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.

Genetic glucocorticoid receptor variants differ between ethnic groups but do not explain variation in age of diabetes onset, metabolic and inflammation parameters in patients with type 2 diabetes.

Aims: The effect of excess glucocorticoid receptor (GR) stimulation through glucocorticoid medication or cortisol on glucose metabolism is well established. There are genetic GR variants that result in increased or decreased GR stimulation. We aimed to determine the prevalence of genetic GR variants in different ethnic groups in a cohort of patients with type 2 diabetes, and we aimed to determine their association with age of diabetes onset and metabolic and inflammation parameters. Methods: A cross-sectional analysis was performed in a multiethnic cohort (n = 602) of patients with established type 2 diabetes. Polymorphisms in the GR gene that have previously been associated with altered glucocorticoid sensitivity (TthIIII, ER22/23EK N363S, BclI and 9ß) were determined and combined into 6 haplotypes. Associations with age of diabetes onset, HbA1c, hs-CRP and lipid values were evaluated in multivariate regression models. Results: The prevalence of the SNPs of N363S and BclI was higher in Dutch than in non-Dutch patients. We observed a lower prevalence of the SNP 9ß in Dutch, South(East) Asian and Black African patients versus Turkish and Moroccan patients. We did not detect an association between SNPs and diabetes age of onset or metabolic parameters. We only found a trend for lower age of onset and higher HbA1c in patients with 1 or 2 copies of haplotype 3 (TthIIII + 9ß). Conclusions: The prevalence of genetic GR variants differs between patients of different ethnic origins. We did not find a clear association between genetic GR variants and age of diabetes onset or metabolic and inflammation parameters. This indicates that the clinical relevance of GR variants in patients with established type 2 diabetes is limited.

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.

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.

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.

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.

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.

Medical and surgical treatment of postbariatric hypoglycaemia: Retrospective data from daily practice.

AIM: To evaluate medical and surgical treatment of postbariatric hypoglycaemia (PBH) in daily practice. MATERIALS AND METHODS: Retrospective data were extracted from medical records from four hospitals. PBH was defined by neuroglycopenic symptoms together with a documented glucose <3.0 mmol/L in the postprandial setting after previous bariatric surgery. Data were scored semiquantitatively on efficacy and side effects by two reviewers independently. Duration of efficacy and of use were calculated. RESULTS: In total, 120 patients were included with a median follow-up of 27 months with a mean baseline age of 41 years, total weight loss of 33% and glucose nadir 2.3 mmol/L. Pharmacotherapy consisted of acarbose, diazoxide, short- and long-acting octreotide and glucagon-like peptide-1 receptor agonist analogues (liraglutide and semaglutide) with an overall efficacy in 45%-75% of patients. Combination therapy with two drugs was used by 30 (25%) patients. The addition of a second drug was successful in over half of the patients. Long-acting octreotide and the glucagon-like peptide-1 receptor agonist analogues scored best in terms of efficacy and side effects with a median duration of use of 35 months for octreotide. Finally, 23 (19%) patients were referred for surgical intervention. Efficacy of the surgical procedures, pouch banding, G-tube placement in remnant stomach and Roux-en-Y gastric bypass reversal, pooled together, was 79% with a median duration of initial effect of 13 months. CONCLUSIONS: In daily practice, pharmacotherapy for PBH was successful in half to three quarters of patients. Combination therapy was often of value. One in five patients finally needed a surgical procedure, with overall good results.

An examination of the risk of periodontitis for nonfatal cardiovascular diseases on the basis of a large insurance claims database.

OBJECTIVES: Although many studies have reported a higher risk of atherosclerotic cardiovascular diseases (ACVD) in people with periodontitis (PD), this has been tested in a few large-scale population-based studies with a longitudinal design. The aim of this study was to investigate whether people with PD status have an increased risk of a nonfatal ACVD event compared to people without PD status. METHODS: A cohort of 1.2 million participants from a healthcare insurance claims database was studied longitudinally for a period of 8 years. PD status was derived from PD-related insurance claims and ACVD status from ACVD-related insurance claims. Person-time at risk (PTAR) was calculated from the start of follow-up (01 January 2007) for participants with and without PD status until ACVD or event-free censoring (31 December 2014). Time-dependent Cox proportional hazard models were used to calculate the hazard ratio (HR) and to adjust for shared risk factors (age, sex, socioeconomic position and diabetes mellitus). RESULTS: The prevalence of PD was 20.1%, and the cumulative incidence of nonfatal ACVD events was 7.5%. The univariable and multivariable analyses revealed a limited risk of ACVD for participants with PD status (HR: 1.12; 95% CI 1.10-1.14, HR: 1.06; 95% CI 1.04-1.08, respectively). A subgroup analysis of participants ≤35 and > 35 years of age showed that those ≤35 years of age with PD status had a higher ACVD risk (univariable HR: 1.20; 95% CI 1.05-1.37, multivariable HR: 1.21; 95% CI 1.05-1.39). ACVD risk was not increased in participants >35 years of age with PD status (univariable HR: 0.92; 95% CI 0.91-0.94, multivariable HR: 0.96; 95% CI 0.94-0.98). CONCLUSIONS: This study based on a healthcare insurance cohort shows that PD can hardly be regarded as a risk factor for nonfatal ACVD. The increased risk is of minor size, and therefore, the proposed role of PD in the development of ACVD events should be reconsidered. Possibly PD plays a role as a risk factor in younger people due to overlapping genetic risk factors of ACVD and a more aggressive course of PD.

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.

Microbiome-derived ethanol in nonalcoholic fatty liver disease.

To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17-516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman's rho, 0.42; P < 10-5) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.

Prevalence of Periodontal Disease among Patients at the Outpatient Clinic of Internal Medicine in an Academic Hospital in The Netherlands: A Cross-Sectional Pilot Study.

There is a worldwide increase in individuals suffering ≥2 chronic diseases (multimorbidity), and the cause of combinations of conditions remains largely unclear. This pilot study analysed the prevalence of periodontal disease (PD) among (multi)-morbid patients at the outpatient clinic of internal medicine. PD is an inflammatory disease of the tooth supporting tissues and has a negative impact on the overall health. Data were obtained from 345 patients, on demographics, systemic conditions and presence of PD. The possible differences in the distribution of PD status among patients with/without multimorbidity and Medical Subject Headings (MeSH) disease chapters were explored. In total, 180 (52.2%) patients suffered from multimorbidity. The prevalence of severe PD was 16.2%, while the prevalence of mild and severe PD combined (Total PD) was 53.6%. Patients with disease chapter cardiovascular diseases (CVD) had a significantly higher prevalence of severe PD (odds ratio (OR) 2.33; 95% confidence interval (CI) 1.25, 4.33) and Total PD (OR 1.61; 95% CI 1.04, 2.50) than patients without CVD. After subsequent analyses, myocardial infarction was significantly associated with severe PD (OR: 4.68 (95% CI; 1.27 to 17.25)). Those suffering from multimorbidity showed to have a non-significant increased risk for severe (OR 1.27; 95% CI 0.69, 2.34) or Total PD (OR 1.23; 95% CI 0.81, 1.88). In conclusion, PD is highly prevalent in multimorbidity patients. Furthermore, PD was significantly prevalent in patients with CVD. However, larger epidemiological studies are necessary to confirm that the prevalence of PD is significantly increased among multimorbid patients.

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.

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.