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.

Health-related quality of life after sleeve gastrectomy equal to Roux-en-Y gastric bypass patients?

PURPOSE: Sleeve gastrectomy (SG) is the most popular type of bariatric surgery. It has often been compared to Roux-en-Y gastric bypass (RYGB) in terms of clinical outcomes. However, health-related quality of life (HRQoL) has been sparsely studied after SG. The goal was to study HRQoL after SG using a generic (RAND-36) and an obesity-specific (impact of weight on quality of life-lite, IWQOL-lite) questionnaire and to compare the results with RYGB. METHODS: HRQoL and weight were measured before and 9, 15, and 24 months after surgery. RAND-36 physical health summary (PHS) and mental health summary (MHS), and IWQOL-lite total score were calculated. A mixed model analysis was conducted to study the change in HRQoL and compare SG with RYGB. RESULTS: A total of 219 patients (8.7%) underwent a SG and 2309 patients (91.3%) a RYGB. PHS, MHS, and IWQOL-lite significantly improved after SG when comparing baseline to all follow-up moments (p < 0.001 in all). There were no significant differences when comparing SG with RYGB: change in PHS (ß - 0.10, 95% CI - 1.24 to 1.04, p = 0.861), MHS (ß - 0.51, 95% CI - 1.56 to 0.52, p = 0.330), and IWQOL-lite (ß 0.310, 95% CI - 0.85 to 1.47, p = 0.601). CONCLUSION: HRQoL significantly improved after SG. In the included populations, weight loss was comparable and the extent to which HRQoL improved did not differ between SG and RYGB, when measured with the RAND-36 or IWQOL-lite. This might be partly caused by the fact that these questionnaires do not assess specific bariatric HRQoL and/or complaints.

Changes in glycemic control and body weight after explantation of the duodenal-jejunal bypass liner.

BACKGROUND AND AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device that induces weight loss and improves glycemic control in patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to assess the effects of DJBL explantation on glycemic control and body weight. METHODS: This prospective, observational study included only patients with T2DM who had the DJBL implanted for at least 6 months and had a follow-up of at least 12 months after explantation. The primary endpoints were changes in glycosylated hemoglobin A1c (HbA1c) and body weight during the 12 months after explantation. Secondary endpoints were changes in fasting plasma glucose, blood pressure, and plasma lipid levels. RESULTS: In total, 59 patients completed the 12-month follow-up after explantation. During this period body weight increased by 5.6 (standard deviation, 6.4) kg (P < .001) and HbA1c rose from 65 (SD 17) to 70 (SD 20) mmol/mol (P < .001). However, body weight remained 8.0 (SD 8.6) kg (P < .001) lower than before implantation, that is, corresponding to a net total body weight loss of 7.4% (SD 7.6) (P < .001). Although HbA1c was significantly higher 12 months after explantation compared with baseline and the mean daily dose of insulin used was comparable, the number of patients on insulin remained significantly lower than before implantation. CONCLUSIONS: Explantation of the DJBL is associated with weight gain and worsening of glycemic control, although some beneficial effects remained detectable 12 months after explantation. A change in strategy is needed to preserve the beneficial effects of DJBL treatment. (Clinical trial registration number: 746∖100111.).

A short or a long Roux limb in gastric bypass surgery: does it matter?

BACKGROUND: The Roux-en-Y gastric bypass (RYGB) still remains the gold standard in bariatric surgery. However, no consensus exists on the optimal limb lengths to induce maximum weight reduction. The aim of the present study was to assess the effect of a longer alimentary limb (AL) length on weight reduction after RYGB. METHODS: A retrospective analysis of a prospectively collected database of patients who underwent a primary laparoscopic RYGB between January 2001 and March 2011 was performed. Patients received a short AL (SAL; 100 cm) or a long AL (LAL; 150 cm). Primary outcome was weight loss, and secondary outcomes were short- and long-term complication rates. RESULTS: A total of 768 patients received a RYGB during the study period. Of these, 730 consecutive patients were included for long-term analysis and had a mean follow-up (FU) of 37 ± 26 [range 0-120] months; 360 (47 %) patients received a SAL RYGB. Overall %TBWL was 33 ± 9 % after 2 years (FU 74 %) and 28 ± 12 % after 5 years (FU 20 %). No significant differences in %TBWL were found between SAL RYGB and LAL RYGB during the study period. The 30-day mortality rate was 0.13, 9 % overall short-term complication rate and 19 % cumulative long-term complication rate. No differences in complications were found between SAL and LAL RYGB patients. CONCLUSION: Lengthening of the alimentary limb from 100 to 150 cm did not affect post-RYGB weight loss. Overall complication rates were low and comparable in this series of RYGB patients.

Weight reduction and improvement in diabetes by the duodenal-jejunal bypass liner: a 198 patient cohort study.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic treatment for patients with type 2 diabetes mellitus (T2DM) and (morbid) obesity. The aim of the current study was to determine its efficacy and safety profile. METHODS: Inclusion criteria for treatment with a DJBL were: age 18-70 years, BMI 28-45 kg/m2, and T2DM with a HbA1c > 48 mmol/mol. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included changes in blood pressure, lipids, and anti-diabetic medication. Predictive factors for success of treatment with the DJBL were determined. RESULTS: Between 2011 and 2014, 185 out of 198 patients successfully underwent a DJBL implantation procedure, with an intended implantation time of 12 months. In these 185 patients, body weight decreased by 12.8 ± 8.0 kg (total body weight loss of 11.9 ± 6.9 %, p < 0.001), HbA1c decreased from 67 to 61 mmol/mol (p < 0.001) despite a reduction in anti-diabetic medication, and blood pressure and serum lipid levels all decreased. In total, 57 (31 %) DJBLs were explanted early after a median duration of 33 weeks. Adverse events occurred in 17 % of patients. C-peptide ≥1.0 nmol/L and body weight ≥107 kg at screening were independent predictive factors for success. CONCLUSIONS: Treatment with the DJBL in T2DM patients with (morbid) obesity results in improvement in glucose control, a reduction in anti-diabetic medication, and significant weight loss. The largest changes are observed within the first 3-6 months. Initial C-peptide levels and body weight may help to select patients with the greatest chance of success.

Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer.

BACKGROUND: Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up. METHODS: Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842). RESULTS: In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4). CONCLUSIONS: Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.

Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.

BACKGROUND & AIMS: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA alters hepatic expression of many genes. However, no data are available on the effects of OCA in the human liver. Here we generated gene expression profiles in human precision cut liver slices (hPCLS) after treatment with OCA. METHODS: hPCLS were incubated with OCA for 24 h. Wild-type or FXR(-/-) mice received OCA or vehicle by oral gavage for 7 days. RESULTS: Transcriptomic analysis showed that well-known FXR target genes, including NR0B2 (SHP), ABCB11 (BSEP), SLC51A (OSTα) and SLC51B (OSTß), and ABCB4 (MDR3) are regulated by OCA in hPCLS. Ingenuity pathway analysis confirmed that 'FXR/RXR activation' is the most significantly changed pathway upon OCA treatment. Comparison of gene expression profiles in hPCLS and mouse livers identified 18 common potential FXR targets. ChIP-sequencing in mouse liver confirmed FXR binding to IR1 sequences of Akap13, Cgnl1, Dyrk3, Pdia5, Ppp1r3b and Tbx6. CONCLUSIONS: Our study shows that hPCLS respond to OCA treatment by upregulating well-known FXR target genes, demonstrating its suitability to study FXR-mediated gene regulation. We identified six novel bona-fide FXR target genes in both mouse and human liver. Finally, we discuss a possible explanation for changes in high or low density lipoprotein observed in NASH and primary biliary cholangitis patients treated with OCA based on the genomic expression profile in hPCLS.

The impact of PPARα activation on whole genome gene expression in human precision cut liver slices.

BACKGROUND: Studies in mice have shown that PPARα is an important regulator of lipid metabolism in liver and key transcription factor involved in the adaptive response to fasting. However, much less is known about the role of PPARα in human liver. METHODS: Here we set out to study the function of PPARα in human liver via analysis of whole genome gene regulation in human liver slices treated with the PPARα agonist Wy14643. RESULTS: Quantitative PCR indicated that PPARα is well expressed in human liver and human liver slices and that the classical PPARα targets PLIN2, VLDLR, ANGPTL4, CPT1A and PDK4 are robustly induced by PPARα activation. Transcriptomics analysis indicated that 617 genes were upregulated and 665 genes were downregulated by PPARα activation (q value < 0.05). Many genes induced by PPARα activation were involved in lipid metabolism (ACSL5, AGPAT9, FADS1, SLC27A4), xenobiotic metabolism (POR, ABCC2, CYP3A5) or the unfolded protein response, whereas most of the downregulated genes were involved in immune-related pathways. Among the most highly repressed genes upon PPARα activation were several chemokines (e.g. CXCL9-11, CCL8, CX3CL1, CXCL6), interferon γ-induced genes (e.g. IFITM1, IFIT1, IFIT2, IFIT3) and numerous other immune-related genes (e.g. TLR3, NOS2, and LCN2). Comparative analysis of gene regulation by Wy14643 between human liver slices and primary human hepatocytes showed that down-regulation of gene expression by PPARα is much better captured by liver slices as compared to primary hepatocytes. In particular, PPARα activation markedly suppressed immunity/inflammation-related genes in human liver slices but not in primary hepatocytes. Finally, several putative new target genes of PPARα were identified that were commonly induced by PPARα activation in the two human liver model systems, including TSKU, RHOF, CA12 and VSIG10L. CONCLUSION: Our paper demonstrates the suitability and superiority of human liver slices over primary hepatocytes for studying the functional role of PPARα in human liver. Our data underscore the major role of PPARα in regulation of hepatic lipid and xenobiotic metabolism in human liver and reveal a marked immuno-suppressive/anti-inflammatory effect of PPARα in human liver slices that may be therapeutically relevant for non-alcoholic fatty liver disease.

Safety experience with the duodenal-jejunal bypass liner: an endoscopic treatment for diabetes and obesity.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is a new, device-based endoscopic treatment for type 2 diabetes mellitus (T2DM) and obesity. OBJECTIVE: To report serious safety events of subjects treated with the DJBL while offering a simple guideline to mitigate risk. DESIGN: Single-center observational study. SETTING: Tertiary referral center. PATIENTS: For commercial use, patients were eligible for implantation of the DJBL when they met the following criteria: age 18 to 65 years, body mass index 28 to 45 kg/m(2), T2DM, and negative serum Helicobacter pylori test. INTERVENTIONS: Endoscopic implantation of the DJBL. MAIN OUTCOME MEASUREMENTS: Adverse events, serious adverse events, early explantation. RESULTS: Between October 2007 and January 2014, 152 of 165 planned implantations (92%) and 94 explantations were performed in our center. Significant weight loss and improvement in T2DM and other cardiovascular parameters were achieved. Early removal of the device occurred because of persistent GI symptoms in 16 patients (11%). Serious adverse events were observed in a subset of patients: 7 GI bleeds, 5 of which required early removal; 2 cases of pancreatitis; 1 case of hepatic abscess; and 1 obstruction of the sleeve. Explantation resulted in an esophageal tear in 2 cases. LIMITATIONS: Single-center study. CONCLUSION: The DJBL improves glycemic control while causing weight loss. The safety profile of the DJBL demonstrates a reasonable tolerability profile. However, serious safety adverse events can occur. Patient selection, expert use of the device at placement and removal, and the supportive care of an experienced multidisciplinary team are key for safe and effective use of the DJBL.

The effect of the endoscopic duodenal-jejunal bypass liner on obesity and type 2 diabetes mellitus, a multicenter randomized controlled trial.

OBJECTIVE: Investigate the safety and efficacy of 6 months' duodenal-jejunal bypass liner (DJBL) treatment in comparison with dietary intervention for obesity and type 2 diabetes mellitus (T2DM). BACKGROUND: The DJBL is a bariatric procedure involving an impermeable sleeve that is delivered endoscopically in the proximal intestine. This procedure not only is less invasive than conventional surgical techniques but also has beneficial effects on obesity and T2DM. METHODS: A multicenter randomized controlled trial was conducted. Seventy-seven patients with obesity and T2DM were included. Thirty-eight patients were randomized to 6 months' DJBL treatment in combination with dietary intervention (34 successfully implanted, 31 completed the study), 39 patients received only dietary intervention (controls, 35 completed the study). Total study duration for both groups was 12 months, including 6 months of post-DJBL removal follow-up. RESULTS: After 6 months, just before DJBL removal, the DJBL group had lost 32.0% [22.0%-46.7%] of their excess weight versus 16.4% [4.1%-34.6%] in the control group (P < 0.05). Glycated hemoglobin A1c levels improved to 7.0% [6.4%-7.5%] in the DJBL group and to 7.9% [6.6%-8.3%] in the control group (P < 0.05). In addition, 85.3% of DJBL patients showed decreased postprandial glucose excursions versus 48.7% of control patients (P < 0.05). At 12 months, excess weight loss of the DJBL group was 19.8% [10.6%-45.0%] versus 11.7% [1.4%-25.4%] in the control group (P < 0.05). HbA1c was 7.3% [6.6%-8.0%] versus 8.0% [6.8%-8.8%], DJBL versus control respectively (P = ns). CONCLUSIONS: The DJBL is a safe and effective alternative to invasive bariatric procedures. Six months of DJBL treatment combined with diet leads to superior weight loss and improvement of T2DM when compared with diet alone.

Calorie restriction is a major determinant of the short-term metabolic effects of gastric bypass surgery in obese type 2 diabetic patients.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) and restrictive weight loss interventions, such as gastric banding (GB) and very-low-calorie diets (VLCD) directly impact glucose metabolism, possibly by calorie restriction and/or altered secretion of gut hormones. We aimed to establish the direct endocrine and metabolic effects of RYGB compared to restrictive interventions in obese glucose-tolerant (NGT) subjects and subjects with type 2 diabetes (T2DM). DESIGN: Controlled, nonrandomized observational trial. PATIENTS AND MEASUREMENTS: Four groups of obese females received a mixed meal at baseline and 3 weeks after intervention; NGT-GB (n = 11), NGT-RYGB (n = 16), T2DM-RYGB (n = 15) and T2DM-VLCD (n = 12). Normal weight controls (n = 12) were studied once. RESULTS: At baseline, all obese subjects were hyperinsulinemic. T2DM was associated with hyperglycaemia and decreased GLP-1 levels. RYGB and VLCD reduced glucose levels to a similar extent in T2DM, insulin levels decreased only after VLCD. Comparison of restrictive intervention vs RYGB showed a more pronounced decrease in glucose and insulin AUC after restriction. In NGT and T2DM subjects, RYGB increased GLP-1 and PYY levels and decreased ghrelin levels, whereas VLCD and GB only increased GIP levels. CONCLUSIONS: These data indicate that deterioration of glucose metabolism in T2DM is associated with a decline of GLP-1 levels. Calorie restriction facilitates glucose metabolism and blunts hyperinsulinemia in obese (diabetic) humans. Additional duodenal exclusion through RYGB induces gut hormone release and hyperinsulinemia but does not improve postprandial glucose levels any further. Our data thus strongly suggest that calorie restriction underlies the short-term metabolic benefits of RYGB in obese T2DM patients.

Influence of mental and behavioral factors on weight loss after bariatric surgery: A systematic review and meta-analysis.

INTRODUCTION: Multiple factors are related to lower weight loss after bariatric surgery. This review and meta-analysis evaluates the influence of several mental and behavioral factors on weight loss. METHOD: Six electronic databases were searched. Percentage excess weight loss (%EWL) was calculated for all moderator and non-moderator groups of the variables: symptoms of depression, anxiety and binge eating, compliance, physical activity, quality of life, and body image. All moderators, surgery types, and follow-up moments were analyzed separately. RESULTS: In total, 75 articles were included in the review; 12 meta-analyses were conducted. Higher postoperative compliance to follow-up was associated with 6.86%-13.68% higher EWL. Preoperative binge eating was related to more weight loss at 24- and 36-month follow-up (7.97% and 11.79%EWL, respectively). Patients with postoperative binge eating symptoms had an 11.92% lower EWL. Patients with preoperative depressive symptoms lost equal weight compared to patients without symptoms. CONCLUSION: Despite the high heterogeneity between studies, a trend emerges suggesting that the presence of postoperative binge eating symptoms and lower postoperative compliance may be associated with less weight loss after bariatric-metabolic surgery. Additionally, preoperative depressive symptoms and binge eating do not seem to significantly impact weight loss.

Evaluation of Healthcare Utilisation and Expenditures in Persons with Type 2 Diabetes Undergoing Bariatric-Metabolic Surgery.

PURPOSE: Changes in healthcare utilisation and expenditures after bariatric-metabolic surgery (BMS) for people with type 2 diabetes mellitus (T2DM) are unclear. We used the Dutch national all-payer claims database (APCD) to evaluate utilisation and expenditures in people with T2DM who underwent BMS. METHODS: In this cohort study, patients with T2DM who had BMS in 2016 were identified in the APCD. This group was matched 1:2 to a control group with T2DM who did not undergo BMS based on age, gender and healthcare expenditures. Data on healthcare expenditures and utilisation were collected for 2013-2019. RESULTS: In total, 1751 patients were included in the surgery group and 3502 in the control group. After BMS, total median expenditures in the surgery group stabilised (€ 3156 to € 3120) and increased in the control group (€ 3174 to € 3434). Total pharmaceutical expenditures decreased 28% in the surgery group (€957 to €494) and increased 55% in the control group (€605 to €936). In the surgery group, 67.1% did not use medication for T2DM in 2019 compared to 13.3% in the control group. Healthcare use for microvascular complications increased in the control group, but not in the surgery group. CONCLUSION: BMS in people with T2DM stabilises healthcare expenditures and decreases medication use and care use for microvascular complications. In contrast, healthcare use and expenditures in T2DM patients who do not undergo surgery gradually increase over time. Due to the progressive nature of T2DM, it is expected that these differences will become larger in the long-term.

Core Set of Patient-Reported Outcome Measures for Measuring Quality of Life in Clinical Obesity Care.

PURPOSE: The focus of measuring success in obesity treatment is shifting from weight loss to patients' health and quality of life. The objective of this study was to select a core set of patient-reported outcomes and patient-reported outcome measures to be used in clinical obesity care. MATERIALS AND METHODS: The Standardizing Quality of Life in Obesity Treatment III, face-to-face hybrid consensus meeting, including people living with obesity as well as healthcare providers, was held in Maastricht, the Netherlands, in 2022. It was preceded by two prior multinational consensus meetings and a systematic review. RESULTS: The meeting was attended by 27 participants, representing twelve countries from five continents. The participants included healthcare providers, such as surgeons, endocrinologists, dietitians, psychologists, researchers, and people living with obesity, most of whom were involved in patient representative networks. Three patient-reported outcome measures (patient-reported outcomes) were selected: the Impact of Weight on Quality of Life-Lite (self-esteem) measure, the BODY-Q (physical function, physical symptoms, psychological function, social function, eating behavior, and body image), and the Quality of Life for Obesity Surgery questionnaire (excess skin). No patient-reported outcome measure was selected for stigma. CONCLUSION: A core set of patient-reported outcomes and patient-reported outcome measures for measuring quality of life in clinical obesity care is established incorporating patients' and experts' opinions. This set should be used as a minimum for measuring quality of life in routine clinical practice. It is essential that individual patient-reported outcome measure scores are shared with people living with obesity in order to enhance patient engagement and shared decision-making.

How to get back on track? Experiences of patients and healthcare professionals regarding weight recurrence and needs for an intervention after bariatric-metabolic surgery.

Background: Multidisciplinary lifestyle interventions are recommended as a first step in treating weight recurrence after bariatric-metabolic surgery (BMS). However, little is known about the experience of patients and healthcare professionals (HCP) with these interventions and how they should be tailored to the patients' needs. The aim of this study was to gain more insight into the experiences and needs of patients and HCP regarding weight recurrence after BMS and an intervention to get Back on Track. In addition, attitudes towards integrating e-Health into the care program were explored. Methods: A qualitative process evaluation of an intervention for weight recurrence, the Back on Track (BoT), was conducted by means of in-depth interviews and focus groups with 19 stakeholders, including patients and HCP involved in BoT. Interviews were transcribed verbatim. Data were analyzed through thematic analysis. Results: Patients and HCP reported a wide array of causes of weight recurrence. Patients found it difficult to decide when weight recurrence is problematic and when they should ask for help. Patients reported feeling like the exception and ashamed, therefore experiencing a high threshold to seek help. E-Health was seen as a promising way to improve tailoring, screening, autonomy for the patient, and accessible contact. Conclusion: Patients should be adequately counselled on weight recurrence after BMS and the importance of intervening early. It is important to lower the threshold for seeking help. For example by offering more long-term standard care or by adding e-Health to the intervention.

Genetic variants associated with weight loss and metabolic outcomes after bariatric surgery: A systematic review.

The extent to which genetic variations contribute to interindividual differences in weight loss and metabolic outcomes after bariatric surgery is unknown. Identifying genetic variants that impact surgery outcomes may contribute to clinical decision making. This review evaluates current evidence addressing the association of genetic variants with weight loss and changes in metabolic parameters after bariatric surgery. A search was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Library. Fifty-two eligible studies were identified. Single nucleotide polymorphisms (SNPs) at ADIPOQ (rs226729, rs1501299, rs3774261, and rs17300539) showed a positive association with postoperative change in measures of glucose homeostasis and lipid profiles (n = 4), but not with weight loss after surgery (n = 6). SNPs at FTO (rs11075986, rs16952482, rs8050136, rs9939609, rs9930506, and rs16945088) (n = 10) and MC4R (rs11152213, rs476828, rs2229616, rs9947255, rs17773430, rs5282087, and rs17782313) (n = 9) were inconsistently associated with weight loss and metabolic improvement. Four studies examining the UCP2 SNP rs660339 reported associations with postsurgical weight loss. In summary, there is limited evidence supporting a role for specific genetic variants in surgical outcomes after bariatric surgery. Most studies have adopted a candidate gene approach, limiting the scope for discovery, suggesting that the absence of compelling evidence is not evidence of absence.

Changes in Fat-Free Mass, Protein Intake and Habitual Physical Activity Following Roux-en-Y Gastric Bypass Surgery: A Prospective Study.

PURPOSE: Large inter-individual variations in post-bariatric fat-free mass loss (FFML) are observed, which might relate to differences in protein intake and physical activity across patients. We performed repetitive assessments of protein intake and physical activity before and after banded Roux-en-Y gastric bypass surgery, and examined its relations to FFML during 6 months of follow-up. MATERIALS AND METHODS: FFML (bio-impedance analyses), protein intake (24-h dietary recalls) and moderate-to-vigorous physical activity (MVPA; activPAL) were assessed in 28 patients (4 males, age 42 ± 12 years) before surgery and at 1-, 3- and 6-months post-surgery. Changes in protein intake and MVPA were evaluated with mixed model analysis, whereas associations with FFML were assessed by univariate regression analysis. RESULTS: Six-month FFML was -7.3 ± 3.6 kg. Protein intake decreased from 80 ± 29 g/day (pre-surgery) to 45 ± 26 g/day (1 month post-surgery (P < 0.001)) and did not improve thereafter (51 ± 21 g/day; P > 0.05). Seven participants (25%) consumed ≥ 60 g protein/day at 6 months post-surgery. Participants performed 7394 ± 2420 steps/day in 54 ± 20 min/day of MVPA, which did not change from pre- to post-surgery (P > 0.05). A higher step count (B = -0.002; 95%CI = [-0.004 - 0.000]; P = 0.048) and higher level of MVPA (B = -0.29; 95%CI = [-0.54 - -0.03]; P = 0.018) were related to a lower FFML. CONCLUSION: A lower post-surgery FFML was attributable to higher MVPA levels but not protein intake. This may be due to the low total protein intake and the observation that only a minority of patients achieved a protein intake ≥ 60 g/day. Future studies should focus on interventions to increase post-bariatric protein intake and MVPA levels.

Early Postoperative Weight Loss Predicts Weight Loss up to 5 Years After Roux-En-Y Gastric Bypass, Banded Roux-En-Y Gastric Bypass, and Sleeve Gastrectomy.

PURPOSE: Previous studies showed that patients with lower weight loss after bariatric surgery could be identified based on early postoperative weight loss. However, these studies had only 12-36-month follow-up. This study aimed to explore whether patients in the lowest weight loss quartile at 3 months had lower weight loss trajectories up to 5 years after Roux-en-Y gastric bypass (RYGB), banded Roux-en-Y gastric bypass (BRYGB), and sleeve gastrectomy (SG) surgery. METHODS: Weight was assessed preoperatively, and 3, 6, 9, 12, 24, 36, 48, and 60 months postoperatively. Patients were grouped into four categories based on quartiles of percentage total weight loss (%TWL) at 3-month follow-up. Results were compared between the lowest %TWL quartile group and other quartile groups. RESULTS: Patients underwent either RYGB (n=13,106; 72%), SG (n=3585; 20%), or BRYGB (n=1391, 8%) surgery. Weight loss trajectories of patients in the lowest %TWL quartile group remained lower than that of other quartile groups throughout a 5-year follow-up, for all three types of surgery. Patients in the lowest %TWL quartile group had higher age at surgery, higher baseline BMI, and were more likely to be male (in the SG group), and to suffer from diabetes, hypertension, dyslipidemia, and osteoarthritis. CONCLUSION: This study showed a positive association between weight loss at 3 and 12 to 60 months after bariatric surgery. Weight loss at 3 months after surgery could be used to identify patients whose anticipated weight loss trajectories are below average, to potentially improve their outcomes through early behavioral or medical interventions.

Five-year weight loss, physical activity, and eating style trajectories after bariatric surgery.

BACKGROUND: Little research has taken individual variability in weight loss into account. Furthermore, physical activity (PA) and eating style (ES) have been linked only sporadically to weight loss longitudinally. OBJECTIVES: Identify and describe latent classes of weight loss, change of PA, and change of ES up to 5 years after surgery and investigate whether these trajectories are interrelated. SETTING: Multicenter outpatient clinic. METHODS: This is a retrospective study of data collected during standard treatment before and up to 5 years after surgery. Latent class growth analysis was used to identify trajectories of weight loss (percent total weight loss), PA (Baecke questionnaire), and ES (Dutch Eating Behavior Questionnaire). RESULTS: A total of 2785 patients were included. Follow-up rate was 84% at 1 year and 34% at 5 years. Analyses revealed 5 weight loss trajectories. Most patients followed an average, fairly stable weight loss trajectory (48%) or an above-average partial-regain trajectory (36%). Other patients followed a low-responder trajectory (9%), a rapid weight loss and weight regain trajectory (6%), or a continued weight loss trajectory (2%). Patients in the most favorable weight loss trajectory were more likely to also follow the most favorable ES trajectories. Patients following the most unfavorable weight loss trajectory were never also in the PA trajectory with an initial great increase in PA. CONCLUSION: This study distinguishes demographic and behavioral factors that may influence long-term weight loss trajectories after bariatric surgery. Trajectories varied mainly in magnitude and less in the pattern of weight loss over time, suggesting that very deviant patterns are rare.

The magnitude and progress of lean body mass, fat-free mass, and skeletal muscle mass loss following bariatric surgery: A systematic review and meta-analysis.

Postbariatric loss of muscle tissue could negatively affect long-term health due to its role in various bodily processes, such as metabolism and functional capacity. This meta-analysis aimed to unravel time-dependent changes in the magnitude and progress of lean body mass (LBM), fat-free mass (FFM), and skeletal muscle mass (SMM) loss following bariatric surgery. A systematic literature search was conducted in Pubmed, Embase, and Web of Science. Fifty-nine studies assessed LBM (n = 37), FFM (n = 20), or SMM (n = 3) preoperatively and ≥1 time points postsurgery. Random-effects meta-analyses were performed to determine pooled loss per outcome parameter and follow-up time point. At 12-month postsurgery, pooled LBM loss was -8.13 kg [95%CI -9.01; -7.26]. FFM loss and SMM loss were -8.23 kg [95%CI -10.74; -5.73] and -3.18 kg [95%CI -5.64; -0.71], respectively. About 55% of 12-month LBM loss occurred within 3-month postsurgery, followed by a more gradual decrease up to 12 months. Similar patterns were seen for FFM and SMM. In conclusion, >8 kg of LBM and FFM loss was observed within 1-year postsurgery. LBM, FFM, and SMM were predominantly lost within 3-month postsurgery, highlighting that interventions to mitigate such losses should be implemented perioperatively.