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1.
Int J Obes (Lond) ; 42(9): 1556-1564, 2018 09.
Article in English | MEDLINE | ID: mdl-29453463

ABSTRACT

OBJECTIVE: This study evaluated gastric emptying (GE) and small intestinal (SI) transit in people with morbid obesity and their relationships to glycaemia, incretin hormones, and glucose absorption METHODS: GE and caecal arrival time (CAT) of a mixed meal were assessed in 22 morbidly obese (50.2 ± 2.5 years; 13 F:9 M; BMI: 48.6 ± 1.8 kg/m2) and 10 lean (38.6 ± 8.4 years; 5 F:5 M; BMI: 23.9 ± 0.7 kg/m2) subjects, using scintigraphy. Blood glucose, plasma 3-O-methylglucose, insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured. Insulin sensitivity and resistance were also quantified RESULTS: When compared with lean subjects, GE (t50: 60.7 ± 6.5 vs. 41.1 ± 7.3 min; P = 0.04) and CAT (221.5 ± 9.8 vs. 148.0 ± 7.1 min; P = 0.001) of solids were prolonged in morbid obesity. Postprandial rises in GIP (P = 0.001), insulin (P = 0.02), glucose (P = 0.03) and 3-O-methylglucose (P = 0.001) were less. Whereas GLP-1 increased at 45 mins post-prandially in lean subjects, there was no increase in the obese (P = 0.04). Both fasting (P = 0.045) and postprandial (P = 0.012) plasma glucagon concentrations were higher in the obese CONCLUSIONS: GE and SI transit are slower in the morbidly obese, and associated with reductions in postprandial glucose absorption, and glycaemic excursions, as well as plasma GIP and GLP-1.


Subject(s)
Blood Glucose/metabolism , Gastric Emptying/physiology , Gastrointestinal Hormones/metabolism , Gastrointestinal Transit/physiology , Obesity, Morbid , Adult , Female , Humans , Intestine, Small/metabolism , Male , Middle Aged , Obesity, Morbid/metabolism , Obesity, Morbid/physiopathology , Radionuclide Imaging
2.
Endosc Int Open ; 4(11): E1171-E1177, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27853742

ABSTRACT

Background and study aims: Colonoscopy with portal inhaled methoxyflurane (Penthrox) is highly feasible with low sedation risk and allows earlier discharge. It is unclear if subjects can return to highly skilled psychomotor skill task shortly after Penthrox assisted colonoscopy. We evaluated the psychomotor and cognitive effects of 15-minute inhalation of Penthrox in adults. Patients and methods: Sixty healthy volunteers (18 to 80 years) were studied on 2 occasions with either Penthrox or placebo in a randomized, double-blind fashion. On each occasion, the subject's psychomotor function was examined before, immediately, 30, 60, 120, 180 and 240 min after a 15-minute inhalation of studied drug, using validated psychomotor tests (Digit Symbol Substitution Test (DSST), auditory reaction time (ART), eye-hand coordination (EHC) test, trail making test (TMT) and logical reasoning test (LRT). Results: Compared to placebo, a 15-minute Penthrox inhalation led to an immediate but small impairment of DSST (P < 0.001), ART (P < 0.001), EHC (P < 0.01), TMT (P = 0.02) and LRT (P = 0.04). In all subjects, the performance of all 5 tests normalized by 30 minutes after inhalation, and was comparable to that with placebo. Although increasing age was associated with a small deterioration in psychomotor testing performance, the magnitude of Penthrox effects remained comparable among all age groups. Conclusions: In all age groups, a 15-minute Penthrox inhalation induces acute but short-lasting impairment of psychomotor and cognitive performance, which returns to normal within 30 minutes , indicating that subjects who have colonoscopy with Penthrox can return to highly skilled psychomotor skills tasks such as driving and daily work the same day.

3.
Obes Surg ; 26(1): 77-84, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25986427

ABSTRACT

BACKGROUND: The aim was to determine the effects of fat and protein preloads on pouch emptying (PE), caecal arrival time (CAT), glucose absorption, blood glucose (BSL), gut hormones, haemodynamics and gastrointestinal (GI) symptoms in subjects who had undergone Roux-en-Y gastric bypass (RYGB) >12 months previously. METHODS: Ten RYGB subjects were studied on three occasions, in randomised order, receiving 200-ml preloads of either water, fat (30 ml olive oil) or whey protein (55 g), 30 min before a mixed meal. PE, CAT, BSL, plasma 3-O-methyl-D-glucopyranose (3-OMG), insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon, blood pressure (BP), heart rate (HR) and GI symptoms were assessed over 270 min. RESULTS: Although fat and protein preloads did not alter PE of either solids or liquids, the CAT of solids, but not liquids, was longer than that after the water preload (fat 68 ± 5 min and protein 71 ± 6 min vs. water 46 ± 5 min; P = 0.02). BSL elevated promptly after the meal on all days (P < 0.001), but after protein, the magnitude and integrated increases in the first 75 min were less than fat and water preloads (area under the curve (AUC(0-75 min)), 18.7 ± 18.2 vs. 107.2 ± 30.4 and 76.1 ± 19.3 mmol/L/min; P < 0.05). Compared to water preload, the protein and fat preloads were associated with greater increases in plasma insulin, GLP-1 and glucagon concentrations, a reduction in BP, and greater increases in HR, fullness, bloating and nausea. Plasma 3-OMG levels were lower after the protein than after the water and fat preloads (P < 0.001). CONCLUSIONS: Given its effects to attenuate post-prandial glycaemia, reduce intestinal glucose absorption and potentiate the "incretin response", without inducing more adverse post-prandial GI symptom, protein preload may prove clinically useful in RYGB patients and warrant further evaluation, particularly in those with type 2 diabetes (T2DM) and/or dumping syndrome.


Subject(s)
Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Gastric Bypass , Blood Glucose/analysis , Blood Pressure , Female , Gastrointestinal Transit , Glucagon/blood , Glucagon-Like Peptide 1/blood , Heart Rate , Humans , Insulin/blood , Male , Middle Aged , Nausea , Water
4.
J Clin Endocrinol Metab ; 100(3): 968-76, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25423571

ABSTRACT

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.


Subject(s)
Blood Glucose/metabolism , Glucose Transport Proteins, Facilitative/genetics , Glucose/metabolism , Incretins/blood , Intestinal Absorption , Obesity, Morbid/metabolism , 3-O-Methylglucose/pharmacokinetics , Adult , Female , Gastric Inhibitory Polypeptide/blood , Gene Expression , Glucagon/blood , Glucagon-Like Peptide 1/blood , Glucose Transport Proteins, Facilitative/metabolism , Humans , Insulin/blood , Male , Middle Aged , Obesity, Morbid/genetics , Time Factors
5.
Obes Surg ; 25(8): 1392-400, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25502436

ABSTRACT

BACKGROUND: The purpose of this study is to determine the effects of posture and drink volume on gastric/pouch emptying (G/PE), intestinal transit, hormones, absorption, glycaemia, blood pressure and gastrointestinal (GI) symptoms after gastric bypass (Roux-en-Y gastric bypass (RYGB)). METHODS: Ten RYGB subjects were studied on four occasions in randomized order (sitting vs. supine posture; 50 vs. 150 ml of labelled water mixed with 3 g 3-O-methyl-D-glucose (3-OMG) and 50 g glucose). G/PE, caecal arrival time (CAT), blood glucose, plasma insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), 3-OMG, blood pressure, heart rate and GI symptoms were assessed over 240 min. Controls were ten volunteers with no medical condition or previous abdominal surgery, who were studied with the 150-ml drink in the sitting position. RESULTS: Compared to controls, PE (P < 0.001) and CAT (P < 0.001) were substantially more rapid in RYGB subjects. In RYGB, PE was more rapid in the sitting position (2.5 ± 0.7 vs. 16.6 ± 5.3 min, P = 0.02) and tends to be faster after 150 ml than the 50-ml drinks (9.5 ± 2.9 vs. 14.0 ± 3.5 min, P = 0.16). The sitting position and larger volume drinks were associated with greater releases of insulin, GLP-1 and PYY, as well as more hypotension (P < 0.01), tachycardia (P < 0.01) and postprandial symptoms (P < 0.001). CONCLUSIONS: Pouch emptying, blood pressure and GI symptoms after RYGB are dependent on both posture and meal volume.


Subject(s)
Blood Glucose/metabolism , Blood Pressure/physiology , Gastric Bypass/adverse effects , Gastric Emptying/physiology , Gastrointestinal Diseases/etiology , Gastrointestinal Transit/physiology , Meals/physiology , Obesity, Morbid/surgery , Posture/physiology , Adult , Female , Gastrointestinal Diseases/epidemiology , Glucose Tolerance Test , Humans , Insulin/blood , Male , Middle Aged , Obesity, Morbid/epidemiology , Obesity, Morbid/physiopathology , Postprandial Period , Random Allocation
6.
Obesity (Silver Spring) ; 22(10): 2164-71, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24990218

ABSTRACT

OBJECTIVE: 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. METHODS: Intestinal biopsies were collected for mRNA expression of STR (T1R2) and GTs (SGLT-1 and GLUT2) from 11 non-diabetic RYGB, 13 non-diabetic obese, and 11 healthy subjects, at baseline and following a 30 min small intestinal (SI) glucose infusion (30 g/150 ml water with 3 g 3-O-methyl-d-glucopyranose (3-OMG)). Blood glucose, plasma 3-OMG, and insulin were measured for 270 min. RESULTS: In RYGB patients, expression of both GTs was ∼2-fold higher at baseline and after glucose infusion than those of morbidly obese or healthy subjects (P < 0.001). STR expressions were comparable amongst the groups. Peak plasma 3-OMG in both RYGB (r = 0.69, P = 0.01) and obese (r = 0.72, P = 0.005) correlated with baseline expression of SGLT-1, as was the case with peak blood glucose in RYGB subjects (r = 0.69, P = 0.02). CONCLUSIONS: The upregulated intestinal GTs in RYGB patients are associated with increased glucose absorption when glucose is delivered at a physiological rate, suggesting a molecular adaptation to prevent carbohydrate malabsorption from rapid intestinal transit after RYGB.


Subject(s)
Gastric Bypass , Glucose Transport Proteins, Facilitative/genetics , Intestinal Absorption , Intestinal Mucosa/metabolism , Malabsorption Syndromes/prevention & control , Obesity, Morbid/surgery , Adult , Blood Glucose/metabolism , Carbohydrate Metabolism , Case-Control Studies , Female , Gastric Bypass/adverse effects , Glucose/pharmacokinetics , Glucose Transport Proteins, Facilitative/metabolism , Humans , Insulin/blood , Malabsorption Syndromes/genetics , Malabsorption Syndromes/metabolism , Male , Middle Aged , Obesity, Morbid/genetics , Obesity, Morbid/metabolism , Up-Regulation/genetics
7.
Obesity (Silver Spring) ; 22(9): 2003-9, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24829088

ABSTRACT

OBJECTIVE: 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. METHODS: Ten RYGB patients were studied twice in random order, receiving either a 150 ml glucose drink (200 kcal) or the same solution infused into the proximal Roux-limb at 4 kcal/min. Data were compared with 10 healthy volunteers who received a 4 kcal/min duodenal infusion. PE, cecal arrival time (CAT), blood glucose, plasma 3-O-methylglucose (3-OMG), insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), and GI symptoms were measured. RESULTS: In RYGB subjects, the glucose drink emptied very rapidly (PE t50 = 3 ± 1 min) and intestinal glucose infusion was associated with higher blood glucose and plasma 3-OMG, but lower plasma GLP-1, GIP, insulin, and GI symptoms than oral glucose (all P < 0.001), and comparable to volunteers. In RYGB subjects, CAT correlated inversely with peak GLP-1 (r = -0.73, P = 0.01), and plasma 3-OMG correlated tightly blood glucose (r = 0.94, P < 0.0001). CONCLUSIONS: After RYGB, reducing intestinal glucose delivery to 4 kcal/min is associated with higher blood glucose, greater glucose absorption, lower incretin responses, and less GI symptoms, supporting rapid transit contribution to the exaggerated incretin responses and "dumping symptoms".


Subject(s)
Blood Glucose/metabolism , Dumping Syndrome/etiology , Gastric Bypass , Gastrointestinal Hormones/blood , Gastrointestinal Transit/physiology , Glucose/pharmacokinetics , Intestinal Absorption , Adult , Dumping Syndrome/metabolism , Dumping Syndrome/physiopathology , Female , Gastric Bypass/adverse effects , Gastric Bypass/rehabilitation , Humans , Insulin/blood , Male , Middle Aged , Postprandial Period , Time Factors
8.
World J Gastroenterol ; 19(36): 6035-43, 2013 Sep 28.
Article in English | MEDLINE | ID: mdl-24106404

ABSTRACT

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.


Subject(s)
Gastric Bypass , Laparoscopy , Obesity/surgery , Weight Loss , Adult , Biomarkers/blood , Blood Glucose/metabolism , Body Mass Index , Chi-Square Distribution , Cholesterol/blood , Comorbidity , Female , Gastric Bypass/adverse effects , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/surgery , Humans , Kaplan-Meier Estimate , Laparoscopy/adverse effects , Lipoproteins, LDL/blood , Male , Obesity/blood , Obesity/diagnosis , Reoperation , Risk Factors , Sex Factors , Surgical Wound Infection/etiology , Surgical Wound Infection/surgery , Time Factors , Treatment Outcome
9.
Gastrointest Endosc ; 78(6): 892-901, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23810328

ABSTRACT

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.


Subject(s)
Analgesia, Patient-Controlled , Anesthetics, Inhalation/administration & dosage , Anesthetics, Intravenous/administration & dosage , Colonoscopy/methods , Conscious Sedation , Methoxyflurane/administration & dosage , Administration, Inhalation , Analgesia, Patient-Controlled/adverse effects , Anesthesia Recovery Period , Anesthetics, Inhalation/adverse effects , Anesthetics, Intravenous/adverse effects , Anxiety/diagnosis , Female , Fentanyl , Humans , Male , Methoxyflurane/adverse effects , Midazolam , Middle Aged , Oxygen/blood , Pain Measurement , Patient Satisfaction
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