients underwent RYGB and 12 (42.9%) patients underwent SG. Median preoperative BMI was 44.2 k/m2 (IQR 39.9, 46.6). Median change in BMI at 12 months was - 11.3 k/m2 (IQR - 12.8, - 7.9). A significant reduction in total body BMC was seen when comparing preoperative measurements to postoperative measurements (2358.32 vs 2280.68 grams; p = 0.002). Regional site BMC and BMD significantly decreased in the ribs and spine postoperatively (p = < 0.02) representing the greatest loss in the axial skeleton. Comparing those who underwent RYGB to SG there was no significant difference between the two groups when evaluating changes in total or regional site BMD. CONCLUSION: Postmenopausal women were found to have decreased BMD and BMC after RYGB and SG, suggesting that high-risk women may benefit from postoperative DEXA screening. Further study is needed to determine the clinical significance of these findings. It is unknown if these changes in BMD are due to modifiable factors (Vitamin D level, activity level, hormone status, etc.), and whether BMD and BMC is recovered beyond 1 year.

Understanding intestinal glucose transporter expression in obese compared to non-obese subjects.

INTRODUCTION: The impact of Roux-en-Y gastric bypass (RYGB) on weight loss and co-morbid disease resolution is well established. However, the mechanisms underlying the procedure remain incompletely understood. Intestinal remodeling involving glucose transporters (GLUTs) may play a crucial role. Rat studies have demonstrated morphological adaptation of GLUTs within adipose and intestinal cells in association with the reprogramming of glucose metabolism. There is a limited understanding of the variations in expression amongst GLUT family receptors in the human intestine. The aim of this study was to evaluate and describe jejunal GLUT expression patterns in the obese versus non-obese. METHODS: Tissue samples were collected from 19 adults (age ≥18) patients with morbid obesity undergoing elective RYGB. Specimens were obtained from excess jejunum removed during the stapled jejuno-jejunal anastomosis. All subjects met National Institutes of Health criteria for bariatric surgery (body mass index or BMI ≥40 or ≥35 with obesity-related comorbidities). Exclusion criteria included age less than 18, age greater than 65, patients undergoing a revision procedure, and the presence of a seizure disorder (possible association with GLUT-1 deficiency syndrome). Five samples were obtained from non-obese subjects (average BMI 26.7) without diabetes who were consenting organ donors after brain death. Samples of jejunum from non-obese individuals were obtained at the time of organ procurement. Institutional Review Board and Gift of Hope approval was obtained. Specimens underwent quantitative real-time PCR and Western blotting. Western blot densitometry was performed using Image J software. Student T test was performed using SPSS statistics software. RESULTS: GLUT-1 and GLUT-7 expression were not detected in the jejunum of either group. No difference in expression pattern was observed for GLUT-2, GLUT-4, and GLUT-9 between the groups. Western blot band density of GLUT-5 to loading control (GADPH) mean ratio was 0.21 (SD = 0.20) in obese specimens compared to 0.56 (SD = 0.17) in non-obese. Densitometry revealed GLUT-5 levels in the jejunum of the obese were significantly lower than non-obese specimens (P < 0.05). CONCLUSION: The absence of GLUT-1 expression in both the obese and non-obese groups is consistent with the established view of GLUT-1 being abundantly present in fetal intestine but diminished to negligible levels by adulthood. Decreased GLUT-5 expression in samples from subjects with obesity compared to non-obese samples may represent a down-regulation of gene expression amongst the obese. The differential expression of GLUT-5 suggests a possible role in obesity. Studies of GLUT family expression will aid in understanding the impact of intestinal remodeling on obesity.

Gastric Bypass Surgery Leads to Long-term Remission or Improvement of Type 2 Diabetes and Significant Decrease of Microvascular and Macrovascular Complications.

OBJECTIVES: The aim of the study was to compare long-term outcomes of 2 groups of morbidly obese patients with type 2 diabetes mellitus-1 managed by Roux-en-Y gastric bypass surgery and a comparable group managed medically. METHODS: The present study was a single-institution retrospective study. Of the 173 obese patients with type 2 diabetes mellitus undergoing gastric bypass surgery between January 2000 and July 2004, 78 patients (45%) were followed for at least 10 years. The control group consisted of 80 diabetic obese patients from the same period with similar body mass index, age, race, and severity of diabetes. The median follow-up was 11 years for both the groups. RESULTS: The group undergoing gastric bypass surgery had greater percentage of excess weight loss than the control group-66% versus -1.6%, respectively. Forty-one patients (52.6%) in the surgery group had complete remission of diabetes and 5 (6.4%) had partial remission. Twelve patients (15.4%) had diabetes recurrence after initial remission. No patient in the control group had remission of diabetes. Compared with the control group, the group undergoing gastric bypass surgery had a significantly reduced incidence of microvascular complications-46.3% versus 11.5%, and macrovascular complications-20.3% versus 5%, respectively (P < 0.01). CONCLUSIONS: In this study, we demonstrated that after 10 years of follow-up, Roux-en-Y gastric bypass surgery, compared with nonsurgical medical management, resulted in significantly greater weight loss, reduction in hemoglobin A1c, and use of antidiabetic medications, and very importantly a lower incidence of both microvascular and macrovascular complications in obese patients with type 2 diabetes.

Post-gastric bypass hypoglycaemia: a review.

Bariatric surgery is a highly effective treatment for severe obesity, resulting in substantial weight loss and normalizing obesity-related comorbidities. However, long-term consequences can occur, such as postbariatric surgery hypoglycaemia. This is a challenging medical problem, and the number of patients presenting with it has been increasing. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it is the surgery most commonly associated with the development of postbariatric surgery hypoglycaemia. To date, the pathogenesis of this condition has not been completely established. However, various factors - particularly increased postprandial glucagon-like peptide (GLP)-1 secretion - have been considered as crucial mediator. The mechanisms responsible for diabetic remission after bariatric surgery may be responsible for the development of hypoglycaemia, which typically occurs 1-3 h after a meal and is concurrent with inappropriate hyperinsulinaemia. Carbohydrate-rich foods usually provoke hypoglycaemic symptoms, which can typically be alleviated by strict dietary modifications, including carbohydrate restriction and avoidance of high glycaemic index foods and simple sugars. Few patients require further medical intervention, such as medications, but some patients have required a pancreatectomy. Because this option is not always successful, it is no longer routinely recommended. Clinical trials are needed to further determine the pathophysiology of this condition as well as the best diagnostic and treatment approaches for these patients.

Gastric bypass significantly improves quality of life in morbidly obese patients with type 2 diabetes.

OBJECTIVE: To evaluate the impact of Roux-en-Y gastric bypass (RYGB) on quality of life in obese diabetic patients compared to standard medical therapy for type 2 diabetes mellitus. METHODS: We prospectively studied two matched obese populations with type 2 diabetes. Thirty patients underwent laparoscopic RYGB and 31 received standard medical therapy combined with a diabetes support and education program (DSE), consisting of educational sessions on diet and exercise. Groups were matched by age, gender, weight, glucostatic parameters, and use of glucose-lowering medications (oral agents and insulin therapy). Health-related quality of life (HRQOL) was assessed using the normalized SF-36 questionnaire, and data were collected at baseline and at 12-month follow-up. RESULTS: Diabetic patients who underwent RYGB experienced a statistically significant increase in their overall HRQOL. However, the role-physical and mental health domains increased but did not reach statistical significance. Diabetic patients in the medical therapy and DSE group did not show any significant increase in HRQOL. The between-group differences for the HRQOL changes from baseline were significant, other than for role-physical and mental health domains. Percentage changes in glucostatic parameters, discontinuation of glucose-lowering medications, and T2DM remission were not found to predict the percentage change in SF-36 scores at 12 months after RYGB. CONCLUSIONS: For the first time, with a prospective matched control study, we demonstrate a significant improvement in HRQOL in obese diabetic patients who underwent RYGB, but not in those who were offered standard medical therapy and DSE.

Effects of Roux-en-Y gastric bypass or diabetes support and education on insulin sensitivity and insulin secretion in morbidly obese patients with type 2 diabetes.

OBJECTIVE: The long-term changes in insulin sensitivity and ß-cell function in morbidly obese patients with type 2 diabetes mellitus who undergo Roux-en-Y gastric bypass (RYGB) surgery or standard medical care remain unclear. We prospectively studied longitudinal changes of glucostatic parameters in morbidly obese patients with type 2 diabetes mellitus undergoing RYGB surgery or diabetes support and education (DSE). RESEARCH METHODS AND DESIGN: Sixty-one morbidly obese subjects (41.7 ± 0.6 kg/m) with type 2 diabetes mellitus were assigned to RYGB surgery (n = 30) or DSE (n = 31). They were matched for sex, age, and body weight. Insulin sensitivity index (Si) and acute insulin response (AIR) were derived from frequently sampled intravenous glucose tolerance test. Body composition was measured using dual-energy x-ray absorptiometry. General linear model with repeated measures was used to examine the longitudinal changes (baseline, 6 months, 12 months) in these parameters. RESULTS: At 12-month follow-up, significant improvement in obesity measures, body composition, glucose homeostasis, Si, and AIR was observed after RYGB surgery and weight loss. These outcomes were not influenced by preoperative insulin use. Although there were no significant changes in the body composition among DSE subjects, they experienced a decline in the Si and AIR, along with an increase in fasting glucose and HbA1c. The between-group differences in Si and AIR at 12-month follow-up were completely attenuated with adjustment to changes in body weight. CONCLUSIONS: The long-term effects of RYGB surgery on glucostatic parameters are partly dependent on weight loss. In morbidly obese patients with diabetes who were offered DSE, a progressive decline in the glucose homeostasis and glucostatic parameters is observed despite absence of weight gain. (NCT00787670).

Postprandial metabolite profiles reveal differential nutrient handling after bariatric surgery compared with matched caloric restriction.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery results in exaggerated postprandial insulin and incretin responses and increased susceptibility to hypoglycemia. OBJECTIVE: We examined whether these features are due to caloric restriction (CR) or altered nutrient handling. METHODS: We performed comprehensive analysis of postprandial metabolite responses during a 2-hour mixed-meal tolerance (MMT) test in 20 morbidly obese subjects with type 2 diabetes who underwent RYGB surgery or matched CR. Acylcarnitines and amino acids (AAs) were measured using targeted mass spectrometry. A linear mixed model was used to determine the main effect of interventions and interaction term to assess the effect of interventions on postprandial kinetics. RESULTS: Two weeks after these interventions, several gut hormones (insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide 1), glucose, and multiple AAs, including branched-chain and aromatic species, exhibited a more rapid rate of appearance and clearance in RYGB surgery subjects than in CR subjects during the MMT test. In the RYGB surgery group, changes in leucine/isoleucine, methionine, phenylalanine, and glucagon-like peptide 1 response were associated with changes in insulin response. Levels of alanine, pyruvate, and lactate decreased significantly at the later stages of meal challenge in RYGB surgery subjects but increased with CR. CONCLUSIONS: RYGB surgery results in improved metabolic flexibility (ie, greater disposal of glucose and AAs and more complete ß-oxidation of fatty acids) compared with CR. The changes in the AA kinetics may augment the hormonal responses seen after RYGB surgery. The reduction in key gluconeogenic substrates in the postprandial state may contribute to increased susceptibility to hypoglycemic symptoms in RYGB surgery subjects.

Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis.

Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleotide polymorphisms (SNPs) across genes of choline/1-carbon metabolism and functionally related pathways increase susceptibility to developing hepatic steatosis. In biopsy-characterized cases of nonalcoholic fatty liver disease and controls, we assessed 260 SNPs across 21 genes in choline/1-carbon metabolism. When SNPs were examined individually, using logistic regression, we only identified a single SNP (PNPLA3 rs738409) that was significantly associated with severity of hepatic steatosis after adjusting for confounders and multiple comparisons (P=0.02). However, when groupings of SNPs in similar metabolic pathways were defined using unsupervised hierarchical clustering, we identified groups of subjects with shared SNP signatures that were significantly correlated with steatosis burden (P=0.0002). The lowest and highest steatosis clusters could also be differentiated by ethnicity. However, unique SNP patterns defined steatosis burden irrespective of ethnicity. Our results suggest that analysis of SNP patterns in genes of choline/1-carbon metabolism may be useful for prediction of severity of steatosis in specific subsets of people, and the metabolic inefficiencies caused by these SNPs should be examined further.

Cardiovascular risk in obese diabetic patients is significantly reduced one year after gastric bypass compared to one year of diabetes support and education.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) reduces most of the obesity-related comorbidities known to increase the cardiovascular risk in obese subjects. The Framingham risk score (FRS) is designed to be independent of body weight and estimates the 10-year risk for coronary heart disease (CHD), myocardial infarction, stroke, cardiovascular disease (CVD), death from CHD, and death from CVD. Our aim was to evaluate the effectiveness of RYGB on improving the FRS when compared to a matched control group who underwent diabetes support and education program (DSE). METHODS: In a prospective cohort study, we evaluated preoperatively and at 12 months, 61 morbidly obese subjects with diabetes. Thirty underwent laparoscopic RYGB, and 31 received 1 year of DSE, consisting of educational sessions on diet, nutrition, and exercise. Groups were matched for gender, age, weight, blood pressure, and cholesterol and triglyceride levels. Strict gender-specific FRS was used to assess the cardiovascular risk. RESULTS: Excess weight-loss percentages (%EWL) were 55.6 ± 15.1 in the RYGB group and 1.2 ± 10.8 in the DSE group (P < 0.001). The two groups were matched for baseline FRS. RYGB patients experienced a significant decrease in all FRS, whereas control subjects did not show a significant decrease for the 10-year risk for CHD, CVD and death from CVD. The between-group differences for changes from baseline to 12 months in all FRS were significant. The 10-year risk reductions for CHD, MI, stroke, CVD, death from CHD, and death from CVD in the RYGB group relative to the DSE group were, respectively, 42, 48, 30, 39, 50, and 50%. No correlations between reduction in FRS and %EWL were found after RYGB. CONCLUSIONS: A significant improvement in the 10 year estimated cardiovascular risk is observed in patients undergoing RYGB, but not in those who were offered usual medical therapy plus DSE. However, the effects of RYGB on FRS are independent of weight loss.

Improved insulin sensitivity after gastric bypass correlates with decreased total body fat, but not with changes in free fatty acids.

BACKGROUND: Increased plasma free fatty acids (FFAs) are considered one of the key elements in the pathogenesis of insulin resistance (IR) and type 2 diabetes (T2DM). We hypothesize that, in diabetic patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB), a postoperative decrease in FFA will correlate with improved insulin sensitivity (Si). METHODS: A total of 30 obese [body mass index ((BMI) >35 kg/m(2)] patients with a diagnosis of T2DM were studied preoperatively and 12 months after LRYGB in a prospective cohort study. Collected data included intravenous glucose tolerance test (IVGTT), total body composition by dual-energy X-ray absorptiometry and plasma levels of FFA. Si analysis from the IVGTT was estimated from minimal model analysis. Pre- and postoperative variables were compared using a paired sample t test. Relationships between changes in variables were determined with Pearson's correlation test. RESULTS: Twelve months after LRYGB the study population showed a significant decrease in BMI (p = 0.001), FFA (p = 0.03), and total body fat (p = 0.03), with an increase in Si (p = 0.001). Postoperative changes in Si significantly correlated (Pearson's r = -0.53, p = 0.01) with change in total body fat, but not with changes in plasma FFA (Pearson's r = -0.22, p = 0.31). CONCLUSIONS: Our study challenges the notion that IR is mediated to a significant degree by changes in plasma FFA concentration. Instead, changes in adiposity and consequently changes in adipokine release can be the key players in determining remission of T2DM after LRYGB.

Esophageal acid-clearance physiology is altered after Nissen-Collis gastroplasty.

BACKGROUND: Nissen-Collis gastroplasty (NCG) is an effective treatment for short esophagus, but it sometimes is associated with abnormal postoperative esophageal acid exposure. This study was designed to test the hypothesis that NCG prevents gastric reflux and that pathologic distal esophagus acid exposure is due to prolonged acid clearance in the "neoesophagus." METHODS: The study enrolled 11 normal healthy subjects (ten patients status post--laparoscopic Nissen fundoplication and nine patients status post-NCG). All the participants were age and gender matched, and all were studied via manometry, acid-clearance test, and 24-h pH analysis. The clearance test was performed according to an established protocol. A 15-ml acid bolus (pH 1.2) was rapidly infused (×4) using a nasogastric tube 15 cm proximal to the lower esophageal sphincter, followed by dry swallows every 30 s until the esophageal pH rose above 4. RESULTS: All the subjects had normal esophageal peristalsis and distal amplitudes. The acid-clearance time was significantly higher with NCG (P < 0.001 vs Nissen and normal subjects). Pathologic esophageal acid exposure occurred in one of ten Nissen patients (10 %) and in two of nine NCG patients (22 %) (nonsignificant difference [NS]). The median distal esophageal acid exposure time during the 24-h pH study was similar in the two groups (NCG, 1.2 %; Nissen, 2.5 %; NS). CONCLUSIONS: The findings showed that NCG is an adequate antireflux procedure but that it is characterized by a delayed esophageal acid clearance.

Case-matched analysis comparing outcomes of revisional versus primary laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most common approaches used to revise post-bariatric patients with inadequate weight loss or significant weight regain. Previous studies have analyzed the outcomes of open revisional RYGB versus primary RYGB, but no case-control matched analysis comparing revisional LRYGB versus primary LRYGB has been performed. METHODS: Our cohort includes 37 consecutive patients who underwent revisional LRYGB because of unsatisfactory weight loss or weight regain matched in a 1:2 ratio with 74 control patients who underwent primary LRYGB. Matching included the following parameters: age, gender, preoperative body mass index and comorbidities (diabetes, obstructive sleep apnea, and hypertension). RESULTS: The revisional group had longer length of stay compared with the primary group (3.8 vs. 2.4 days, P = 0.02) and a higher conversion to laparotomy rate (10.8 vs. 0 %, P = 0.01). The revisional group had a higher 30-day morbidity compared with the primary group (27 vs. 8.1 %, P = 0.02). There were no deaths in both groups. The two groups had similar 30-day readmission and 30 day reoperation rates. At 3, 6, and 12 months of follow-up, the revisional LRYGB group had significantly lower percent of excess weight loss (EWL) than the primary LRYGB group (3 months, 30 vs. 38.4, P = 0.001; 6 months, 36.3 vs. 52.9, P = 0.001; 12 months, 46.5 vs. 68.2, P = 0.001). CONCLUSIONS: Revisional LRYGB is characterized by lower EWL and higher morbidity than primary LRYGB. However, our data suggest that revisional LRYGB is still capable of providing significant weight loss in these high-risk patients.

Ursodiol Prescriptions Following Bariatric Surgery: National Prescribing Trends and Outcomes.

BACKGROUND: Rapid weight loss after bariatric surgery is a risk factor for gallstone development. Numerous studies have shown that ursodiol after surgery decreases rates of gallstone formation and cholecystitis. Real-world prescribing practices are unknown. This study aimed to examine prescription patterns for ursodiol and reassess its impact on gallstone disease using a large administrative database. METHODS: The Mariner database (PearlDiver, Inc.) was queried using Current Procedural Terminology codes for Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between 2011 and 2020. Only patients with International Classification of Disease codes for obesity were included. Patients with pre-operative gallstone disease were excluded. The primary outcome was gallstone disease within 1 year, which was compared between patients who did and did not receive an ursodiol prescription. Prescription patterns were also analyzed. RESULTS: Three hundred sixty-five thousand five hundred patients fulfilled inclusion criteria. Twenty-eight thousand seventy-five (7.7%) patients were prescribed ursodiol. There was a statistically significant difference in development of gallstones (p < 0.001), development of cholecystitis (p = .049), and undergoing cholecystectomy (p < 0.001). There was a statistically significant decrease in the adjusted odds ratio (aOR) for the development of gallstones (aOR 0.81, 95% CI: 0.74, 0.89), development of cholecystitis (aOR 0.59, 95% CI: 0.36, 0.91), and undergoing cholecystectomy (aOR 0.75, 95% CI: 0.69, 0.81). CONCLUSION: Ursodiol significantly decreases the odds of development of gallstones, cholecystitis, or cholecystectomy within 1 year following bariatric surgery. These trends hold true when analyzing RYGB and SG separately. Despite the benefit of ursodiol, only 10% of patients received an ursodiol prescription postoperatively in 2020.

Serum leptin levels are inversely correlated with omental gene expression of adiponectin and markedly decreased after gastric bypass surgery.

BACKGROUND: Adipose tissue is the most abundant endocrine tissue in the body, producing leptin, a hormone important in regulating hunger, and adiponectin, a hormone involved in insulin sensitivity and inflammation. This study aimed to assess the impact of gastric bypass surgery (GBS) on leptin levels and its relation to the adipose tissue expression of adiponectin. METHODS: Omental and subcutaneous adipose tissue and serum were obtained from 40 obese patients undergoing GBS, from 13 patients 1 year or more after GBS, and from 16 non-obese individuals with a body mass index of 20 to 29 kg/m(2). Adiponectin gene expression was measured by quantitative real-time polymerase chain reaction, and the gene expression was normalized for the GAPDH gene. Serum leptin and adiponectin were measured by a high-sensitivity enzymatic assay. RESULTS: Leptin levels were significantly lower in the post-GBS patients (19.8 ± 6.7) than in the pre-GBS patients (59.0 ± 5.1; P = 0.0001), and similar to those in the non-obese control subjects (18.2 ± 4; P = 0.8). Univariate analysis showed an inverse correlation between serum leptin levels and omental adiponectin gene expression (r = -0.32; P = 0.01). CONCLUSIONS: Gastric bypass surgery results in resolution of the leptin resistance status that characterizes obese subjects. The study also demonstrated a significant correlation between leptin and adiponectin. This correlation provides preliminary evidence for studying a potential adiponectin-leptin cross-talking that may represent one of the physiologic pathways responsible for the regulation of food intake in humans.

Adipogenic differentiation of adipose tissue-derived human mesenchymal stem cells: effect of gastric bypass surgery.

BACKGROUND: Adipose tissue dysfunction is an important feature of obesity characterized by enlarged adipocytes and marked changes in secretion of cytokines. These changes result in insulin resistance, chronic vascular inflammation, oxidative stress, and activation of the renin-angiotensin system (RAS), eventually leading to type 2 diabetes, obesity-related hypertension, and cardiovascular disease (CVD). Several trials have shown that bariatric surgery significantly reduces these comorbidities. However, there is a gap in knowledge regarding the mechanisms whereby bariatric surgery reduces the burden of CVD in obese individuals. METHOD: Mesenchymal stem cells (MSCs) were isolated from adipose tissue collected from three groups: (1) nonobese control subjects, (2) obese subjects undergoing gastric bypass surgery (GBS), and (3) subjects 1 year or more after GBS. In the study, MSCs were induced to adipogenic differentiation, and RAS-related gene expressions were determined by quantitative polymerase chain reaction. The effect of angiotensin II (Ang II) on adipogenic differentiation of MSCs also was investigated. RESULTS: Angiotensinogen mRNA levels in MSCs and differentiated adipocytes were significantly higher in the obese group than in the nonobese control subjects. Renin mRNA levels were significantly higher in the obese group MSCs than in the nonobese and post-GBS groups. Angiotensin-converting enzyme mRNA levels were significantly lower in the MSCs derived from the post-GBS group than in the obese and nonobese control subjects. Serum Ang II levels were significantly lower in the post-GBS group (52.1 ± 4.2 pg/ml) than in the nonobese (85.4 ± 12.4 pg/ml) and obese (84.7 ± 10.0 pg/ml) groups. Ang II treatment inhibited adipogenesis of MSCs in a dose-dependent manner. The inhibitory effect of Ang II was mainly abolished by PD123319, a receptor 2 blocker. CONCLUSIONS: The adipogenesis of MSCs is inhibited by Ang II treatment. Obese individuals are characterized by an upregulation of the RAS-related gene expressions in adipose tissue. This upregulation resolves in post-GBS subjects.

Gastric bypass surgery restores meal stimulation of the anorexigenic gut hormones glucagon-like peptide-1 and peptide YY independently of caloric restriction.

BACKGROUND: The effects of gastric bypass surgery on the secretion of the anorexigenic gut-derived hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), independent of caloric restriction and due to different dietary macronutrients, is not well characterized. This study examines the effects of a mixed-nutrient or high-fat liquid meal on the postprandial stimulation of GLP-1 and PYY following gastric bypass or equivalent hypocaloric diet. METHODS: Total PYY and active GLP-1 were measured fasting and at multiple points after standardized mixed-nutrient and high-fat liquid meals in two matched groups of obese subjects. The meal stimulation tests were performed before and 14.6 ± 3.3 days after gastric bypass (GBP, n = 10) and before and after a 7-day hypocaloric liquid diet matching the post-GBP diet (control, n = 10). RESULTS: Mixed-nutrient and high-fat postprandial GLP-1 levels increased following GBP (mixed-nutrient peak: 85.0 ± 28.6-323 ± 51 pg/ml, P < 0.01; high-fat peak: 81.8 ± 9.6-278 ± 49 pg/ml, P < 0.01), but not after diet (mixed-nutrient peak: 104.4 ± 9.4-114.9 ± 15.8 pg/ml, P = NS; high-fat peak: 118.1 ± 16.4-104.4 ± 10.8 pg/ml, P = NS). The postprandial PYY response also increased after GBP but not diet, though the increase in peak PYY did not reach statistical significance (GBP mixed-nutrient peak: 134.8 ± 26.0-220.7 ± 52.9 pg/ml, P = 0.09; GBP high-fat peak: 142.1 ± 34.6-197.9 ± 12.7 pg/ml, P = 0.07; diet mixed-nutrient peak: 99.8 ± 8.0-101.1 ± 13.3 pg/ml, P = NS; diet high-fat peak: 105.0 ± 8.8-103.1 ± 11.8 pg/ml, P = NS). The postprandial GLP-1 response was not affected by the macronutrient content of the meal. However, following GBP the mixed-nutrient PYY total area under the curve (AUC(0-120)) was significantly greater than the high-fat PYY AUC(0-120) (22,081 ± 5,662 pg/ml min vs. 18,711 ± 1,811 pg/ml min, P = 0.04). CONCLUSIONS: Following GBP there is an increase in the postprandial stimulation of PYY and GLP-1 that is independent of caloric restriction. The phenomenon of "bariatric surgery-induced anorexia" may be linked to the increased levels after GBP.

Two Cases of Heterotopic Pancreas of the Small Bowel Incidentally Found During Laparoscopic Bariatric Surgery.

Background: We present two cases of incidentally found heterotopic pancreas during laparoscopic bariatric surgery. Heterotopic pancreas is a rare congenital anomaly where pancreatic tissue is located outside of the pancreas. These lesions may be encountered incidentally during surgery, which raise unexpected management questions. Case 1: A single pathology confirmed ectopic pancreas lesion encountered in the jejunem during laparoscopic Roux-en Y gastric bypass. Case 2: Two pathology confirmed heterotopic pancreas lesions encountered in the jejunem during laparoscopic Roux-en Y gastric bypass. Discussion: Heterotopic pancreas lesions are generally benign and encountered incidentally during intra-abdominal surgery. Surgeons must decide whether to resect the incidentally found mass. When encountered intraoperatively, a heterotopic pancreas lesion found in the small bowel without concerning features should be considered benign and does not warrant resection or biopsy.

Changes of Circulating Irisin and High-Sensitivity C-Reactive Protein Levels in Morbidly Obese Individuals with Type 2 Diabetes After Roux-en-Y Gastric Bypass.

Background: Irisin has been recently reported to provide beneficial effects in obesity and diabetes. Elevation of high-sensitivity C-reactive protein (hs-CRP) reflects the inflammatory state that has been shown to play a key role in obesity and its comorbidities. Objective: Our study aimed to compare the changes of circulating irisin levels in an obese diabetic population who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) versus a control-matched population who underwent usual medical care plus diabetes support education (DSE) program. In addition, we aimed to explore the association between circulating irisin and hs-CRP levels after the interventions. Methods: In a prospective controlled trial, we studied 58 obese individuals with type 2 diabetes before and 12 months after intervention. Twenty-nine subjects underwent LRYGB and 29 subjects received DSE. Results: At 12-month follow-up, compared with the DSE group, patients who underwent LRYGB lost more weight (LRYGB; -33.4 ± 11.2, and DSE; 0.2 ± 4.9 kg; P < .001), fat mass (P < .001), and fat-free mass (P < .05). Circulating irisin (P < .05) and hs-CRP level (P < .05) were also significantly lower. Within the LRYGB group, the reduction of irisin level was positively associated with the changes of hs-CRP levels (r = 0.39, P < .05). Conclusions: To the best of our knowledge, this is the first study showing that LRYGB significantly reduces circulating irisin levels compared with usual medical care and DSE, in an obese diabetic population. After LRYGB, the irisin reduction significantly correlates with the reduction of hs-CRP. The elevation of circulating irisin levels suggests irisin resistance in the obese state and its decrease after LRYGB might reflect the resolution of irisin resistance. Future investigations are needed to confirm and explore the mechanisms of irisin resistance in obesity, its resolution after LRYGB, and the pathophysiological significance.

Social determinants of health and their impact on rates of postoperative complications among patients undergoing vertical sleeve gastrectomy.

BACKGROUND: Vertical sleeve gastrectomy is one of the most common bariatric procedures worldwide, but the impact of social determinants of health on postoperative outcomes for this procedure has not been well characterized. The objective of this study was to analyze the impact that social determinants of health have on postoperative outcomes after vertical sleeve gastrectomy. METHOD: This was a population-based study using the MARINER-15 database, an all-payer claims database. The primary endpoint of this study was the development of any complication, including cardiac complication, acute kidney injury, deep vein thrombosis, wound complication, hematoma, pneumonia, pulmonary embolism, transfusion, or urinary tract infection within 60 days, 30- and 90-day all-cause mortality, or readmission within 30 or 90 days in patients undergoing vertical sleeve gastrectomy procedures. RESULTS: Individuals in the social determinants of health cohort had a significantly longer length of stay when compared with those without social determinants of health (3.07 days vs 1.582 days, P < .001). These patients were more likely to develop any complication within 60 days after surgery (hazard ratio 1.20, 95% confidence interval 1.03-1.40) but were less likely to return for readmission within 30 and 90 days (hazard ratio 0.80, 95% confidence interval 0.66-0.96; hazard ratio 0.85 95% confidence interval 0.72-0.99). CONCLUSION: Vertical sleeve gastrectomy is an effective treatment for morbid obesity and its associated comorbidities. Although patients with social determinants of health are more likely to develop any of the analyzed postoperative complications within 60 days, they are less likely to return for readmission, highlighting the importance of focused follow-up and other measures to avoid lapses in care and eliminate further barriers to care in this population.