Roux-en-Y Gastric Bypass Surgery Research Articles

PBPK Modeling of Azithromycin Systemic Exposure in a Roux-en-Y Gastric Bypass Surgery Patient Population.

In this investigation, PBPK modeling using the Simcyp® Simulator was performed to evaluate whether Roux-en-Y gastric bypass (RYGB) surgery impacts the oral absorption and bioavailability of azithromycin. An RYGB surgery patient population was adapted from the published literature and verified using the same probe medications, atorvastatin and midazolam. Next, a PBPK model of azithromycin was constructed to simulate changes in systemic drug exposure after the administration of different oral formulations (tablet, suspension) to patients pre- and post-RYGB surgery using the developed and verified population model. Clinically observed changes in azithromycin systemic exposure post-surgery following oral administration (single-dose tablet formulation) were captured using PBPK modeling based on the comparison of model-predicted exposure metrics (Cmax, AUC) to published clinical data. Model simulations predicted a 30% reduction in steady-state AUC after surgery for three- and five-day multiple dose regimens of an azithromycin tablet formulation. The relative bioavailability of a suspension formulation was 1.5-fold higher than the tablet formulation after multiple dosing. The changes in systemic exposure observed after surgery were used to evaluate the clinical efficacy of azithromycin against two of the most common pathogens causing community acquired pneumonia based on the corresponding AUC24/MIC pharmacodynamic endpoint. The results suggest lower bioavailability of the tablet formulation post-surgery may impact clinical efficacy. Overall, the research demonstrates the potential of a PBPK modeling approach as a framework to optimize oral drug therapy in patients post-RYGB surgery.

OR13-04 Risk Of Wrist Fracture In Gastric Bypass Compared To Gastric Banding As Estimated By The Load-To-Strength Ratio

Abstract Disclosure: G.H. Jung: None. B. Zahedi: None. K. Lindeman: None. C.C. Rushin: None. M.C. Cheney: None. M.L. Bouxsein: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Background: Bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) lead to long-term deficits in bone density but are also accompanied by decreased weight, which may lower the impact force with falls. Given that risk of fracture is dependent on both bone strength and the external force applied to bone, the clinical implications of these opposing effects are unclear. The aim of this study is to compare the long-term skeletal impact of RYGB and AGB using a biomechanical evaluation of load-to-strength ratio as a surrogate for fracture risk. Methods: We examined a cohort of adults who received RYGB and AGB surgery ≥ 10 years ago (RYGB: n=25; AGB: n=25). We computed the load-to-strength ratio at the distal radius as a ratio of impact force to bone strength, with higher load-to-strength ratios representing a higher susceptibility to fracture. Impact force (F) was calculated for a forward fall via a single-spring biomechanical model. High-resolution peripheral quantitative CT was used to estimate bone strength via microfinite element analysis. Participants also had dual-energy X-ray absorptiometry measurements of areal bone mineral density (aBMD) at the spine, hip, and distal radius, along with laboratory evaluations (parathyroid hormone, PTH; C-telopeptide, CTX; type 1 procollagen, P1NP; 25OH-vitamin D). Differences in bone outcomes between RYGB and AGB groups were compared using generalized linear modeling in R version 4.2.2 and adjusted for age, sex/menopausal status, and race/ethnicity. Results: The RYGB and AGB groups were each comprised of 22 women and 3 men. Compared to AGB, the RYGB group was younger (56 vs 62 years), had more premenopausal women (41% vs 9%), more individuals who identified as Black (36% vs 8%) and longer duration since surgery (13 vs 11 years) (p<0.05 for all). Current BMI (34.5 kg/m^2) was similar between groups, although postsurgical weight loss was higher in RYGB (45 vs. 27 kg, p<0.001). In multivariate analysis, in comparison to AGB, the RYGB group had 98% higher CTX and 34% higher P1NP levels (P<0.01 for both), as well as 20% lower total vBMD at the distal radius, 12% lower total hip, 10% lower femoral neck and 8% lower spinal aBMD (P<0.05 for all). Although impact forces were similar in the 2 groups, RYGB had a 12% lower estimated bone strength (3768 ± 182 vs. 4236 ± 193 N, p=0.01). Load-to-strength ratio was numerically higher in RYGB as compared with AGB (0.78 ± 0.05 vs 0.69± 0.06, p=0.1), suggestive of higher fracture risk, although this did not reach statistical significance. Conclusions: Despite achieving similar postoperative weight as AGB, RYGB patients had lower estimated bone strength at the distal radius, higher bone turnover markers, lower BMD and a trend for higher load-to-strength ratio ≥10 years after surgery. Taken together, these results indicate the long-term deleterious skeletal effects are more concerning with RYGB than AGB. Presentation: Friday, June 16, 2023

Post-bariatric hypoglycaemia diagnosed during pregnancy.

There is a scarcity of literature relating to post-bariatric hypoglycaemia (PBH) in pregnancy. Recurrent hyperglycaemia and hypoglycaemia can have significant consequences for both the mother and the developing fetus. We describe a case of a young pregnant woman who was diagnosed with symptomatic PBH in the second trimester of pregnancy using continuous glucose monitoring (CGM) 3 years after Roux-en-Y gastric bypass (RYGB) surgery. Instigating a low glycaemic index and complex carbohydrate diet significantly improved the patient's glycaemic excursions. Given that this condition is likely underdiagnosed as a complication of RYGB surgery, a greater awareness of this complication is needed. Patients should be adequately consented pre-operatively for this relatively frequent late surgical complication to enable patients to identify symptoms of this condition at an early stage and seek medical treatment. PBH is an important diagnosis in patients post-RYGB surgery, particularly in women of childbearing age when consequences of both hyperglycaemia and hypoglycaemia during pregnancy can adversely affect both mother and the fetus. Adverse outcomes of recurrent hypoglycaemia to the fetus can include small for gestational age, intrauterine growth restriction and possible impairment of beta cell function. Providing adequate carbohydrate intake to allow growth of the fetus during pregnancy while also attempting to resolve both hyperglycaemia and hypoglycaemia associated with PBH by reducing the intake of simple carbohydrates and high glycaemic index foods can prove challenging. Patients should be adequately consented for late complications of RYGB surgery such as PBH in order to allow early recognition of symptoms and enable prompt treatment.

The Impact of COVID-19 Pandemic on Weight Loss, Eating Behaviour and Quality of Life after Roux-en-Y Gastric Bypass.

Background and Objectives: The global pandemic of coronavirus disease (COVID-19), declared on 11 March 2020, had an extensive impact on bariatric patients. The aim of this study was to evaluate short-term weight loss outcomes, changes in eating behaviour, and health-related quality of life (HRQoL) among patients who had Roux-en-Y gastric bypass (RYGB) before and during the COVID-19 pandemic. Materials and Methods: This cohort study included 72 patients (Group S) who underwent RYGB surgery in the Surgery Department of the Lithuanian University of Health Sciences during the COVID-19 pandemic in the years 2020-2022. Data for the control group (Group C) of 87 patients (operated on in 2010-2012) were collected from a prospective study. The data referred to the period before and a year after the RYGB. The information about patients' weight changes, hunger, satiety, fullness sensations, appetite, diet, and eating patterns was queried. Eating behaviour and HRQoL evaluation were conducted by the Three-Factor Eating Questionnaire (TFEQ-R18) and the medical outcomes study Short-Form-36 (SF-36), respectively. Results: One year after the surgery, % excess body mass index loss (%EBMIL) was 77.88 (26.33) in Group S, 76.21 (19.98) in Group C, p = 0.663. Patients in Group S tended more to choose snacks between main meals: 79.2% versus 28.7%, p < 0.0001. Cognitive restraint significantly increased in Group S from 45.93 (13.37) up to 54.48 (13.76), p = 0.001; additionally, significantly worse overall health status was found in Group S compared to Group C, 53.27 (24.61) versus 70.11 (31.63), p < 0.0001. Mental HRQoL (50.76 versus 60.52 score, p < 0.0001) and social functioning (44.79 versus 57.90, p < 0.0001) were worse in Group S. Conclusions: In this study, the COVID-19 pandemic had no impact on short-term weight loss after RYGB. However, one year after, RYGB patients tended to snack more, and mental HRQoL and social functioning were worse in the study group.

Binge Eating (BE) and Obesity: Brain Activity and Psychological Measures before and after Roux-En-Y Gastric Bypass (RYGB).

Brain activity in response to food cues following Roux-En-Y Gastric Bypass (RYGB) in binge eating (BE) or non-binge eating (NB) individuals is understudied. Here, 15 RYGB (8 BE; 7 NB) and 13 no treatment (NT) (7 BE; 6 NB) women with obesity underwent fMRI imaging while viewing high and low energy density food (HEF and LEF, respectively) and non-food (NF) visual cues. A region of interest (ROI) analysis compared BE participants to NB participants in those undergoing RYGB surgery pre-surgery and 4 months post. Results were corrected for multiple comparisons using liberal (p < 0.006 uncorrected) and stringent (p < 0.05 FDR corrected) thresholds. Four months following RYGB (vs. no treatment (NT) control), both BE and NB participants showed greater reductions in blood oxygen level-dependent (BOLD) signals (a proxy of local brain activity) in the dorsomedial prefrontal cortex in response to HEF (vs. LEF) cues (p < 0.006). BE (vs. NB) participants showed greater increases in the precuneus (p < 0.006) and thalamic regions (p < 0.05 corrected) to food (vs. NF). For RYGB (vs. NT) participants, BE participants, but not NB participants, showed lower BOLD signal in the middle occipital gyrus (p < 0.006), whilst NB participants, but not BE participants, showed lower signal in inferior frontal gyrus (p < 0.006) in response to HEF (vs. LEF). Results suggest distinct neural mechanisms of RGYB in BE and may help lead to improved clinical treatments.

New Mouse Models of Roux-en Y Gastric Bypass and One Anastomosis Gastric Bypass for Type 2 Diabetes.

Current bariatric surgery models primarily utilize mice with obesity, overlooking those with type 2 diabetes (T2DM). These models have limitations in replicating clinical procedures accurately and achieving broad applicability. This study aimed to develop novel mouse models of Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) surgeries specifically designed for T2DM research, utilizing simplified surgical techniques closely resembling clinical procedures. Eight-week-old C57/Bl6 mice, except for the Blank-Control group, were induced with T2DM by combining a high-fat diet and streptozotocin injection. RYGB involved creating a 10% gastric pouch, a 4-cm biliopancreatic limb (BL), and a 4-cm Roux limb (RL). Similarly, OAGB maintained a 10% gastric pouch and a 4-cm BL. To assess the efficacy of these models, we measured the body weight and fasting blood glucose (FBG) and conducted intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), and liver B-ultrasound, as well as a histopathological analysis of multiple organs 12weeks post-operation. The survival rates in the Blank-Control, T2DM-Sham, T2DM-RYGB, and T2DM-OAGB groups were 100% (6/6), 100% (6/6), 85.7% (6/7), and 100% (6/6), respectively. Both RYGB and OAGB surgeries similarly led to sustained weight loss, reduced the FBG levels, improved the IPGTT and ITT results, and alleviated the histopathological manifestations in multiple organs. The innovative mouse models of RYGB and OAGB surgeries effectively improve T2DM. Both surgeries demonstrate comparable efficacy in ameliorating T2DM, even when utilizing a gastric pouch of the same size and the same length of BL in OAGB.

Bariatric surgery improves postprandial VLDL kinetics and restores insulin mediated regulation of hepatic VLDL production.

Dyslipidemia in obesity results from excessive production and impaired clearance of triglyceride (TG)-rich lipoproteins, which is particularly pronounced in the postprandial state. Here, we investigated the impact of Roux-en-Y gastric bypass (RYGB) surgery on the postprandial VLDL1 and VLDL2 apoB and TG kinetics and their relationship with insulin responsiveness indices. 24 obese non-diabetic RYGB surgery patients underwent a lipoprotein kinetics study during a mixed meal test and a hyperinsulinemic-euglycemic clamp study before the surgery, and one year later. A physiologically based computational model was developed to investigate the impact of RYGB surgery and plasma insulin on postprandial VLDL kinetics. After the surgery, VLDL1 apoB and TG production rates were significantly decreased, whereas VLDL2 apoB and TG production rates remained unchanged. TG catabolic rate was increased in both VLDL1 and VLDL2 fractions, but only the VLDL2 apoB catabolic rate tended to increase. Furthermore, post-surgery VLDL1 apoB and TG production rates, but not VLDL2, were positively correlated with insulin resistance. Insulin-mediated stimulation of peripheral lipoprotein lipolysis was also improved after the surgery. In summary, RYGB resulted in a reduced hepatic VLDL1 production that correlated with reduced insulin resistance, an elevated VLDL2 clearance, and improved insulin sensitivity in lipoprotein lipolysis pathways.

Laparoscopic transcystic common bile duct exploration versus transgastric endoscopic retrograde cholangiography during cholecystectomy after Roux-en-Y gastric bypass.

Treatment of common bile duct (CBD) stones after Roux-en-Y gastric bypass (RYGB) poses a particular challenge given the altered anatomy and inability to perform a standard endoscopic retrograde cholangiogram (ERC). The optimal treatment strategy for intraoperatively encountered CBD stones in post-RYGB patients has not been established. To compare outcomes following laparoscopic transcystic common bile duct exploration (LTCBDE) and laparoscopy-assisted transgastric ERC for CBDs during cholecystectomy in RYGB-operated patients. Swedish nationwide multi-registry study. The Swedish Registry for Gallstone Surgery and ERCs, GallRiks (n = 215,670), and the Scandinavian Obesity Surgery Registry (SOReg) (n = 60,479) were cross-matched for cholecystectomies with intraoperatively encountered CBD stones in patients with previous RYGB surgery between 2011 and2020. Registry cross-matching found 550 patients. Both LTCBDE (n = 132) and transgastric ERC (n = 145) were comparable in terms of low rates of intraoperative adverse events (1% versus 2%) and postoperative adverse events within 30 days (16% versus 18%). LTCBDE required significantly shorter operating time (P = .005) by on average 31 minutes, 95% confidence interval (CI) [10.3-52.6], and was more often used for smaller stones <4 mm in size (30% versus 17%, P = .010). However, transgastric ERC was more often used in acute surgery (78% versus 63%, P = .006) and for larger stones >8 mm in size (25% versus 8%, P < .001). LTCBDE and transgastric ERC have similarly low complication rates for clearance of intraoperatively encountered CBD stones in RYGB-operated patients, but LTCBDE is faster while transgastric ERC is more often used in conjunction with larger bile duct stones.

Outcome of Gastric Bypass Surgery on Patients with Polycystic Ovary Syndrome: A Review.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is associated with obesity. The most effective method to achieve and maintain long-term weight loss is by the Roux-en-Y gastric bypass (RYGB). In this review, an overview about metabolic and PCOS-specific outcomes after RYGB in obese PCOS women is provided. The RYGB leads to an adequate excess weight loss and reduction in BMI in this patient population. Testosterone levels decline significantly at 6- and 12-months follow-up, as does the incidence of hirsutism and cycle irregularities. Data about fertility are scarce in this patient population. In conclusion, RYGB surgery seems to be an efficient treatment option for obese PCOS patients and leads to weight loss and improvements in metabolic parameters as well as in an improvement of PCOS-specific characteristics. However, larger prospective studies are warranted, which include all PCOS-specific outcome data in one patient population at the same time.

Severe Anemia in Sprague-Dawley Rats After Roux-en-Y Gastric Bypass Surgery.

Roux-en-Y gastric bypass (RYGB) surgery is one of the most commonly performed bariatric procedures for weight loss in humans. However, this procedure is not risk-free, and patients may experience complications that include small bowel obstruction, gastrointestinal bleeding, chronic diarrhea, ulcers, malnutrition, and anemia. In particular, anemia is a recognized long-term complication and can be severe. Rats have been used as a model to study the effects of gastric bypass surgeries. They can experience similar complications as people, but the development of severe anemia has not previously been reported in rats. We observed 2 cases of severe anemia in female Sprague-Dawley rats after RYGB surgery. These cases prompted us to further investigate the frequency and severity of anemia after RYGB in rats. Blood work and necropsies were performed on 9 additional female Sprague-Dawley rats (5 with RYGB, 4 with sham surgery). In these 9 rats, only one had signs of clinical anemia. These 3 anemic rats displayed moderate to severe pallor of the eyes and ears. Necropsy findings in anemic RYGB rats included pale internal organs and eccentric heart enlargement, which led to a significantly higher heart:body weight ratio in RYGB rats as compared with sham controls. Anemic rats had either a macrocytic normochromic anemia, consistent with vitamin B12 or folate deficiency, or microcytic hypochromic anemia, indicative of iron deficiency. Researchers who perform RYGB surgery in rats should be aware of the potential complication of severe anemia. Plans for the diagnosis and management of this complication and the development of criteria for humane endpoints for severe anemia are recommended as a refinement to these studies.

RYGB surgery has modest effects on intestinal morphology and gut hormone populations in the bypassed biliopancreatic limb but causes reciprocal changes in GLP-2 and PYY in the alimentary limb.

Roux-en-Y gastric-bypass (RYGB) induced alterations in intestinal morphology and gut-cell hormone expression profile in the bypassed biliopancreatic-limb (BPL) versus the alimentary-limbs (AL) are poorly characterised. This pilot study has therefore explored effects following RYGB in high-fat-diet (HFD) and normal-diet (ND) rats. Female Wistar rats (4-week-old) were fed HFD or ND for 23-weeks prior to RYGB or sham surgeries. Immunohistochemical analysis of excised tissue was conducted three-weeks post-surgery. After RYGB, intestinal morphology of the BPL in both HFD and ND groups was unchanged with exception of a small decrease in villi width in the ND-RYGB and crypt depth in the HFD-RYGB group. However, in the AL, villi width was decreased in ND-RYGB rats but increased in the HFD-RYGB group. In addition, crypt depth decreased after RYGB in the AL of HFD rats. GIP positive cells in either limb of both groups of rats were unchanged by RYGB. Similarly, there was little change in GLP-1 positive cells, apart from a small decrease of numbers in the villi of the BPL in HFD rats. RYGB increased GLP-2 cell numbers in the AL of ND-RYGB rats, including in both crypts and villi. This was associated with decreased numbers of cells expressing PYY in the AL of ND-RYGB rats. The BPL appears to maintain normal morphology and unchanged enteroendocrine cell populations despite being bypassed in RYGB-surgery. In contrast, in the AL, villi area is generally enhanced post-RYGB in ND rats with increased numbers of GLP-2 positive cells and decreased expression of PYY.

Roux-en-Y gastric bypass induces hepatic transcriptomic signatures and plasma metabolite changes indicative of improved cholesterol homeostasis

Roux-en-Y gastric bypass (RYGB), the most effective surgical procedure for weight loss, decreases obesity and ameliorates comorbidities, such as non-alcoholic fatty liver (NAFLD) and cardiovascular (CVD) diseases. Cholesterol is a major CVD risk factor and modulator of NAFLD development, and the liver tightly controls its metabolism. How RYGB surgery modulates systemic and hepatic cholesterol metabolism is still unclear. We studied the hepatic transcriptome of 26 patients with obesity but not diabetes before and 1 year after undergoing RYGB. In parallel, we measured quantitative changes in plasma cholesterol metabolites and bile acids (BAs). RYGB surgery improved systemic cholesterol metabolism and increased plasma total and primary BA levels. Transcriptomic analysis revealed specific alterations in the liver after RYGB, with the downregulation of a module of genes implicated in inflammation and the upregulation of three modules, one associated with BA metabolism. A dedicated analysis of hepatic genes related to cholesterol homeostasis pointed towards increased biliary cholesterol elimination after RYGB, associated with enhancement of the alternate, but not the classical, BA synthesis pathway. In parallel, alterations in the expression of genes involved in cholesterol uptake and intracellular trafficking indicate improved hepatic free cholesterol handling. Finally, RYGB decreased plasma markers of cholesterol synthesis, which correlated with an improvement in liver disease status after surgery. Our results identify specific regulatory effects of RYGB on inflammation and cholesterol metabolism. RYGB alters the hepatic transcriptome signature, likely improving liver cholesterol homeostasis. These gene regulatory effects are reflected by systemic post-surgery changes of cholesterol-related metabolites, corroborating the beneficial effects of RYGB on both hepatic and systemic cholesterol homeostasis. Roux-en-Y gastric bypass (RYGB) is a widely used bariatric surgery procedure with proven efficacy in body weight management, combatting cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). RYGB exerts many beneficial metabolic effects, by lowering plasma cholesterol and improving atherogenic dyslipidemia. Using a cohort of patients undergoing RYGB, studied before and 1 year after surgery, we analyzed how RYGB modulates hepatic and systemic cholesterol and bile acid metabolism. The results of our study provide important insights on the regulation of cholesterol homeostasis after RYGB and open avenues that could guide future monitoring and treatment strategies targeting CVD and NAFLD in obesity.

Abstract #1401957: Hypoglycemia in a Patient with Malnutrition After Bariatric Surgery and Cirrhosis from Alpha-1 Antitrypsin Deficiency

Hypoglycemia is rare in patients who do not have diabetes treated by insulin or insulin secretagogues. However, severe malnutrition can predispose to hypoglycemia through substrate limitation of gluconeogenesis and glycogen depletion, and severe hepatic insufficiency may lead to hypoglycemia due to reduced capacity for gluconeogenesis and synthesis and storage of glycogen. We report a case of hypoglycemia occurring in a patient with malnutrition after Roux-en-Y gastric bypass (RYGB) surgery and cirrhosis due to alpha1-antitrypsin (AAT) deficiency. Endocrinology was consulted to evaluate a 67-year-old female for possible hypoglycemia. Her history was notable for RYGB surgery and AAT deficiency complicated by cirrhosis. The patient reported a 3-y history of dizziness and palpitations that resolved after eating. BMI was 18 kg/m2, and bitemporal wasting and sarcopenia were observed. Markers of liver function were abnormal, including prothrombin time (16.3 sec, 11.7-14.7) and albumin level (2.2 g/dL, 3.5-5.7). GFR calculated to 81 mL/min/1.73 m2. During a diagnostic fast, plasma glucose fell to 47 mg/dL, and simultaneously measured insulin and C-peptide levels were 0.8 mIU/mL (expected < 3) and 1.4 ng/dL (expected < 0.6), respectively. Beta-hydroxybutyrate level was 0.1 mM (expected > 2.7). An insulin secretagogues panel, ACTH-stimulation test, and IGF-2 level were unremarkable. Malnutrition is a well-known risk factor for hypoglycemia, and approximately 5% of hospitalized patients with malnutrition experience hypoglycemia. Significant protein-energy malnutrition, though uncommon after RYGB, has been documented in nearly 5% of patients in some series. Severe hepatic insufficiency is also an independent risk factor for hypoglycemia, and 10-15% of patients with AAT deficiency develop hepatic injury due to accumulation of Z-type AAT polymers in the liver. Though the patient had advanced liver failure as indicated by elevated prothrombin time and inability to mount a ketogenic response to hypoglycemia, AAT deficiency induced cirrhosis alone has not been documented to cause hypoglycemia in adults. C-peptide is metabolized mostly by the kidneys, and the discrepancy between insulin and C-peptide levels was most likely due to impaired renal function, with GFR artifactually high due to low serum creatinine level from sarcopenia. This case of hypoglycemia is unusual because it was due to the co-occurrence of two unusual disorders – severe protein malnutrition following RYGB and cirrhosis due to AAT deficiency – and measurements of C-peptide and beta-hydroxybutyrate were confounded by the patient’s renal and hepatic function, respectively.

The impact of laparoscopic Roux-en-Y gastric bypass on sleep quality and duration after one year of follow-up

Several studies have shown the association between obesity and sleep. Roux-en-Y gastric bypass (RYGB) surgery may improve sleep disturbances in patients with obesity by influencing a variety of factors. This study aims to evaluate the impact of bariatric surgery on sleep quality. Patients with severe obesity referred to the obesity clinic of a center from September 2019 to October 2021 were collected. The patients were divided into two groups, depending on whether they underwent RYGB surgery. Medical comorbidities and self-report questionnaires regarding sleep quality, anxiety, and depression were collected at baseline and 1-year follow-up. 54 patients were included, including 25 in the bariatric surgery group and 29 in the control group. However, five patients in the RYGB surgery group and four patients in the control group were lost in the follow-up. Pittsburgh Sleep Quality Index (PSQI) was decreased from a mean of 7.7 to 3.8 in the bariatric surgery group (p-value<0.001). In contrast to the control group, the number of patients with obstructive sleep apnea was significantly reduced in the bariatric surgery group. We showed a significant improvement in sleep quality following RYGB surgery. Obstructive sleep apnea, obesity/overweight, and depressive symptoms significantly improved in our study. There is a lack of a better understanding of the association between these factors and sleep quality following surgery. Therefore, further studies are recommended regarding this issue.

Reduction of Plasma BCAAs following Roux-en-Y Gastric Bypass Surgery Is Primarily Mediated by FGF21.

Type 2 diabetes (T2D) is a challenging health concern worldwide. A lifestyle intervention to treat T2D is difficult to adhere, and the effectiveness of approved medications such as metformin, thiazolidinediones (TZDs), and sulfonylureas are suboptimal. On the other hand, bariatric procedures such as Roux-en-Y gastric bypass (RYGB) are being recognized for their remarkable ability to achieve diabetes remission, although the underlying mechanism is not clear. Recent evidence points to branched-chain amino acids (BCAAs) as a potential contributor to glucose impairment and insulin resistance. RYGB has been shown to effectively lower plasma BCAAs in insulin-resistant or T2D patients that may help improve glycemic control, but the underlying mechanism for BCAA reduction is not understood. Hence, we attempted to explore the mechanism by which RYGB reduces BCAAs. To this end, we randomized diet-induced obese (DIO) mice into three groups that underwent either sham or RYGB surgery or food restriction to match the weight of RYGB mice. We also included regular chow-diet-fed healthy mice as an additional control group. Here, we show that compared to sham surgery, RYGB in DIO mice markedly lowered serum BCAAs most likely by rescuing BCAA breakdown in both liver and white adipose tissues. Importantly, the restored BCAA metabolism following RYGB was independent of caloric intake. Fasting insulin and HOMA-IR were decreased as expected, and serum valine was strongly associated with insulin resistance. While gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are postulated to mediate various surgery-induced metabolic benefits, mice lacking these hormonal signals (GLP-1R/Y2R double KO) were still able to effectively lower plasma BCAAs and improve glucose tolerance, similar to mice with intact GLP-1 and PYY signaling. On the other hand, mice deficient in fibroblast growth factor 21 (FGF21), another candidate hormone implicated in enhanced glucoregulatory action following RYGB, failed to decrease plasma BCAAs and normalize hepatic BCAA degradation following surgery. This is the first study using an animal model to successfully recapitulate the RYGB-led reduction of circulating BCAAs observed in humans. Our findings unmasked a critical role of FGF21 in mediating the rescue of BCAA metabolism following surgery. It would be interesting to explore the possibility of whether RYGB-induced improvement in glucose homeostasis is partly through decreased BCAAs.

Red Meat Intake, Indole-3-Acetate, and Dorea longicatena Together Affect Insulin Resistance after Gastric Bypass

Roux-en-Y Gastric bypass (RYGB) promotes improvement in type 2 diabetes (T2D) shortly after surgery, with metabolic mechanisms yet to be elucidated. This study aimed to investigate the relationship between food intake, tryptophan metabolism, and gut microbiota on the glycemic control of obese T2D women after RYGB surgery. Twenty T2D women who underwent RYGB were evaluated before and three months after surgery. Food intake data were obtained by a seven-day food record and a food frequency questionnaire. Tryptophan metabolites were determined by untargeted metabolomic analysis, and the gut microbiota was determined by 16S rRNA sequencing. The glycemic outcomes were fasting blood glucose, HbA1C, HOMA-IR, and HOMA-beta. Linear regression models were applied to assess the associations between the changes in food intake, tryptophan metabolism, and gut microbiota on glycemic control after RYGB. All variables changed after RYGB (p < 0.05), except for tryptophan intake. Jointly, the variation in red meat intake, plasma indole-3-acetate, and Dorea longicatena was associated with postoperative HOMA-IR {R2 0.80, R2 adj 0.74; p < 0.01}. Red meat intake decreased three months after bariatric surgery while indole-3-acetate and Dorea longicatena increased in the same period. These combined variables were associated with better insulin resistance in T2D women after RYGB.

Revision of Vertical Banded Gastroplasty to Roux-En-Y Gastric Bypass with 2 Years of Follow-Up

Background: Due to weight regain and GIT symptoms associated with vertical banded gastroplasty (VBG), revisional surgery is necessary. Roux-en-Y gastric bypass (RYGB) is one of the best options as a revision procedure but comes with a high complication rate. Methods: This prospective study included 80 patients undergoing RYGB surgery at Ain Shams University Hospitals after failed VBG surgery, with up to 2 years of follow-up. Results: Eighty patients underwent RYGB correction after VBG. The mean age was 42 ± 6.45 (39–58) years and the mean preoperative body mass index was 45.46 ± 4.135 (38–55) kg/m². The median length of hospital stay for the patients was 4.78 ± 1.84 days. The early postoperative complication rate was 8.7% and the reoperation rate within 30 days was 3.75%, with no mortality. Leakage and bowel injury were detected in 2 patients. After an average follow-up of 2 years, the percentage of EWL was 64.47 ± 19.3, and complete resolution of VBG-related GIT symptoms was achieved in approximately all patients. Late complications occurred in 7.5% of patients, of whom 3.75% required surgery. Conclusion: Conversion to RYGB is feasible with a limited short-term complication and reoperation rate; long-term results show a nearly complete resolution of VBG-related symptoms and a statistically significant positive impact on weight loss.

Exploration of fMRI brain responses to oral sucrose after Roux-en-Y gastric bypass in obese yucatan minipigs in relationship with microbiota and metabolomics profiles

In most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut-brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control. An integrative study was performed after SHAM (n=8) or RYGBP (n=8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis. We showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP. This longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.

The PYY/Y2R-deficient male mouse is not protected from bone loss due to Roux-en-Y gastric bypass.

Peptide YY (PYY) is an anorexigenic gut hormone that also has anti-osteogenic effects, inhibiting osteoblastic activity and inducing catabolic effects. It has been postulated that increases in PYY after Roux-en-Y gastric bypass (RYGB) contribute to declines in bone mineral density (BMD) and increases in bone turnover. The aim of this study is to determine the role of the PYY Y2-receptor in mediating bone loss post-RYGB in mice. We compared adult male wildtype (WT) and PYY Y2 receptor-deficient (KO) C57BL/6 mice that received RYGB (WT: n=8; KO: n=9), with sham-operated mice (Sham; WT: n=9; KO: n=10) and mice that were food-restricted to match the weights of the RYGB-treated group (Weight-Matched, WM; WT: n=7; KO: n=5). RYGB or sham surgery was performed at 15-16weeks of age, and mice sacrificed 21weeks later. We characterized bone microarchitecture with micro-computed tomography (μCT) at the distal femur (trabecular) and femoral midshaft (cortical). Differences in body weight, bone microarchitecture and biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) were compared using 2-factor ANOVA with Tukey's adjustments for multiple comparisons. Body weights were similar in the WT-RYGB, WT-WM, KO-RYGB, and KO-WM: 41-44g; these groups weighed significantly less than the Sham surgery groups: 55-57g. Trabecular BMD was 31-43% lower in RYGB mice than either Sham or WM in WT and KO groups. This deficiency in trabecular bone was accompanied by a lower trabecular number (19%-23%), thickness (22%-30%) and increased trabecular spacing (25%-34%) in WT and KO groups (p<0.001 for all comparisons vs. RYGB). RYGB led to lower cortical thickness, cortical tissue mineral density, and cortical bone area fraction as compared to Sham and WM in WT and KO groups (p≤0.004 for all). There were no interactions between genotype and bone microarchitecture, with patterns of response to RYGB similar in both WT and KO groups. CTX and P1NP were significantly higher in RYGB mice than WM in WT and KO groups. PTH did not differ among groups. RYGB induced greater trabecular and cortical deficits and high bone turnover than observed in weight-matched mice, with a similar pattern in the WT and Y2RKO mice. Thus, skeletal effects of RYGB are independent of weight loss, and furthermore, PYY signaling through Y2R is not a key mediator of bone loss post-RYGB.

Mucosal and hormonal adaptations after Roux-en-Y gastric bypass.

The aim of this study was to perform a comprehensive literature review regarding the relevant hormonal and histologic changes observed after Roux-en-Y gastric bypass (RYGB). We aimed to describe the relevant hormonal (glucagon-like peptides 1 and 2 [GLP-1 and GLP-2], peptide YY [PYY], oxyntomodulin [OXM], bile acids [BA], cholecystokinin [CCK], ghrelin, glucagon, gastric inhibitory polypeptide [GIP], and amylin) profiles, as well as the histologic (mucosal cellular) adaptations happening after patients undergo RYGB. Our review compiles the current evidence and furthers the understanding of the rationale behind the food intake regulatory adaptations occurring after RYGB surgery. We identify gaps in the literature where the potential for future investigations and therapeutics may lie. We performed a comprehensive database search without language restrictions looking for RYGB bariatric surgery outcomes in patients with pre- and postoperative blood work hormonal profiling and/or gut mucosal biopsies. We gathered the relevant study results and describe them in this review. Where human findings were lacking, we included animal model studies. The amalgamation of physiologic, metabolic, and cellular adaptations following RYGB is yet to be fully characterized. This constitutes a fundamental aspiration for enhancing and individualizing obesity therapy.