Royce P Vincent

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.

Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding

Objectives Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations. Design We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity. Results Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients. Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour.

Changes in gut hormones after bariatric surgery.

Bariatric surgery is one of the most effective treatments for achieving long‐term weight loss in morbidly obese patients. Bariatric surgery causes weight loss through substantial decline of hunger and increased satiety. Recently our understanding of neuroendocrine regulation of food intake and weight gain, especially regarding the role of gut hormones, has significantly increased. The changes in these hormones following bariatric surgery can partly explain the mechanism behind weight loss achieved through these procedures. In this paper, we review the effect bariatric procedures have on different gut hormone levels and how they in turn can alter the complex neuroendocrine regulation of energy homeostasis.

Enhanced fasting and post-prandial plasma bile acid responses after Roux-en-Y gastric bypass surgery

Abstract Objective. Exogenous bile acid (BA) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass (RYGB) surgery. Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB, with subsequent increased fasting plasma BAs. The study assessed fasting and post-prandial plasma BA response before and 15 months after RYGB. Material and methods. The prospective study recruited 63 obese individuals (43 females), aged 43 (36–56) [median (IQR)] years. Blood samples were collected before and every 30 min for 120 min after a standard 400 kcal meal. Fasting and post-prandial plasma BAs, glucagons like peptide-1 (GLP-1), –tyrosine (PYY), fasting C-reactive protein (CRP), glucose and insulin were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. Results. Following RYGB, body mass index, CRP, fasting glucose and HOMA-IR decreased; 43.7 (39.3–49.2) kg/m2 to 29.2 (25.1–35.0) kg/m2, 7.9 (4.1–11.9) mg/L to 0.4 (0.2–1.0) mg/L, 5.5 (5.0–6.0) mmol/L to 4.6 (4.3–4.9) mmol/L and 5.9 (3.5–9.2) to 1.7 (1.1–2.2), respectively, all P < 0.001. Fasting total BAs, GLP-1 and PYY increased after RYGB; 1.69 (0.70–2.56) µmol/L to 2.43 (1.23–3.82) µmol/L (P = 0.02), 6.8 (1.5–15.3) pmol/L to 17.1 (12.6–23.9) pmol/L (P < 0.001) and 4.0 (1.0–7.1) pmol/L to 15.2 (10.0–28.3) pmol/L (P < 0.001), respectively. The area under the curve for post-prandial total BAs, total glycine-conjugated BAs, GLP-1 and PYY were greater after RYGB; 486 (312–732) µmol/L/min versus 1012 (684–1921) µmol/L/min, 315 (221–466) µmol/L/min versus 686 (424–877) µmol/L/min, 3679 (3162–4537) pmol/L/min versus 5347 (4727–5781) pmol/L/min and 1887 (1423–2092) pmol/L/min versus 3296 (2534–3834) pmol/L/min, respectively, all P < 0.0001. Conclusion. Weight loss following RYGB is associated with an increase in post-prandial plasma BA response due to larger amounts of glycine-conjugated BAs. This suggests up regulation of BA production and conjugation after RYGB.

Systematic review: bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence?

Inflammatory bowel diseases (IBD), comprising Crohns disease and ulcerative colitis (UC), are chronic conditions attributed to an aberrant immune response to luminal triggers. Recently, published work suggests a pathogenic role for bile acids in this context.

Higher circulating bile acid concentrations in obese patients with type 2 diabetes.

Background Bile acids (BAs) play an important role in releasing incretin hormones via the enteroendocrine L-cell surface TGR5 receptors. The aim of this study was to investigate the difference in BA concentration at baseline and in response to a meal stimulus between type 2 diabetes mellitus (T2DM) and a matched normoglycaemic group. Materials and methods A cross-sectional study of 12 patients with known T2DM and 12 matched normoglycaemic controls compared BA fractions after an overnight fast and following a standard meal. Results The T2DM group had higher baseline glucose (P < 0.001), but baseline total BA, total glycine conjugated BAs (GCBA) and total taurine conjugated BA (TCBA) were similar between both groups. The T2DM group compared to the normoglycaemic group had a higher post-prandial peak change in total BAs 4.28 (3.51–5.38) µmol/L vs. 0.88 (0.60–1.57) µmol/L (P < 0.001) and peak total GCBA 2.77 (1.07–4.19) µmol/L vs. 0.94 (0.34–1.15) µmol/L (P < 0.0001), but similar peak total TCBA 0.36 (0.02–0.76) µmol/L vs. 0.08 (0.04–0.22) µmol/L (P=0.91). Conclusion The post-prandial bile acid response is elevated in obese patients with T2DM compared to matched normoglycaemic individuals.

Serum total cortisol and free cortisol index give different information regarding the hypothalamus–pituitary–adrenal axis reserve in patients with liver impairment

Background The short synacthen test (SST) is used to investigate patients with suspected hypothalamus–pituitary–adrenal (HPA) axis pathology. A rise of serum total cortisol (total cortisol) above 550 nmol/L is accepted as sufficient adrenal reserve. In total, 80% of cortisol is bound to cortisol-binding globulin (CBG) and 10% to albumin. In the acute phase responses CBG concentrations decrease and can influence the interpretation of SST. The free cortisol index (FCI) is a surrogate marker for free cortisol and is defined as total cortisol (nmol/L)/CBG (mg/L) with an FCI > 12 representing sufficient adrenal reserve. The aim of this study was to compare total cortisol and FCI in the interpretation of SST in patients with liver impairment. Method SST was done on 26 patients with liver impairment. Total cortisol was measured on Advia Centaur; serum CBG by radioimmunoassay and FCI calculated. Results Eleven (42%) patients had a total cortisol >550 nmol/L (range 555–2070) and FCI > 12 (12.0–68.9) suggesting sufficient cortisol reserve. Three patients (13%) had total cortisol <550 nmol/L (268–413) and FCI < 12 (3.5–11.6) consistent with cortisol deficiency. Twelve patients (46%) had a total cortisol <550 nmol/L (144–529), but an FCI > 12 (12.0–52.9). None of the patients had a total cortisol >550 nmol/L and FCI < 12. Conclusion When total cortisol alone is used to interpret SST in patients with liver impairment, 46% may have been classified as having adrenal insufficiency because of low CBG. FCI may be better for the evaluation of HPA axis insufficiency in patients with liver impairment.

High prevalence of vitamin D insufficiency in a United Kingdom urban morbidly obese population: Implications for testing and treatment

BACKGROUND Current recommendations suggest universal screening of vitamin D status before bariatric surgery to identify individuals at risk for postoperative deficiency. However little is known about the magnitude or severity of vitamin D insufficiency in the morbidly obese population awaiting bariatric surgery in the United Kingdom. The purpose of this prospective observational study was to assess the prevalence and determinants of vitamin D insufficiency in an urban multiethnic U.K. population awaiting bariatric surgery. METHODS Consecutive patients attending a morbid obesity service were comprehensively assessed using a recognized obesity staging tool. Data collected included 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), corrected calcium (Ca(2+)), body mass index (BMI), and the presence and severity of obesity associated co-morbidities, including type 2 diabetes (T2 DM), cardiovascular disease (CVD), depression, obstructive sleep apnea (OSA), and functional limitation. RESULTS Of the 118 patients assessed, 79% were female, and 21% were male, with BMI of 52.6 ± 9.4 kg/m(2) (mean ± standard deviation) and mean age of 44 ± 11 years. Twenty-four percent had T2 DM, 28% CVD, 31% OSA, and 21% depression. Vitamin D insufficiency was found in 90% of the population, with a median serum 25(OH)D of 8.8 ng/mL. Secondary hyperparathyroidism was present in 43% of those with vitamin D insufficiency. Risk was not influenced by ethnicity, age, or gender. However severe functional limitation was associated with lower vitamin D status. CONCLUSION Regardless of ethnicity, vitamin D insufficiency appears to be typical among this clinic population; therefore, routine vitamin D supplementation is suggested for all individuals awaiting bariatric surgery rather than testing vitamin D status in an attempt to identify high-risk individuals.

High density lipoprotein in patients with liver failure; relation to sepsis, adrenal function and outcome of illness

High density lipoprotein (HDL) plays an important role in the transport of cholesterol to the adrenal gland for steroidogenesis and may have actions that modulate response to infection and critical illness. The clinical relevance of HDL level in patients with liver failure remains poorly characterised.