Tamara L. Debreceni

Rapid gastric and intestinal transit is a major determinant of changes in blood glucose, intestinal hormones, glucose absorption and postprandial symptoms after gastric bypass

To evaluate the effect of modulating pouch emptying (PE) and SI transit of glucose after Roux‐en‐Y gastric bypass (RYGB) on blood glucose, incretin hormones, glucose absorption and gastrointestinal (GI) symptoms.

Accelerated Intestinal Glucose Absorption in Morbidly Obese Humans: Relationship to Glucose Transporters, Incretin Hormones, and Glycemia

CONTEXT Intestinal glucose absorption is mediated by sodium-dependent glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT2), which are linked to sweet taste receptor (STR) signaling and incretin responses. OBJECTIVE This study aimed to examine intestinal glucose absorption in morbidly obese humans and its relationship to the expression of STR and glucose transporters, glycemia, and incretin responses. DESIGN/SETTING/PARTICIPANTS Seventeen nondiabetic, morbidly obese subjects (body mass index [BMI], 48 ± 4 kg/m(2)) and 11 lean controls (BMI, 25 ± 1 kg/m(2)) underwent endoscopic duodenal biopsies before and after a 30-minute intraduodenal glucose infusion (30 g glucose and 3 g 3-O-methylglucose [3-OMG]). MAIN OUTCOME MEASURES Blood glucose and plasma concentrations of 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), insulin, and glucagon were measured over 270 minutes. Expression of duodenal SGLT-1, GLUT2, and STR (T1R2) was quantified by PCR. RESULTS The increase in plasma 3-OMG (P < .001) and blood glucose (P < .0001) were greater in obese than lean subjects. Plasma 3-OMG correlated directly with blood glucose (r = 0.78, P < .01). In response to intraduodenal glucose, plasma GIP (P < .001), glucagon (P < .001), and insulin (P < .001) were higher, but GLP-1 (P < .001) was less in the obese compared with lean. Expression of SGLT-1 (P = .035), but not GLUT2 or T1R2, was higher in the obese, and related to peak plasma 3-OMG (r = 0.60, P = .01), GIP (r = 0.67, P = .003), and insulin (r = 0.58, P = .02). CONCLUSIONS In morbid obesity, proximal intestine glucose absorption is accelerated and related to increased SGLT-1 expression, leading to an incretin-glucagon profile promoting hyperinsulinemia and hyperglycemia. These findings are consistent with the concept that accelerated glucose absorption in the proximal gut underlies the foregut theory of obesity and type 2 diabetes.

Upregulation of intestinal glucose transporters after Roux-en-Y gastric bypass to prevent carbohydrate malabsorption

To determine the effect of Roux‐en‐Y gastric bypass (RYGB) on the expression of intestinal sweet taste receptors (STRs), glucose transporters (GTs), glucose absorption, and glycemia.

Outcomes of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding

AIM To evaluate weight loss and surgical outcomes of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric band (LAGB). METHODS Data relating to changes in body mass index (BMI) and procedural complications after RYGB (1995-2009; n = 609; 116M: 493F; 42.4 ± 0.4 years) or LAGB (2004-2009; n = 686; 131M: 555F; 37.2 ± 0.4 years) were extracted from prospective databases. RESULTS Pre-operative BMI was higher in RYGB than LAGB patients (46.8 ± 7.1 kg/m² vs 40.4 ± 4.2 kg/m², P < 001); more patients with BMI < 35 kg/m² underwent LAGB than RYGB (17.1% vs 4.1%, P < 0.0001). BMI decrease was greater after RYGB. There were direct relationships between weight loss and pre-operative BMI (P < 0.001). Although there was no difference in weight loss between genders during the first 3-year post-surgery, male LAGB patients had greater BMI reduction than females (-8.2 ± 4.3 kg/m² vs -3.9 ± 1.9 kg/m², P = 0.02). Peri-operative complications occurred more frequently following RYGB than LAGB (8.0% vs 0.5%, P < 0.001); majority related to wound infection. LAGB had more long-term complications requiring corrective procedures than RYGB (8.9% vs 2.1%, P < 0.001). Conversion to RYGB resulted in greater BMI reduction (-9.5 ± 3.8 kg/m²) compared to removal and replacement of the band (-6.0 ± 3.0 kg/m²). Twelve months post-surgery, fasting glucose, total cholesterol and low density lipoprotein levels were significantly lower with the magnitude of reduction greater in RYGB patients. CONCLUSION RYGB produces substantially greater weight loss than LAGB. Whilst peri-operative complications are greater after RYGB, long-term complication rate is higher following LAGB.

Patient-controlled analgesia with inhaled methoxyflurane versus conventional endoscopist-provided sedation for colonoscopy: a randomized multicenter trial

OBJECTIVE Inhaled methoxyflurane (Penthrox, Medical Device International, Melbourne, Australia) has been used extensively in Australasia (Australia and New Zealand) to manage trauma-related pain. The aim is to evaluate the efficacy, safety, and outcome of Penthrox for colonoscopy. DESIGN Prospective randomized study. SETTING Three tertiary endoscopic centers. PATIENTS Two hundred fifty-one patients were randomized to receive either Penthrox (n = 125, 70 men, 51.4 ± 1.1 years old) or intravenous midazolam and fentanyl (M&F; n = 126, 72 men, 54.9 ± 1.1 years old) during colonoscopy. MAIN OUTCOME MEASUREMENT Discomfort (visual analogue scale [VAS] pain score), anxiety (State-Trait Anxiety Inventory Form Y [STAI-Y] anxiety score), colonoscopy performance, adverse events, and recovery time. RESULTS Precolonoscopy VAS pain and STAI-Y scores were comparable between the 2 groups. There were no differences between groups in (1) pain VAS or STAI Y-1 anxiety scores during or immediately after colonoscopy, (2) procedural success rate (Penthrox: 121/125 vs M&F: 124/126), (3) hypotension during colonoscopy (7/125 vs 8/126), (4) tachycardia (5/125 vs 3/126), (5) cecal arrival time (8 ± 1 vs 8 ± 1 minutes), or (6) polyp detection rate (30/125 vs 43/126). Additional intravenous sedation was required in 10 patients (8%) who received Penthrox. Patients receiving Penthrox alone had no desaturation (oxygen saturation [SaO(2)] < 90%) events (0/115 vs 5/126; P = .03), awoke quicker (3 ± 0 vs 19 ± 1 minutes; P < .001) and were ready for discharge earlier (37 ± 1 vs 66 ± 2 minutes; P < .001) than those receiving intravenous M&F. LIMITATIONS Inhaled Penthrox is not yet available in the United States and Europe. CONCLUSIONS Patient-controlled analgesia with inhaled Penthrox is feasible and as effective as conventional sedation for colonoscopy with shorter recovery time, is not associated with respiratory depression, and does not influence the procedural success and polyp detection.

Su2015 Effects of Posture and Meal Volume on Pouch Emptying, Intestinal Transit, Blood Glucose, Gut Hormone Concentrations and Gastrointestinal Symptoms in Patients With Gastric Bypass

G A A b st ra ct s plasma leptin (p<0.01) and a decrease in NPW levels in the HFD fed mice (p<0.001). Conclusion: These results indicate a dynamic homologous and heterologous regulation in the way appetite modulatory peptides regulate satiety receptor levels and this is changed by a chronic high fat diet potentially exacerbating weight gain or making weight loss harder to achieve. Supported by University of Adelaide and NHMRC (#565186) Australia

Tu2012 Impact of a 2-Week Very Low Calorie Diet (VLCD) on Glucose Sensing, Absorption, Transporters, Incretin Hormones and Glycemia in Morbidly Obese Humans

We showed that glucose absorption is accelerated in the proximal intestine of morbidly obese humans, associated with increased expression of sodium dependent glucose co-transporter 1 (SGLT1), an altered incretin profile, hyperinsulinemia and hyperglycemia. This study aimed to examine the effects of energy restriction on glucose absorption, expression of intestinal glucose transporters and sweet taste receptors (STR), incretin hormone responses and glycemia in the morbidly obese. Methods: 10 non-diabetic, morbidly obese subjects (2M:8F; 45±3yrs, BMI: 46±3kg/m2) were studied before and after a 2-week VLCD (750kcal/day). On each occasion, endoscopic duodenal biopsies were collected before and after intraduodenal glucose infusion (30g glucose over 30 min, with 3g 3-O-methylglucose (3-OMG) to estimate glucose absorption). Blood glucose and plasma concentrations of 3-OMG, glucosedependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and insulin were measured over 240 min. Absolute expression of SGLT-1, GLUT2 and STR (T1R2) transcripts was quantified by PCR. Results After 2 weeks of VLCD, body weight (-5.6±0.5kg, P<0.001), HbA1c (-0.32±0.08%, P=0.001), fasting blood glucose (-0.5±0.1mmol/L, P=0.02) and fasting expression of T1R2 (-54±22%, P=0.03), SGLT1 (-30±7%, P=0.004) and GLUT2 (-50±15%, P=0.008) were lower than at baseline. Prior to VLCD, intra-duodenal glucose had no impact onT1R2, SGLT-1 and GLUT2 expression, but after VLCD, intra-duodenal glucose stimulated increased expression of T1R2 (45±30%, P=0.03) and GLUT2 (57±14%, P=0.003). The blood glucose (P=0.002), plasma GIP (P=0.03) and plasma insulin (P=0.002) responses to intra-duodenal glucose were all reduced after VLCD, while plasma 3-OMG and GLP-1 concentrations were unchanged. CONCLUSIONS: The improvement in glycemic control after short-term VLCD in morbid obesity is most likely mediated by reduced insulin resistance from weight loss, but not via a reduction in intestinal glucose absorption or an increased incretin response. Although VCLD reduces the fasting expression of both STR and glucose transporters, these increase rapidly on exposure to glucose. Further studies with inhibitors of STR and/or glucose transporters are warranted to determine whether the changes in receptor expressional dynamics are responsible for the observed incretin responses.

483 Delayed Gastric Emptying Is Common in Liver Cirrhosis and Is Associated With Reduced Appetite and Glucose Absorption: A Risk Factor for Malnutrition?

A S L D A b st ra ct s score / year; p=0.42) and NAS score (1.71 vs 1.88 score / year; p=0.88) were higher among NASH recipients without significance while fibrosis score was significantly higher (0.43 vs 1 stage / year; p=0.0045) in ALD recipients. The incremental increase in the rate of fibrosis was faster in the first year compared to 4-5 years (0.8 vs 0.04 stage / year) following LT. This decreased in the rate of fibrosis progression at 4-5 years was significant among NASH recipients compared to ALD recipients (0.04 vs 0.33 stage /year; p=0.015) [Figure 1]. No single factor was associated with rate of fibrosis progression among NASH patients on multivariate analysis. Conclusion: NASH recurs following LT. The rate of fibrosis progression is slower among NASH recipients compared to ALD recipients despite increased steatosis and NASH features. This fibrosis progression is reduced in the subsequent years of LT nearing the pre-transplant rate of fibrosis progression with favorable outcome in NASH patients following LT.

Sa1340 Whey Protein Pre-Load Attenuates Post-Prandial Hyperglycemia and Slows Carbohydrate Absorption in Patients With Roux-en-Y Gastric Bypass

Nam Nguyen, Carly M Burgstad, Tamara L Debreceni, Max Bellon, Judith Wishart, Christopher Rayner, Michael Horowitz