David Mahon

The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control

Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes.

Remission of Type 2 Diabetes After Gastric Bypass and Banding: Mechanisms and 2 Year Outcomes

Objective: To investigate the rate of type 2 diabetes remission after gastric bypass and banding and establish the mechanism leading to remission of type 2 diabetes after bariatric surgery. Summary Background Data: Glycemic control in type 2 diabetic patients is improved after bariatric surgery. Methods: In study 1, 34 obese type 2 diabetic patients undergoing either gastric bypass or gastric banding were followed up for 36 months. Remission of diabetes was defined as patients not requiring hypoglycemic medication, fasting glucose below 7 mmol/L, 2 hour glucose after oral glucose tolerance test below 11.1 mmol/L, and glycated haemoglobin (HbA1c) <6%. In study 2, 41 obese type 2 diabetic patients undergoing either bypass, banding, or very low calorie diet were followed up for 42 days. Insulin resistance (HOMA-IR), insulin production, and glucagon-like peptide 1 (GLP-1) responses after a standard meal were measured. Results: In study 1, HbA1c as a marker of glycemic control improved by 2.9% after gastric bypass and 1.9% after gastric banding at latest follow-up (P < 0.001 for both groups). Despite similar weight loss, 72% (16/22) of bypass and 17% (2/12) of banding patients (P = 0.001) fulfilled the definition of remission at latest follow-up. In study 2, within days, only bypass patients had improved insulin resistance, insulin production, and GLP-1 responses (all P < 0.05). Conclusions: With gastric bypass, type 2 diabetes can be improved and even rapidly put into a state of remission irrespective of weight loss. Improved insulin resistance within the first week after surgery remains unexplained, but increased insulin production in the first week after surgery may be explained by the enhanced postprandial GLP-1 responses.

Effect of the definition of type II diabetes remission in the evaluation of bariatric surgery for metabolic disorders.

The American Diabetes Association recently defined remission of type II diabetes as a return to normal measures of glucose metabolism (haemoglobin (Hb) A1c below 6 per cent, fasting glucose less than 5·6 mmol/l) at least 1 year after bariatric surgery without hypoglycaemic medication. A previously used common definition was: being off diabetes medication with normal fasting blood glucose level or HbA1c below 6 per cent. This study evaluated the proportion of patients achieving complete remission of type II diabetes following bariatric surgery according to these definitions.

Postprandial plasma bile acid responses in normal weight and obese subjects

Background Bile acids can act as signalling molecules via various receptors including the nuclear farnesoid X receptor (FXR) and pregnane X receptor (PXR), and the cell surface G-protein-coupled receptor TGR5. The signalling has been implicated in the release of peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), which improves glycaemic control and energy expenditure. We investigated whether morbidly obese subjects have altered postprandial bile acid responses in comparison to normal weight subjects. Method Blood samples were taken every 30 min from 0 to 180 min following a 400 kcal test meal. Samples were taken from 12 normal weight subjects with a body mass index (BMI) of 23.2 (2.8) kg/m2 (median [interquartile range (IQR)]) and seven obese patients with a BMI of 47.2 (7.2) kg/m2. Fractionated bile acids were measured on these samples using high-performance liquid chromatography tandem mass spectrometry. Results The obese subjects showed a lower postprandial response in total bile acids compared with the normal weight subjects. An increase of 6.4 (5.0) and 2.6 (3.3) μmol/L (median [IQR]) in normal weight and obese subjects was observed, respectively (P = 0.02). The difference was predominantly due to the glycine-conjugated fraction (P = 0.03). There was no difference in the increase of the unconjugated or taurine-conjugated fractions. Conclusions The decreased postprandial bile acid response in obese subjects compared with normal weight subjects may partly explain the suboptimal GLP-1 and PYY responses and could affect appetite, glycaemic control and energy expenditure.

Outcome reporting in bariatric surgery: An in-depth analysis to inform the development of a core outcome set, the BARIACT Study

Outcome reporting in bariatric surgery needs a core outcome set (COS), an agreed minimum set of outcomes reported in all studies of a particular condition. The aim of this study was to summarize outcome reporting in bariatric surgery to inform the development of a COS. Outcomes reported in randomized controlled trials (RCTs) and large non‐randomized studies identified by a systematic review were listed verbatim and categorized into domains, scrutinizing the frequency of outcome reporting and uniformity of definitions. Ninety studies (39 RCTs) identified 1,088 separate outcomes, grouped into nine domains with most (n = 920, 85%) reported only once. The largest outcome domain was ‘surgical complications’, and overall, 42% of outcomes corresponded to a theme of ‘adverse events’. Only a quarter of outcomes were defined, and where provided definitions, which were often contradictory. Percentage of excess weight loss was the main study outcome in 49 studies, but nearly 40% of weight loss outcomes were heterogeneous, thus not comparable. Outcomes of diverse bariatric operations focus largely on adverse events. Reporting is inconsistent and ill‐defined, limiting interpretation and comparison of published studies. Thus, we propose and are developing a COS for the surgical treatment of severe and complex obesity.

Polycystic ovary syndrome is common in patients undergoing bariatric surgery in a British center

We read with great interest the article by Gosman et al. (1). The authors highlight that 13.1% of female patients undergoing bariatric surgery already had had polycystic ovary syndrome (PCOS) diagnosed by a health care provider. Data on the incidence of PCOS in this population from outside the United States and the United Kingdom in particular are limited. Our group has recently measured prospectively the prevalence of PCOS in 149 consecutive women of childbearing age (18–45 years old) undergoing bariatric surgery using the same question as the one used by Gosman et al. (1), that is, ‘‘Have you ever been told by a health care provider that you have PCOS?’’ Twenty-three of 149 (15.4%) women replied yes. The mean age ( SD) was 32.1 ( 6.6) years, and the mean body mass index was 50.7 ( 5.2). The prevalence of PCOS in our United Kingdom sample was higher than reported in the general population (2, 3).

Acute Giant Gastric Volvulus Causing Cardiac Tamponade

IntroductionAcute gastric volvulus is an uncommon condition which is rarely associated with cardiac impairment.DiscussionWe report a patient with an acute giant gastric volvulus causing cardiac tamponade. Prompt decompression was unsuccessful and the patient died prior to definitive treatment.

Enabling recruitment success in bariatric surgical trials: Pilot phase of the By-Band-Sleeve study

Background:Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a qualitative research integrated in trials (QuinteT) recruitment intervention (QRI).Patients/Methods:The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization.Results:Recruitment proved to be extremely difficult with only two patients recruited during the first 2 months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first 2 months (2/22) to 40% (26/65) in the 4 months thereafter. Center B, commencing recruitment 3 months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers.Conclusions:The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial—currently the largest in bariatric practice—and offers opportunities to optimize recruitment in other trials in bariatrics.

Influence of social deprivation on provision of bariatric surgery: 10-year comparative ecological study between two UK specialist centres

Objective To investigate the effect of residential location and socioeconomic deprivation on the provision of bariatric surgery. Design Retrospective cross-sectional ecological study. Setting Patients resident local to one of two specialist bariatric units, in different regions of the UK, who received obesity surgery between 2003 and 2013. Methods Demographic data were collected from prospectively collected databases. Index of Multiple Deprivation (IMD 2010) was used as a measure of socioeconomic status. Obesity prevalences were obtained from Public Health England (2006). Patients were split into three IMD tertiles (high, median, low) and also tertiles of time. A generalised linear model was generated for each time period to investigate the effect of socioeconomic deprivation on the relationship between bariatric case count and prevalence of obesity. We used these to estimate surgical intervention provided in each population in each period at differing levels of deprivation. Results Data were included from 1163 bariatric cases (centre 1–414, centre 2–749). Incidence rate ratios (IRRs) were calculated to measure the associations between predictor and response variables. Associations were highly non-linear and changed over the 10-year study period. In general, the relationship between surgical case volume and obesity prevalence has weakened over time, with high volumes becoming less associated with prevalence of obesity. Discussion As bariatric services have matured, the associations between demand and supply factors have changed. Socioeconomic deprivation is not apparently a barrier to service provision more recently, but the positive relationships between obesity and surgical volume we would expect to find are absent. This suggests that interventions are not being taken up in the areas of need. We recommend a more detailed national analysis of the relationship between supply side and demand side factors in the provision of bariatric surgery.

Outcome reporting in bariatric surgery: an in-depth analysis to inform the development of a core outcome set, the BARIACT Study: Bariact Study core outcome set

Outcome reporting in bariatric surgery needs a core outcome set (COS), an agreed minimum set of outcomes reported in all studies of a particular condition. The aim of this study was to summarize outcome reporting in bariatric surgery to inform the development of a COS. Outcomes reported in randomized controlled trials (RCTs) and large non‐randomized studies identified by a systematic review were listed verbatim and categorized into domains, scrutinizing the frequency of outcome reporting and uniformity of definitions. Ninety studies (39 RCTs) identified 1,088 separate outcomes, grouped into nine domains with most (n = 920, 85%) reported only once. The largest outcome domain was ‘surgical complications’, and overall, 42% of outcomes corresponded to a theme of ‘adverse events’. Only a quarter of outcomes were defined, and where provided definitions, which were often contradictory. Percentage of excess weight loss was the main study outcome in 49 studies, but nearly 40% of weight loss outcomes were heterogeneous, thus not comparable. Outcomes of diverse bariatric operations focus largely on adverse events. Reporting is inconsistent and ill‐defined, limiting interpretation and comparison of published studies. Thus, we propose and are developing a COS for the surgical treatment of severe and complex obesity.