Post-Bariatric Hypoglycemia: an Impaired Metabolic Response to a Meal.

AIMS/HYPOTHESIS: Post-bariatric hypoglycemia (PBH) is caused by postprandial hyperinsulinemia, due to anatomical alterations and changes in post-prandial metabolism after bariatric surgery. The mechanisms underlying the failing regulatory and compensatory systems are unclear. In this study, we investigated the differences in post-prandial hormones and metabolic profiles between patients with and without PBH. METHODS: We performed a mixed meal test (MMT) in 63 subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery. Blood was withdrawn at 0, 10, 20, 30, 60, and 120 min after ingestion of a standardized meal. Glucose, insulin, GLP-1, FGF-19, and FGF-21 were measured and untargeted metabolomics analysis was performed on blood plasma to analyze which hormonal and metabolic systems were altered between patients with and without PBH. RESULTS: Out of 63, a total of 21 subjects (33%) subjects developed PBH (glucose < 3.1 mmol/L) after surgery. Decreased glucose and increased insulin excursions during MMT were seen in PBH (p < 0.05). GLP-1, FGF-19, and FGF-21 were elevated after surgery (p < 0.001), but did not differ between PBH and non-PBH groups. We identified 20 metabolites possibly involved in carbohydrate metabolism which differed between the two groups, including increased carnitine and acylcholines in PBH. CONCLUSION: Overall, 33% of the subjects developed PBH 1 year after RYGB surgery. While GLP-1, FGF-19, and FGF-21 were similar in PBH and non-PBH patients, metabolomics analysis revealed changes in carnitine and acyclcholines that are possibly involved in energy metabolism, which may play a role in the occurrence of PBH.

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.

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.

Willingness for Medical Screening in a Dental Setting-A Pilot Questionnaire Study.

An important way to manage noncommunicable diseases (NCDs) is to focus on prevention, early detection, and reducing associated risk factors. Risk factors can be detected with simple general health checks, which can also be performed in dental clinics. The purpose of this study was to investigate participants' willingness to participate in general health checks at the dentist, in particular the difference in opinion between medical patients and random healthy dental attendees. A total of 100 medical patients from an outpatient internal medicine clinic and 100 dental clinic attendees were included (total of 200 participants). The participants were asked for their opinion using six closed-ended questions. Overall, 91.0% of participants were receptive to information about the risk of diabetes mellitus (DM) and cardiovascular diseases (CVD). The majority (80-90%) was receptive to screening for DM and CVD risk, such as weight and height measurements, blood pressure measurement, saliva testing for CVD and to measure glucose and cholesterol via finger stick. No significant differences were found in the frequencies of the responses between the different groups based on health status, age, sex, or cultural background. This study shows that most participants are willing to undergo medical screening at the dentist for early detection and/or prevention of common NCDs.

Attachment style and post-bariatric surgery health behaviours: the mediating role of self-esteem and health self-efficacy.

BACKGROUND: Attachment avoidance and anxiety have been linked to overweight and poor health behaviours, yet the mechanisms that underpin the relationship between attachment and health behaviours are not fully understood. Self-esteem and self-efficacy have been found to differ between attachment styles, rendering these variables potential mediators of the relationship. This longitudinal study investigated the serial mediation between preoperative attachment and 2-year post-operative health behaviours through self-esteem and health self-efficacy. METHODS: Participants were 263 bariatric surgery patients (75.7% females, aged 47.7 ± 10.4 years, BMI 38.9 ± 3.6 kg/m2) assessed before the operation and again one and two years after the surgery. Patients completed the Experiences for Close Relationships Brief Scale, Rosenberg Self-esteem scale, Weight Efficacy Lifestyle Questionnaire, Bariatric Surgery Self-Management Questionnaire, Exercise Self-Efficacy Scale and the Exercise Behaviour Scale. RESULTS: Higher preoperative attachment anxiety and avoidance were associated with lower self-esteem one year after bariatric surgery and poorer health self-efficacy two years after the surgery. Self-esteem and health self-efficacy mediated the relationships between preoperative anxious and avoidant attachment and 2- year post-operative diet adherence and physical activity. CONCLUSIONS: Helping patients to feel more worthy and reinforcing their beliefs about their own competences could lead to higher engagement with healthy lifestyle and adherence to treatment protocols, ultimately helping patients to achieve their goals for bariatric surgery. CLINICAL TRIAL REGISTRATION: BARIA: Netherlands Trial Register: NL5837 (NTR5992) https://www.trialregister.nl/trial/5837 . Diabaria: ClinicalTrials.gov identifier (NCT number): NCT03330756.

A Prospective Study on the Diagnoses for Abdominal Pain After Bariatric Surgery: The OPERATE Study.

PURPOSE: Long-term follow-up after bariatric surgery (BS) reveals high numbers of patients with abdominal pain that often remains unexplained. The aim of this prospective study was to give an overview of diagnoses for abdominal pain, percentage of unexplained complaints, number and yield of follow-up visits, and time to establish a diagnosis. MATERIALS AND METHODS: Patients who visited the Spaarne Gasthuis Hospital, The Netherlands, between December 2020 and December 2021 for abdominal pain after BS, were eligible and followed throughout the entire episode of abdominal pain. Distinction was made between presumed and definitive diagnoses. RESULTS: The study comprised 441 patients with abdominal pain; 401 (90.9%) females, 380 (87.7%) had Roux-en-Y gastric bypass, mean (SD) % total weight loss was 31.4 (10.5), and median (IQR) time after BS was 37.0 (11.0-66.0) months. Most patients had 1-5 follow-up visits. Readmissions and reoperations were present in 212 (48.1%) and 164 (37.2%) patients. At the end of the episode, 88 (20.0%) patients had a presumed diagnosis, 183 (41.5%) a definitive diagnosis, and 170 (38.5%) unexplained complaints. Most common definitive diagnoses were cholelithiasis, ulcers, internal herniations, and presumed diagnoses irritable bowel syndrome (IBS), anterior cutaneous nerve entrapment syndrome, and constipation. Median (IQR) time to presumed diagnoses, definitive diagnoses, or unexplained complaints was 16.0 (3.8-44.5), 2.0 (0.0-31.5), and 13.5 (1.0-53.8) days (p < 0.001). Patients with IBS more often had unexplained complaints (OR 95%CI: 4.457 [1.455-13.654], p = 0.009). At the end, 71 patients (16.1%) still experienced abdominal pain. CONCLUSION: Over a third of abdominal complaints after BS remains unexplained. Most common diagnoses were cholelithiasis, ulcers, and internal herniations.

Efficacy and safety of revisional treatments for weight regain or insufficient weight loss after Roux-en-Y gastric bypass: A systematic review and meta-analysis.

Weight regain or inadequate weight loss following Roux-en-Y gastric bypass poses a significant clinical challenge. Our objective was to evaluate various revisional techniques for addressing weight regain and insufficient weight loss after Roux-en-Y gastric bypass through a systematic review and meta-analysis. We performed a literature search (in PubMed and Embase) on revisional interventions in collaboration with a medical information specialist. Measured outcomes included body mass index at intervention, total weight loss during follow-up, and complications. Random effects models were used to determine pooled effect size and corresponding 95% confidence intervals. Thirty-nine studies were included: four studies reported on argon plasma coagulation, four studies on transoral outlet reduction, nine studies on transoral outlet reduction + argon plasma coagulation, four studies on pouch/gastrojejunal anastomosis revision, five on laparoscopic gastric banding, two studies on laparoscopic gastric banding + pouch resizing, 10 on distalization-RYGB, and one on duodenal switch. All techniques resulted in short-term clinically relevant weight loss. Endoscopic procedures had a short follow-up and resulted in modest and temporary weight loss. Surgical revision techniques were successful for weight loss in longer term follow-up, at the expense of high complication rates.

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.

Identifying Gut Microbiota associated with Gastrointestinal Symptoms upon Roux-en-Y Gastric Bypass.

PURPOSE: Roux-en-Y gastric bypasses (RYGB) are frequently accompanied by long-term gastrointestinal (GI) symptoms. Direct mechanistic insight into the causation of these symptoms is lacking, but changes in the intestinal microbiome have been proposed to play a role. With this study, we aimed to investigate whether a microbial predisposition exists before RYGB which is associated with GI symptoms during follow-up and to evaluate which microbial groups are involved. MATERIALS AND METHODS: In total, 67 RYGB patients were included. Shotgun metagenomic sequencing was performed on fecal samples obtained just before and 1 year after surgery. To assess GI symptoms, patients filled out Gastrointestinal Quality of Life Index (GIQLI) questionnaires and were divided into groups based on their total GIQLI score and change in score (postsurgery versus baseline). Extremely randomized tree predictor models were used to identify the most distinctive microbial species associated with postoperative GI symptoms. RESULTS: Beta diversity differed significantly between baseline and 1-year post-surgery samples, with the post-surgery microbiome resembling a more dysbiotic profile. The most predictive species regarding total GIQLI (AUC 0.77) or delta GIQLI score (AUC 0.83) were identified. Many of these species are known butyrate producers or species known to support them and/or species with anti-inflammatory properties, including Coprococcus eutactus, Faecalibacterium prausnitzii, and Ruminococcus callidus. CONCLUSION: Beneficial commensal gut microbiota related to a high GI score were associated to adequate intestinal fermentative capacity, suggesting these species might have protective properties against postoperative GI malfunctioning.

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.

Are male patients undergoing bariatric surgery less healthy than female patients?

BACKGROUND: Male patients are underrepresented in bariatric surgery (BS) despite a relatively equal proportion of men and women experiencing obesity. OBJECTIVES: Differences in frequency and severity of obesity-associated medical problems (OAMPs) between men and women undergoing BS or in a control group (HELIUS [HEalthy Life In an Urban Setting]) were evaluated. The hypothesis was that men undergoing BS are less healthy than women. SETTING: A cross-sectional study of 2 cohorts undergoing BS in 2013 (BS2013) and 2019 (BS2019) and a control group of patients with severe obesity from a general population (HELIUS). METHODS: Characteristics concerning weight and OAMPs, medication usage, intoxications, postoperative complications (for BS2019) were compared between men and women. Members of the HELIUS cohort were tested for eligibility for BS. RESULTS: Of 3244 patients included, the majority were female (>78.4%). Median (interquartile range) age and body mass index (kg/m2) in male versus female patients were 47.0 (41.0-53.8) versus 43.0 (36.0-51.0) years and 41.5 (38.4-45.2) versus 42.3 (40.2-45.9), respectively, in BS2013, and 52.0 (39.8-57.0) versus 45.0 (35.0-53.0) years and 40.4 (37.4-43.8) versus 41.3 (39.0-44.1) in BS2019 (P < .05). The rates of men with OAMPs were 71.4% and 82.0% compared with 50.2% and 56.9% of women in BS2013 and BS2019, respectively. Overall medication usage was higher in male patients (P = .014). In BS2019, male patients exhibited a higher median HbA1C (P < .001) and blood pressure (P = .003) and used more antihypertensives and antidiabetics (P = .004). Postoperative complications did not differ between men and women. In the control cohort, 66.5% of men and 66.6% of women were eligible for BS. CONCLUSION: Men undergoing BS more often experience OAMPs than women, and OAMPs are more advanced in men.

Self-organized metabotyping of obese individuals identifies clusters responding differently to bariatric surgery.

Weight loss through bariatric surgery is efficient for treatment or prevention of obesity related diseases such as type 2 diabetes and cardiovascular disease. Long term weight loss response does, however, vary among patients undergoing surgery. Thus, it is difficult to identify predictive markers while most obese individuals have one or more comorbidities. To overcome such challenges, an in-depth multiple omics analyses including fasting peripheral plasma metabolome, fecal metagenome as well as liver, jejunum, and adipose tissue transcriptome were performed for 106 individuals undergoing bariatric surgery. Machine leaning was applied to explore the metabolic differences in individuals and evaluate if metabolism-based patients' stratification is related to their weight loss responses to bariatric surgery. Using Self-Organizing Maps (SOMs) to analyze the plasma metabolome, we identified five distinct metabotypes, which were differentially enriched for KEGG pathways related to immune functions, fatty acid metabolism, protein-signaling, and obesity pathogenesis. The gut metagenome of the most heavily medicated metabotypes, treated simultaneously for multiple cardiometabolic comorbidities, was significantly enriched in Prevotella and Lactobacillus species. This unbiased stratification into SOM-defined metabotypes identified signatures for each metabolic phenotype and we found that the different metabotypes respond differently to bariatric surgery in terms of weight loss after 12 months. An integrative framework that utilizes SOMs and omics integration was developed for stratifying a heterogeneous bariatric surgery cohort. The multiple omics datasets described in this study reveal that the metabotypes are characterized by a concrete metabolic status and different responses in weight loss and adipose tissue reduction over time. Our study thus opens a path to enable patient stratification and hereby allow for improved clinical treatments.

Cost-effectiveness of ursodeoxycholic acid in preventing new-onset symptomatic gallstone disease after Roux-en-Y gastric bypass surgery.

BACKGROUND: The aim was to evaluate the cost-effectiveness and cost-utility of ursodeoxycholic acid (UDCA) prophylaxis for the prevention of symptomatic gallstone disease after Roux-en-Y gastric bypass (RYGB) in patients without gallstones before surgery. METHODS: Data from a multicentre, double-blind, randomized placebo-controlled superiority trial were used. Patients scheduled for laparoscopic RYGB or sleeve gastrectomy were randomized to receive 900 mg UDCA or placebo for 6 months. Indicated by the clinical report, prophylactic prescription of UDCA was evaluated economically against placebo from a healthcare and societal perspective for the subgroup of patients without gallstones before surgery who underwent RYGB. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses, and productivity loss were assessed. Main outcomes were the costs per patient free from symptomatic gallstone disease and the costs per quality-adjusted life-year (QALY). RESULTS: Patients receiving UDCA prophylaxis were more likely to remain free from symptomatic gallstone disease (relative risk 1.06, 95 per cent c.i. 1.02 to 1.11; P = 0.002) compared with patients in the placebo group. The gain in QALYs, corrected for a baseline difference in health utility, was 0.047 (95 per cent bias-corrected and accelerated (Bca) c.i. 0.007 to 0.088) higher (P = 0.022). Differences in costs were -€356 (95 per cent Bca c.i. €-1573 to 761) from a healthcare perspective and -€1392 (-3807 to 917) from a societal perspective including out-of-pocket expenses and productivity loss, both statistically non-significant, in favour of UDCA prophylaxis. The probability of UDCA prophylaxis being cost-effective was at least 0.872. CONCLUSION: UDCA prophylaxis after RYGB in patients without gallstones before surgery was cost-effective.

A systems biology approach to study non-alcoholic fatty liver (NAFL) in women with obesity.

Non-alcoholic fatty liver disease (NAFLD) is now the most frequent global chronic liver disease. Individuals with NAFLD exhibited an increased risk of all-cause mortality driven by extrahepatic cancers and liver and cardiovascular disease. Once the disease is established, women have a higher risk of disease progression and worse outcome. It is therefore critical to deepen the current knowledge on the pathophysiology of NAFLD in women. Here, we used a systems biology approach to investigate the contribution of different organs to this disease. We analyzed transcriptomics profiles of liver and adipose tissues, fecal metagenomes, and plasma metabolomes of 55 women with and without NAFLD. We observed differences in metabolites, expression of human genes, and gut microbial features between the groups and revealed that there is substantial crosstalk between these different omics sets. Multi-omics analysis of individuals with NAFLD may provide novel strategies to study the pathophysiology of NAFLD in humans.

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.

Factors associated with adherence to ursodeoxycholic acid or placebo in patients after bariatric surgery.

BACKGROUND: Ursodeoxycholic acid (UDCA) reduces symptomatic gallstone disease after Roux-en-Y gastric bypass (RYGB). The beneficial effect of UDCA is reduced by poor adherence. OBJECTIVES: We aimed to identify factors associated with poor adherence to UDCA or placebo after bariatric surgery. SETTING: Outpatient clinic and department for bariatric surgery in three hospitals in the Netherlands. METHODS: Patients in the multicenter, double-blind, randomized, placebo-controlled UPGRADE trial were assessed for adherence to 900 mg UDCA or placebo for 6 months through a pill count, inquiries during follow-up, and a questionnaire. Poor adherence was defined as the usage of <300 of 364 pills within a maximum of 8 months postoperatively. Multivariable logistic regression analysis was used to identify factors contributing to poor adherence. RESULTS: In total, 967 patients were included (mean age [standard deviation (SD)]: 45.1 [11.1] years; female: 772 [80%]; RYGB: 889 [92%]; sleeve gastrectomy: 78 [8%]), of whom 357 (37%) were poor adherers. Factors associated with poor adherence were age (OR .97; 95% confidence interval [CI] .96-.98, a decrease in age increases the odds for poor adherence), foreign origin (odds ratio [OR] 2.07; 95%CI 1.50-2.84), unemployment (OR 1.73; 95%CI 1.28-2.34), and sleeve gastrectomy (OR 1.79; 95%CI 1.06-3.01). Furthermore, a difference in adherence status was also noted for the centers of surgery. CONCLUSIONS: The adherence rate to UDCA and placebo in the UPGRADE trial was suboptimal. Several factors were independently associated with poor adherence. Our findings can help to identify patients who may benefit from extra guidance to improve adherence.

Risk Factors for Symptomatic Gallstone Disease and Gallstone Formation After Bariatric Surgery.

PURPOSE: Patients who undergo bariatric surgery are at risk for developing cholesterol gallstones. We aimed to identify risk factors that are associated with symptomatic gallstone disease and gallstone formation after bariatric surgery. MATERIALS AND METHODS: We included participants of the UPGRADE trial, a multicenter randomized placebo-controlled trial on the prevention of symptomatic gallstone disease with ursodeoxycholic acid (UDCA) after bariatric surgery. The association between patient characteristics and symptomatic gallstone disease, and gallstone formation was evaluated using logistic regression analysis. RESULTS: Of 959 patients, 78 (8%) developed symptomatic gallstone disease within 24 months. Risk factors were the presence of a pain syndrome (OR 2.07; 95% CI 1.03 to 4.17) and asymptomatic gallstones before surgery (OR 3.15; 95% CI 1.87 to 5.33). Advanced age (OR 0.95; 95% CI 0.93 to 0.97) was protective, and UDCA prophylaxis did not reach statistical significance (OR 0.64; 95% CI 0.39 to 1.03). No risk factors were identified for gallstone formation, whereas advanced age (OR 0.98; 95% CI 0.96 to 1.00), statin use (OR 0.42; 95% CI 0.20 to 0.90), and UDCA prophylaxis (OR 0.47; 95% CI 0.30 to 0.73) all reduced the risk. CONCLUSION: Young patients with a preoperative pain syndrome and/or asymptomatic gallstones before bariatric surgery are at increased risk for symptomatic gallstone disease after surgery. Whether statins, either alone or in combination with UDCA prophylaxis, can further reduce the burden of gallstones after bariatric surgery should be investigated prospectively.

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.

Pancreatic exocrine insufficiency after bariatric surgery.

BACKGROUND: Chronic abdominal complaints after bariatric surgery may be explained by pancreatic exocrine insufficiency (PEI). OBJECTIVES: We aimed to evaluate the clinical value of the Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) as a screening tool to identify patients with a high probability of having PEI. SETTING: Outpatient clinic for bariatric surgery. METHODS: Patients scheduled for a screening or follow-up appointment were asked to complete the PEI-Q and the Gastrointestinal Quality of Life Index questionnaire (GIQLI). Postoperative patients with a high PEI-Q score (0,6) were offered a fecalelastase (FE) test (abnormal if <200 µg/g). RESULTS: Between June 2020 and February 2021, a total of 1600 of 1629 PEI-Qs were completed, 1073 (67%) of which after surgery. The postoperative group consisted mostly of females (81.9%), aged 49.0 ± 10.6 years, with a total weight loss of 30.3% ± 8.8%. Among them, 63.4% had abnormal PEI-Q scores compared with 34.9% before surgery (P < .01). In contrast, the median GIQLI score increased (119 [interquartile range (IQR), 107-129.25] versus 110 [IQR, 95-121.75]) before surgery (P < .01). Additionally, 310 FE tests were performed, of which only 11.9% was suggestive of PEI. No correlation was found between the PEI-Q scores and FE levels (c-index .55). CONCLUSION: The PEI-Q in its current version is not able to distinguish complaints of PEI and bariatric surgery itself and therefore cannot be used as a screening tool for PEI. The specificity of the FE test seems to be reduced after surgery. Future research should include a more direct pancreatic function test, which may provide more insight into PEI after bariatric surgery.