RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women.

Retinol-binding protein-4 (RBP4) is elevated in serum and adipose tissue (AT) in obesity-induced insulin resistance and correlates inversely with insulin-stimulated glucose disposal. But its role in insulin-mediated suppression of lipolysis, free fatty acids (FFA), and endogenous glucose production (EGP) in humans is unknown. RBP4 mRNA or protein levels were higher in liver, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in morbidly obese subjects undergoing Roux-en-Y gastric bypass surgery compared to lean controls undergoing elective laparoscopic cholecystectomy. RBP4 mRNA expression in SAT correlated with the expression of several macrophage and other inflammation markers. Serum RBP4 levels correlated inversely with glucose disposal and insulin-mediated suppression of lipolysis, FFA, and EGP. Mechanistically, RBP4 treatment of human adipocytes in vitro directly stimulated basal lipolysis. Treatment of adipocytes with conditioned media from RBP4-activated macrophages markedly increased basal lipolysis and impaired insulin-mediated lipolysis suppression. RBP4 treatment of macrophages increased TNFα production. These data suggest that elevated serum or adipose tissue RBP4 levels in morbidly obese subjects may cause hepatic and systemic insulin resistance by stimulating basal lipolysis and by activating macrophages in adipose tissue, resulting in release of pro-inflammatory cytokines that impair lipolysis suppression. While we have demonstrated this mechanism in human adipocytes in vitro, and correlations from our flux studies in humans strongly support this, further studies are needed to determine whether this mechanism explains RBP4-induced insulin resistance in humans.

Can a laparoscopic Roux-en-Y gastric bypass be safely performed by surgical residents in a bariatric center-of-excellence? The learning curve of surgical residents in bariatric surgery.

BACKGROUND: A learning curve (LC) is a graphic display of the number of consecutive procedures performed necessary to reach competence and is defined by complications and duration of surgery (DOS). There is little evidence on the LC of surgical residents in bariatric surgery. Aim of the study is to evaluate whether the laparoscopic Roux-en-Y gastric bypass (LRYGB) can be safely performed by surgical residents, to evaluate the LC of surgical residents for LRYGB and to assess whether surgical residents fit in the LC of the bariatric center which has been established by their proctors. METHODS: Records of all 3389 consecutive primary LRYGB patients, operated between December 2007 and January 2016 in a bariatric center-of-excellence in Amsterdam, were reviewed. Differences in DOS were assessed by means of a linear regression model. Differences in complications (classified as Clavien-Dindo ≥ 2) were evaluated with the χ 2 or the Fisher exact test. Cases were clustered in groups of 70 for comparison and reported for residents with ≥70 cases as primary surgeon. RESULTS: Four surgeons (S1-4) and three residents (R1-3) performed 2690 (88.2%) and 361 (11.8%) of 3051 LRYGBs, respectively. Median (IQR) DOS was 52.0 (42.0-65.0) min for S1-4 versus 53.0 (46.0-63.0) min for R1-3 (p = 0.52). The LC of R1-3 in their first 70 cases (n = 210) differs significantly from the individual (n = 70) LCs of surgeon 1, 2, and 3, with remarkably shorter DOS for the residents (adjusted p < 0.0001; p < 0.001 and p = 0.0002, respectively) and the same amount of surgical complications 5.1% (137/2690) for S1-4 versus 3.0% (11/361) for R1-3 (p = 0.089). CONCLUSION: Laparoscopic Roux-en-Y gastric bypass can be safely performed by surgical residents under supervision of experienced bariatric surgeons. Surgical residents benefit from the experience of their proctors and they fit faultlessly in the LC of the surgical team, as set out by their proctors in a large bariatric center-of-excellence.

A novel fully covered double-bump stent for staple line leaks after bariatric surgery: a retrospective analysis.

BACKGROUND: Staple line leakage after bariatric surgery can be treated by endoscopic placement of a self-expandable stent. The success rate of stent placement is generally high, but migration is a frequent adverse event that hampers successful treatment. The Niti-S Beta stent is a fully covered double-bump stent that was specifically designed to prevent migration. This study aimed to evaluate the effectiveness and adverse event rate of the Niti-S Beta stent. METHODS: A retrospective study was performed in three high-volume bariatric centers. All consecutive patients between 2009 and 2016 who underwent placement of a Beta stent for staple line leakage were included. Primary outcome was resolution of the leakage; secondary outcome was the adverse event rate including migration. RESULTS: Thirty-eight patients were included. Twenty-five (66%) had resolution of the leakage. Success rate was higher in patients who were treated with implantation of a Beta stent as initial treatment (100%) than in patients who were treated with a stent after revisional surgery had failed (55%, p = 0.013). Migration occurred in 12 patients (32%). There were two severe adverse events requiring surgical intervention, including a bleeding from an aorto-esophageal fistula. CONCLUSIONS: The success rate and the migration rate of the Beta stent seem comparable to other stents in this retrospective study. Despite the novel double-bump structure of the stent, the migration rate does not seem to be decreased.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: study protocol for a randomized controlled trial (UPGRADE trial).

BACKGROUND: The number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA. METHODS: A randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed. DISCUSSION: The UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective. TRIAL REGISTRATION: Netherlands Trial Register (trialregister.nl) 6135 . Date registered: 21-Nov-2016.

Bridging the gap between gastric pouch and jejunum: a bariatric nightmare.

BACKGROUND: Even in a large volume bariatric centre, bariatric surgeons are sometimes confronted with intraoperative anatomical challenges which force even the most experienced surgeon into a pioneering position. In this video we present how a large gap of approximately 8 cm is bridged by applying several techniques that are not part of our standardized surgical procedure. CASE PRESENTATION: After creation of a 20 mL gastric pouch we discovered that the alimentary limb could not be advanced further cranially due to a very short a thick jejunal mesentery in a 49 year old male patient during laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. By dissecting the gastro-oesophageal junction form the crus, stretching the gastric pouch, transecting the jejunal mesentery, using a retrocolic/retrogastric route, and creating a fully hand-sewn gastrojejunostomy we were able to safely complete the LRYGB. Drains were left near the gastrojejunostomy and the patient was kept nil by mouth for 5 days. On the 5th postoperative day radiographic swallow series were obtained which revealed no sign of leakage. The patient was discharged in good clinical condition on the 6th postoperative day. To date, no complications have occurred. Weight loss results are -31.5 % of the preoperative total body weight. CONCLUSIONS: When confronted with a large distance between the gastric pouch and the alimentary limb, several techniques presented in this video may be of aid to the bariatric surgeon. We stress that only experienced bariatric surgeon should embark on these techniques. Inspecting the alimentary limb before the creation of the gastric pouch may prevent the need for such complex techniques.

Differences in Psychological Health and Weight Loss after Bariatric Metabolic Surgery between Patients with and without Pain Syndromes.

PURPOSE: Chronic pain and obesity often co-occur, negatively affecting one another and psychological wellbeing. Pain and psychological wellbeing improve after bariatric metabolic surgery (BMS), however, it is unknown whether psychological wellbeing improves differently after weight loss between patients with and without chronic pain. We investigated whether weight loss is associated with greater psychological wellbeing and functioning change after BMS, comparing patients with and without preoperative pain syndromes. METHODS: Depression, health-related quality of life, self-esteem, self-efficacy to exercise and controlling eating behaviours, physical activity, and food cravings were measured before and 24 months after BMS among 276 patients with obesity. The presence of preoperative chronic pain syndromes was examined as a moderator for the relationship between 24-month weight loss and changes in psychological outcomes. RESULTS: Chronic pain syndromes were present among 46% of patients. Weight loss was associated with greater improvement in health-related quality of life, self-efficacy to exercise and controlling eating behaviours, self-esteem and greater amelioration in food cravings. Pain syndromes only moderated negatively the relationship between the postoperative weight loss and change in self-efficacy to control eating behaviours (b = -0.49, CI [-0.88,-0.12]). CONCLUSION: Patients with and without chronic pain showed similar improvements in weight and psychological wellbeing and behaviours after BMS. The relationship between weight loss and the improvement of self-efficacy to control eating behaviours was weaker among patients with chronic pain syndrome. Further work, measuring pain severity over time, is needed to shed light on the mechanism underlying pain and postoperative change in psychological wellbeing and weight loss.

Alterations in bile acid kinetics after bariatric surgery in patients with obesity with or without type 2 diabetes.

BACKGROUND: Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking. METHODS: In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort. FINDINGS: We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort. INTERPRETATION: Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission. FUNDING: Novo Nordisk Fonden, Leducq Foundation, Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, the ALF-agreement, ZonMw.

Variation in HbA1c in Patients with Obesity and type 2 Diabetes Mellitus 12 months after Laparoscopic One-Anastomosis Gastric Bypass and Laparoscopic Roux-en-Y Gastric Bypass: a Retrospective Matched Cohort Study.

BACKGROUND: Glycemic control is an important goal of bariatric surgery in patients with type 2 diabetes mellitus (T2DM) and obesity. The laparoscopic one-anastomosis gastric bypass (OAGB) has potential metabolic benefits over the laparoscopic Roux-en-Y gastric bypass (RYGB). Aim of this study is to examine whether RYGB or OAGB grants better glycemic control 12 months post-surgery. METHODS: For this retrospective cohort study, patients with T2DM and obesity, who underwent primary OAGB between 2008 and 2017 were reviewed. For each OAGB patient, three primary RYGB patients were matched for age, gender and body mass index (BMI). Glycemic control was expressed by the glycated hemoglobin (HbA1c), which was measured pre- and 12 months post-operatively. Weight loss was reported in percentage total weight loss (%TWL). RESULTS: A total of 152 patients, of whom 38 had OAGB and 114 RYGB, were included. Mean (standard deviation (SD)) HbA1c was 7.49 (1.51)% in the OAGB group and 7.56(1.23)% in the RYGB group at baseline. Twelve months after surgery the mean (SD) HbA1c dropped to 5.73 (0.71)% after OAGB and 6.09 (0.76)% after RYGB (adjusted p = 0.011). The mean (SD) BMI was reduced from 42.5(6.3) kg/m2 to 29.6(4.7) kg/m2 after OAGB and 42.3(5.8) kg/m2 to 29.9 (4.5) kg/m2 after RYGB; reflecting 30.3 (6.8) %TWL post-OAGB and 29.0 (7.3) %TWL post-RYGB (p = 0.34). CONCLUSION: This study indicates that OAGB leads to lower HbA1c one year after surgery compared to RYGB, without a difference in weight loss. Prospective (randomized) studies are needed to ascertain the most optimal metabolic treatment for patients with obesity and T2DM.

The burden of abdominal pain after bariatric surgery in terms of diagnostic testing: the OPERATE study.

BACKGROUND: Abdominal pain after bariatric surgery (BS) is frequently observed. Despite numerous diagnostic tests, the cause of abdominal pain is not always found. OBJECTIVES: To quantify type and number of diagnostic tests performed in patients with abdominal pain after BS and evaluate the burden and their yield in the diagnostic process. SETTING: A bariatric center in the Netherlands. METHODS: In this prospective study, we included patients who presented with abdominal pain after BS between December 1, 2020, and December 1, 2021. All diagnostic tests and reoperations performed during one episode of abdominal pain were scored using a standardized protocol. RESULTS: A total of 441 patients were included; 401 (90.9%) were female, median time after BS was 37.0 months (IQR, 11.0-66.0) and mean percentage total weight loss was 31.41 (SD, 10.53). In total, 715 diagnostic tests were performed, of which 355 were abdominal CT scans, 155 were ultrasounds, and 106 were gastroscopies. These tests yielded a possible explanation for the pain in 40.2% of CT scans, 45.3% of ultrasounds, and 34.7% of gastroscopies. The diagnoses of internal herniation, ileus, and nephrolithiasis generally required only 1 diagnostic test, whereas patients with anterior cutaneous nerve entrapment syndrome, irritable bowel syndrome, and constipation required several tests before diagnosis. Even after several negative tests, a diagnosis was still found in the subsequent test: 86.7% of patients with 5 or more tests had a definitive diagnoses. Reoperations were performed in 37.2% of patients. CONCLUSION: The diagnostic burden in patients with abdominal pain following BS is high. The most frequently performed diagnostic test is an abdominal CT scan, yielding the highest number of diagnoses in these patients.

Ursodeoxycholic Acid Use After Bariatric Surgery: Effects on Metabolic and Inflammatory Blood Markers.

BACKGROUND: In addition to the reduction of symptomatic gallstone disease, ursodeoxycholic acid (UDCA) might also have beneficial metabolic effects after bariatric surgery. We examined the impact of UDCA on liver enzymes, hemoglobin A1c (HbA1c), lipids, and inflammation markers. METHODS: Patients in the UPGRADE trial (placebo-controlled, double-blind) were randomized between UDCA 900 mg daily or placebo pills for 6 months after bariatric surgery. Patients without blood measurements pre- or 6 months postoperatively were excluded. The change in liver enzymes, Hba1c, lipids, and inflammation markers after surgery were compared between the UDCA and placebo group, followed by a postoperative cross-sectional comparison. RESULTS: In total, 513 patients were included (age [mean ± SD] 45.6 ± 10.7 years; 79% female). Preoperative blood values did not differ between UDCA (n = 266) and placebo (n = 247) groups. Increase of alkaline phosphatase (ALP) was greater in the UDCA group (mean difference 3.81 U/l [95%CI 0.50 7.12]). Change in other liver enzymes, HbA1c, lipids, and CRP levels did not differ. Postoperative cross-sectional comparison in 316 adherent patients also revealed a higher total cholesterol (mean difference 0.25 mg/dl [95%CI 0.07-0.42]), lower aspartate aminotransferase (mean difference -3.12 U/l [-5.16 - -1.08]), and lower alanine aminotransferase level (mean difference -5.89 U/l [-9.41 - -2.37]) in the UDCA group. CONCLUSION: UDCA treatment leads to a higher, but clinically irrelevant increase in ALP level in patients 6 months after bariatric surgery. No other changes in metabolic or inflammatory markers were observed. Except for the reduction of gallstone formation, UDCA has no effects after bariatric surgery.

The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery.

Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (ß = -0.72, p = 1 × 10-5) and in response to fiber supplementation (ß = -0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10-4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.

Compensatory intestinal antibody response against pro-inflammatory microbiota after bariatric surgery.

Obesity and type 2 diabetes (T2D) are growing burdens for individuals and the health-care system. Bariatric surgery is an efficient, but drastic treatment to reduce body weight, normalize glucose values, and reduce low-grade inflammation. The gut microbiome, which is in part controlled by intestinal antibodies, such as IgA, is involved in the development of both conditions. Knowledge of the effect of bariatric surgery on systemic and intestinal antibody response is limited. Here, we determined the fecal antibody and gut microbiome response in 40 T2D and non-diabetic (ND) obese individuals that underwent bariatric surgery (N = 40). Body weight, fasting glucose concentrations and inflammatory parameters decreased after bariatric surgery, whereas pro-inflammatory bacterial species such as lipopolysaccharide (LPS), and flagellin increased in the feces. Simultaneously, concentrations of LPS- and flagellin-specific intestinal IgA levels increased with the majority of pro-inflammatory bacteria coated with IgA after surgery. Finally, serum antibodies decreased in both groups, along with a lower inflammatory tone. We conclude that intestinal rearrangement by bariatric surgery leads to expansion of typical pro-inflammatory bacteria, which may be compensated by an improved antibody response. Although further evidence and mechanistic insights are needed, we postulate that this apparent compensatory antibody response might help to reduce systemic inflammation by neutralizing intestinal immunogenic components and thereby enhance intestinal barrier function after bariatric surgery.

Psychological functioning and well-being before and after bariatric surgery; what is the benefit of being self-compassionate?

OBJECTIVE: To investigate whether patients' psychological well-being (depression, quality of life, body image satisfaction) and functioning (self-efficacy for eating and exercising behaviours and food cravings) improve 12 months after bariatric surgery and whether self-compassion is associated with better psychological outcomes and lower weight after bariatric surgery. DESIGN: Longitudinal, prospective observational study. METHODS: Bariatric patients (n = 126, 77.8% female, 46.4 ± 10.8 years) completed the Self-compassion Scale, Center for Epidemiology Studies Depression Scale, Impact of Weight on Quality-of-Life questionnaire, Body Image Scale, Weight Efficacy Lifestyle Questionnaire, Spinal Cord Injury Exercise Self-Efficacy Scale, and G-Food Craving Questionnaire pre-operatively and 12 months post-operatively. A medical professional measured patients' weight during each assessment. Data were analysed using repeated measures t-tests and multivariate regression analyses with Benjamini-Hochberg correction for multiple testing. RESULTS: Patients' BMI, depression, and food cravings decreased significantly after surgery while quality of life, body image satisfaction, and self-efficacy to exercise improved. Higher self-compassion was associated with lower post-operative depression, greater quality of life, higher body image satisfaction, and better self-efficacy for eating behaviours (p-values <.05) but not with post-operative BMI, self-efficacy to exercise, or food cravings. CONCLUSIONS: Even though pre-operative self-compassion was not directly associated with a lower 12-month post-operative BMI, it had a positive relationship with patients' post-operative well-being and self-efficacy for controlling eating behaviour. In turn, this could help patients to manage their health long after bariatric surgery. Further work regarding the role of self-compassion on long-term health outcomes would be worthwhile.

Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration.

Obesity and diabetes are associated with inflammation and altered plasma levels of several metabolites, which may be involved in disease progression. Some metabolites can activate G protein-coupled receptors (GPCRs) expressed on immune cells where they can modulate metabolic inflammation. Here, we find that 3-hydroxydecanoate is enriched in the circulation of obese individuals with type 2 diabetes (T2D) compared with nondiabetic controls. Administration of 3-hydroxydecanoate to mice promotes immune cell recruitment to adipose tissue, which was associated with adipose inflammation and increased fasting insulin levels. Furthermore, we demonstrate that 3-hydroxydecanoate stimulates migration of primary human and mouse neutrophils, but not monocytes, through GPR84 and Gαi signaling in vitro. Our findings indicate that 3-hydroxydecanoate is a T2D-associated metabolite that increases inflammatory responses and may contribute to the chronic inflammation observed in diabetes.

Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity.

AIMS: Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. MATERIAL AND METHODS: Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m2) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. RESULTS: Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. CONCLUSIONS: Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.

Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts.

Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors and may contribute to development of type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). In this article, we investigated whether chronically elevated insulin levels are associated with cellular senescence in the human liver. In 107 individuals undergoing bariatric surgery, hepatic senescence markers were assessed by immunohistochemistry as well as transcriptomics. A subset of 180 participants from the ongoing Finnish Kuopio OBesity Surgery (KOBS) study was used as validation cohort. We found plasma insulin to be highly associated with various markers of cellular senescence in liver tissue. The liver transcriptome of individuals with high insulin revealed significant upregulation of several genes associated with senescence: p21, TGFß, PI3K, HLA-G, IL8, p38, Ras, and E2F. Insulin associated with hepatic senescence independently of NAFLD and plasma glucose. By using transcriptomic data from the KOBS study, we could validate the association of insulin with p21 in the liver. Our results support a potential role for hyperinsulinemia in induction of cellular senescence in the liver. These findings suggest possible benefits of lowering insulin levels in obese individuals with insulin resistance.

Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction.

Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.

What Is Weight Loss After Bariatric Surgery Expressed in Percentage Total Weight Loss (%TWL)? A Systematic Review.

Percentage total weight loss (%TWL) might be better than percentage excess weight loss to express weight loss in bariatric surgery. In this systematic review, performed according to the PRISMA statement, results of laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB) are assessed in %TWL. A total of 13,426 studies were screened and 49 included, reporting data of 24,760 patients. The results show that, despite limiting data, LRYGB is favorable over LSG in terms of weight loss in short-term follow-up. Although recent guidelines recommend to use %TWL when reporting outcome in bariatric surgery, this study shows that there is still insufficient quality data in %TWL, especially on LSG. The use of %TWL as the primary outcome measure in bariatric surgery should be encouraged.

Reporting Weight Loss 2021: Position Statement of the Dutch Society for Metabolic and Bariatric Surgery (DSMBS).

Prevailing recommendations on reporting weight loss after bariatric and metabolic surgery are not evidence-based. They promote the outcome metric percentage excess weight loss (%EWL), sometimes indicated as percentage excess body mass index loss (%EBMIL). Many studies proved that this popular outcome measure, in contrast to other weight loss metrics, is inaccurate and error-sensitive when comparing weight loss within and between studies. It is inappropriate for assessing poor weight loss response and weight regain as well. The percentage (total) weight loss metric is the best alternative. The Dutch Society for Metabolic and Bariatric Surgery (DSMBS) recommends to stop using the %EWL (or %EBMIL) metric as primary outcome measure in all cases and calls on the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) to propagate this evidence-based recommendation.

Interpretation of laboratory results after gastric bypass surgery: the effects of weight loss and time on 30 blood tests in a 5-year follow-up program.

BACKGROUND: Long-term follow-up with blood tests is essential for bariatric surgery to be a successful treatment for obesity and related co-morbidities. Adverse effects, deficiencies, and metabolic improvements need to be controlled. OBJECTIVE: We investigated the effects of time and weight loss on laboratory results in each postoperative phase after laparoscopic Roux-en-Y gastric bypass (LRYGB). SETTING: Bariatric center of excellence, general hospital, Netherlands. METHODS: We retrospectively evaluated results of 30 blood tests, preoperatively and at 6 months, 1 year, 2 years, and 5 years after LRYGB. The 2019 Dutch bariatric chart was used to define weight loss responses as outstanding (>p[percentile curve]+1 SD), average (p+1 SD to p-1 SD), and poor (