Gastric emptying, mouth-to-cecum transit, and glycemic, insulin, incretin, and energy intake responses to a mixed-nutrient liquid in lean, overweight, and obese males.

Observations relating to the impact of obesity on gastric emptying (GE) and the secretion of gut hormones are inconsistent, probably because of a lack of studies in which GE, gastrointestinal hormone release, and energy intake (EI) have been evaluated concurrently with previous patterns of nutrient intake. GE is known to be a major determinant of postprandial glycemia and incretin secretion in health and type 2 diabetes. The aims of this study were to determine the effects of a mixed-nutrient drink on GE, oro-cecal transit, blood glucose, insulin and incretin concentrations and EI, and the relationship between the glycemic response to the drink with GE in lean, overweight, and obese subjects. Twenty lean, 20 overweight, and 20 obese males had measurements of GE, oro-cecal transit, and blood glucose, insulin, GLP-1, and GIP concentrations for 5 h after ingestion of a mixed-nutrient drink (500 ml, 532 kcal); EI at a subsequent buffet lunch was determined. Habitual EI was also quantified. Glycemic and insulinemic responses to the drink were greater in the obese (both P < 0.05) when compared with both lean and overweight, with no significant differences in GE, intragastric distribution, oro-cecal transit, incretins, or EI (buffet lunch or habitual) between groups. The magnitude of the rise in blood glucose after the drink was greater when GE was relatively more rapid (r = -0.55, P < 0.05). In conclusion, in the absence of differences in habitual EI, both GE and incretin hormones are unaffected in the obese despite greater glucose and insulin responses, and GE is a determinant of postprandial glycemia.

Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men.

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

Effects of small intestinal glucose load on blood pressure, splanchnic blood flow, glycemia, and GLP-1 release in healthy older subjects.

Postprandial hypotension is an important problem, particularly in the elderly. The fall in blood pressure is dependent on small intestinal glucose delivery and, possibly, changes in splanchnic blood flow, the release of glucagon-like peptide-1 (GLP-1), and sympathetic nerve activity. We aimed to determine in healthy older subjects, the effects of variations in small intestinal glucose load on blood pressure, superior mesenteric artery flow, GLP-1, and noradrenaline. Twelve subjects (6 male, 6 female; ages 65-76 yr) were studied on four separate occasions, in double-blind, randomized order. On each day, subjects were intubated via an anesthetized nostril, with a nasoduodenal catheter, and received an intraduodenal infusion of either saline (0.9%) or glucose at a rate of 1, 2, or 3 kcal/min (G1, G2, G3, respectively), for 60 min (t = 0-60 min). Between t = 0 and 60 min, there were falls in systolic and diastolic blood pressure following G2 and G3 (P = 0.003 and P < 0.001, respectively), but no change during saline or G1. Superior mesenteric artery flow increased slightly during G1 (P = 0.01) and substantially during G2 (P < 0.001) and G3 (P < 0.001), but not during saline. The GLP-1 response to G3 was much greater (P < 0.001) than to G2 and G1. Noradrenaline increased (P < 0.05) only during G3. In conclusion, in healthy older subjects the duodenal glucose load needs to be > 1 kcal/min to elicit a significant fall in blood pressure, while the response may be maximal when the rate is 2 kcal/min. These observations have implications for the therapeutic strategies to manage postprandial hypotension by modulating gastric emptying.

The oligosaccharide α-cyclodextrin has modest effects to slow gastric emptying and modify the glycaemic response to sucrose in healthy older adults.

In healthy older subjects, the glycaemic response to carbohydrate-containing meals is dependent on gastric emptying and intestinal absorption; when the latter is slowed, the magnitude of the rise in glucose is attenuated. The oligosaccharide α-cyclodextrin has been reported to diminish the glycaemic response to starch in young adults; this effect has been attributed to the inhibition of pancreatic amylase. We examined the effects of α-cyclodextrin on gastric emptying of, and the glycaemic and insulinaemic responses to, oral sucrose in healthy older subjects; as sucrose is hydrolysed by intestinal disaccharides, any effect(s) of α-cyclodextrin would not be attributable to amylase inhibition. A total of ten subjects (seven males and three females, age 68-76 years) were studied on 2 d. Gastric emptying, blood glucose and serum insulin were measured after ingestion of a 300 ml drink containing 100 g sucrose, labelled with (99m)Tc-sulphur colloid, with or without 10 g α-cyclodextrin. Gastric emptying was slowed slightly by α-cyclodextrin; this effect was evident between 135 and 195 min and was associated with a slight increase (P < 0·05) in distal stomach retention. After α-cyclodextrin, blood glucose was slightly less (P < 0·05) at 60 min, and serum insulin was less (P < 0·0005) at 90 and 120 min. There was no difference in the incremental areas under the curve (iAUC) for blood glucose, but there was a trend for the iAUC for serum insulin to be lower (P = 0·09) after α-cyclodextrin. We conclude that in a dose of 10 g, α-cyclodextrin has modest effects to slow gastric emptying of, and modify the glycaemic and insulinaemic responses to, oral sucrose, probably due to delayed intestinal carbohydrate absorption.

Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) attenuates the glycaemic response to small intestinal nutrient infusion in stress-induced hyperglycaemia and reduces fasting glucose concentrations in critically ill patients with type-2 diabetes. The objective of this study was to evaluate the effects of acute administration of GLP-1 on the glycaemic response to small intestinal nutrient infusion in critically ill patients with pre-existing type-2 diabetes. METHODS: Eleven critically ill mechanically-ventilated patients with known type-2 diabetes received intravenous infusions of GLP-1 (1.2 pmol/kg/minute) and placebo from t = 0 to 270 minutes on separate days in randomised double-blind fashion. Between t = 30 to 270 minutes a liquid nutrient was infused intraduodenally at a rate of 1 kcal/min via a naso-enteric catheter. Blood glucose, serum insulin and C-peptide, and plasma glucagon were measured. Data are mean ± SEM. RESULTS: GLP-1 attenuated the overall glycaemic response to nutrient (blood glucose AUC30-270 min: GLP-1 2,244 ± 184 vs. placebo 2,679 ± 233 mmol/l/minute; P = 0.02). Blood glucose was maintained at < 10 mmol/l in 6/11 patients when receiving GLP-1 and 4/11 with placebo. GLP-1 increased serum insulin at 270 minutes (GLP-1: 23.4 ± 6.7 vs. placebo: 16.4 ± 5.5 mU/l; P < 0.05), but had no effect on the change in plasma glucagon. CONCLUSIONS: Exogenous GLP-1 in a dose of 1.2 pmol/kg/minute attenuates the glycaemic response to small intestinal nutrient in critically ill patients with type-2 diabetes. Given the modest magnitude of the reduction in glycaemia the effects of GLP-1 at higher doses and/or when administered in combination with insulin, warrant evaluation in this group. TRIAL REGISTRATION: ANZCTR:ACTRN12610000185066.

Effects of nutritional supplementation on the appetite and energy intake responses to IV cholecystokinin in older adults.

Human aging is associated with a reduction in appetite and food intake. Increased activity of the satiety hormone, cholecystokinin (CCK), may be partly responsible. This study aimed to determine whether an increase in fat and energy intake modifies the suppressive effects of CCK-8 on appetite and energy intake. Fourteen healthy older adults completed three separate dietary periods, a 14-day and a 7-day normal diet (ND; 8272 ± 480 kJ/day; 35% fat), and a 14-day high-fat diet (HFD; 11,642 ± 414 kJ/day; 43% fat), in randomised order. Immediately following each diet, subjects received, in single-blinded fashion, a 30-min intravenous infusion of either CCK-8 (1.5 ng/kg/min) (ND-CCK, HFD-CCK) or 0.9% saline (ND-SAL), the latter following only ND. Plasma CCK concentrations, appetite responses and energy intake at a buffet meal were determined. Energy intake at the buffet meal was higher on the ND-SAL study day (3349 ± 224 kJ), when compared with either ND-CCK (3023 ± 317 kJ) or HFD-CCK (2905 ± 316 kJ). The suppression of energy intake by CCK-8 infusion did not differ between the two diets. We conclude that suppression of energy intake by exogenous CCK-8 does not appear to be attenuated by incorporation of supplemental high-energy, high-fat drinks in the diet of healthy older adults.

Carbohydrate and fat digestion is necessary for maximal suppression of total plasma ghrelin in healthy adults.

It is uncertain whether the postprandial suppression of ghrelin is dependent on digestion and absorption of nutrients or whether the presence of nutrients in the small intestine is sufficient. Twenty-four healthy young adults with a mean age of 23 ± 0.6 years were examined on 3 separate days after an overnight fast. Twelve subjects participated in Part A, and the other 12 subjects in Part B. In Part A, subjects consumed, in random order, one of three study drinks: 300 mL water; 300 mL high-fat drink, with and without, 120 mg orlistat. In Part B, subjects received, in random order, one of three drinks: 300 mL water; 300 mL sucrose, with and without, 100mg acarbose. In both parts gastric emptying as measured by 2-D ultrasound. In Part A, plasma ghrelin concentrations decreased following ingestion of the high-fat drink, but did not change with the high-fat-orlistat drink or water. In Part B, the suppression of plasma ghrelin following the sucrose drink, was attenuated by acarbose. Orlistat accelerated gastric emptying of the high-fat drink, while acarbose delayed gastric emptying of the sucrose drink. In conclusion, fat and carbohydrate digestion is required for maximal suppression of ghrelin secretion.

Effects of the phases of the menstrual cycle on gastric emptying, glycemia, plasma GLP-1 and insulin, and energy intake in healthy lean women.

There is evidence that the menstrual cycle affects appetite, such that energy intake is lower during the follicular compared with the luteal phase. Gastric emptying influences energy intake, glycemia, and plasma glucagon-like peptide-1 (GLP-1), insulin, and cholecystokinin (CCK) release. We hypothesized that 1) gastric emptying of a glucose drink is slower, and glycemia, plasma hormones, hunger, and energy intake are less, during the follicular compared with the luteal phase; 2) the reduction in the latter parameters during the follicular phase are related to slower gastric emptying; and 3) these parameters are reproducible when assessed twice within a particular phase of the menstrual cycle. Nine healthy, lean women were studied on three separate occasions: twice during the follicular phase (days 6-12) and once during the luteal phase (days 18-24). Following consumption of a 300-ml glucose drink (0.17 g/ml), gastric emptying, blood glucose, plasma hormone concentrations, and hunger were measured for 90 min, after which energy intake at a buffet meal was quantified. During the follicular phase, gastric emptying was slower (P < 0.05), and blood glucose (P < 0.01), plasma GLP-1 and insulin (P < 0.05), hunger (P < 0.01), and energy intake (P < 0.05) were lower compared with the luteal phase, with no differences for CCK or between the two follicular phase visits. There were inverse relationships between energy intake, blood glucose, and plasma GLP-1 and insulin concentrations with the amount of glucose drink remaining in the stomach at t = 90 min (r < -0.6, P < 0.05). In conclusion, in healthy women 1) gastric emptying of glucose is slower, and glycemia, plasma GLP-1 and insulin, hunger, and energy intake are less during the follicular compared with the luteal phase; 2) energy intake, glycemia, and plasma GLP-1 and insulin are related to gastric emptying; and 3) these parameters are reproducible when assessed twice during the follicular phase.

Reproducibility of energy intake, gastric emptying, blood glucose, plasma insulin and cholecystokinin responses in healthy young males.

Gastric emptying, as well as intragastric meal distribution, and gastrointestinal hormones, including cholecystokinin (CCK), play an important role in appetite regulation. The evaluation of gastrointestinal factors regulating food intake is commonly performed in healthy, lean, young male participants. It has, however, been suggested that there is a marked interindividual variability in the effects of nutrient 'preloads' on energy intake in this group. Whether there is significant intraindividual variation in acute energy intake after a nutrient preload, and, if so, how this relates to day-to-day differences in gastric emptying and gastrointestinal hormone release, is unclear. The purpose of the present paper is to evaluate the hypothesis that energy intake after a nutrient preload would be reproducible and associated with reproducible patterns of gastric emptying, intragastric distribution and gastrointestinal hormone release. Fifteen healthy men (age 25 (sem 5) years) consumed a glucose preload (50 g glucose in 300 ml water; 815 kJ) on three occasions. Gastric emptying and intragastric meal distribution (using three-dimensional ultrasound), blood glucose, plasma insulin and CCK concentrations and appetite perceptions were evaluated over 90 min, and energy intake from a cold buffet-style meal was then quantified. Energy intake was highly reproducible within individuals between visits (intraclass correlation coefficient, ri = 0.9). Gastric emptying, intragastric meal distribution, blood glucose, plasma insulin and CCK concentrations and appetite perceptions did not differ between visits (ri>0.7 for all). In healthy males, energy intake is highly reproducible, at least in the short term, and is associated with reproducible patterns of gastric emptying, glycaemia, insulinaemia and CCK release.

Fasting ghrelin is related to skeletal muscle mass in healthy adults.

BACKGROUND/OBJECTIVES: The determinants of plasma ghrelin concentrations including the effects of aging, gender, and body composition, are unclear. Appetite and energy intake decrease with advancing age, and there is a corresponding decline in total body lean tissue, and an increase in fat mass. METHODS: We measured fasting plasma ghrelin and insulin concentrations in 52 healthy subjects aged 22-82 years, and assessed body composition by dual energy X-ray absorptiometry. Energy intake was estimated from diet diaries. RESULTS: Fasting ghrelin concentrations were not significantly correlated with age and energy intake (R = 0.07, P = 0.62; and R = -0.14, P = 0.34 respectively) on univariate regression analysis, and ghrelin concentrations were higher in females than males (2886.8 +/- 182.1 pg/ml vs 2082.5 +/- 121.2 pg/ml; P = 0.001). Ghrelin was inversely related to body mass index (R = -0.328, P = 0.018), fat-free body mass (R = -0.428, P = 0.002), and total skeletal muscle mass (R = -0.439, P = 0.001), but not related to body fat mass (R = 0.177, P = 0.208). On multiple regression analysis, total skeletal muscle mass (corrected for height) was the only significant negative predictor (P < 0.0001) of fasting ghrelin concentrations. CONCLUSIONS: In conclusion, in healthy adults, plasma ghrelin concentrations are not significantly influenced by age or energy intake per se, but relate to skeletal muscle mass.

Functional dyspepsia is associated with a greater symptomatic response to fat but not carbohydrate, increased fasting and postprandial CCK, and diminished PYY.

BACKGROUND/OBJECTIVES: In patients with functional dyspepsia (FD), symptoms are frequently triggered, or exacerbated, by fatty foods. We hypothesized that in FD patients, a high-fat (high-FAT) meal would induce more symptoms than a high-carbohydrate (high-CHO) meal, associated with an altered secretion of cholecystokinin (CCK), peptide-YY (PYY), and ghrelin and an increased antral size, when compared to healthy subjects (HS). METHODS: FD symptoms, appetite perceptions, plasma hormones, and antral area were measured in 8 FD patients and 8 HS on three separate days after the ingestion of high-CHO or high-FAT (500 kcal/400 g) meals, or a low-nutrient control (180 kcal/400 g); the energy intake was quantified 60 min later. RESULTS: Nausea (P < 0.01) and pain (P= 0.05) were greater in FD after the high-FAT, when compared to high-CHO and control meals and in HS. Discomfort was greater after all meals in FD when compared to HS (P < 0.05). Fasting CCK and stimulation of CCK by the high-FAT (P < 0.01) meal were greater in FD, while fasting and postprandial PYY were lower (P < 0.001) in FD than in HS, with no differences in fasting, or postprandial, plasma ghrelin between FD and HS. Fasting antral area was greater in FD (P < 0.05), with no differences postprandially between FD and HS. There were no differences in the energy intake between the two groups. CONCLUSIONS: In FD patients: (a) a high-FAT meal induces more symptoms than an isocaloric high-CHO meal, and (b) fasting and postprandial plasma CCK concentrations are greater and PYY concentrations are less. Our findings have important implications for the development of diet-based therapies for the treatment of FD.

Transient, early release of glucagon-like peptide-1 during low rates of intraduodenal glucose delivery.

CONTEXT: The "incretin" hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), account for some 60% of the stimulation of insulin by oral glucose, but the determinants of their secretion from the small intestine are poorly understood. Cells which release GIP (K cells) are localized to the proximal small intestine, while GLP-1 releasing cells (L cells) predominate in the distal gut. It has been suggested that a threshold rate of duodenal glucose delivery (approximately 1.8 kcal/min) needs to be exceeded for stimulation of GLP-1. OBJECTIVE: To determine whether a low intraduodenal glucose load (1 kcal/min) has the capacity to stimulate GLP-1, and if so, the characteristics of the response. DESIGN: Retrospective analysis of all studies in our laboratory involving healthy humans administered intraduodenal glucose at 1 kcal/min for 120 min. SETTING: Clinical research laboratory. PARTICIPANTS: 27 healthy subjects (24 male; age 36+/-3 years; BMI 25.2+/-0.7 kg/m(2)). MAIN OUTCOME MEASURES: Plasma GLP-1, GIP, insulin, and blood glucose concentrations, reported as mean+/-SEM. RESULTS: During intraduodenal glucose, plasma GLP-1 increased at 15 and 30 min (P<0.001 for both) and returned to baseline thereafter. In contrast, there were sustained increases in plasma GIP (P<0.001), insulin (P<0.001), and blood glucose (P<0.001). CONCLUSION: In healthy subjects, there is early, transient stimulation of GLP-1 by glucose loads hitherto believed to be "sub-threshold". The mechanisms underlying this effect, which could be attributed to initially rapid transit to jejunal L cells, or a duodeno-jejunoileal neural or hormonal loop, remain to be determined.

Effects of protein on glycemic and incretin responses and gastric emptying after oral glucose in healthy subjects.

BACKGROUND: Dietary interventions represent a promising therapeutic strategy to optimize postprandial glycemia. The addition of protein to oral glucose has been reported to improve the glycemic profile. OBJECTIVE: The aim of the current study was to evaluate the mechanisms by which protein supplementation lowers the blood glucose response to oral glucose. DESIGN: Nine healthy men were studied on 3 d each in a random order. Subjects consumed 300-mL drinks containing either 50 g glucose (Glucose), 30 g gelatin (Protein), or 50 g glucose with 30 g gelatin (Glucose + Protein) in water labeled with 150 mg [(13)C]acetate. Blood and breath samples were subsequently collected for 3 h to measure blood glucose and plasma insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations and gastric half-emptying time, which was calculated from (13)CO(2) excretion. RESULTS: The blood glucose response was less after Glucose + Protein than after Glucose (P < 0.005); GIP was lower (P < 0.005), and there were no significant differences in plasma insulin or GLP-1. Protein alone stimulated insulin, GLP-1, and GIP (P < 0.05 for each) without elevating blood glucose. The gastric half-emptying time was greater after Glucose + Protein than after Glucose (P < 0.05) and tended to be greater for Glucose than for Protein (P = 0.06). CONCLUSIONS: In healthy humans, the addition of protein to oral glucose lowers postprandial blood glucose concentrations acutely, predominantly by slowing gastric emptying, although protein also stimulates incretin hormones and non-glucose-dependent insulin release.

Effects of fat on gastric emptying of and the glycemic, insulin, and incretin responses to a carbohydrate meal in type 2 diabetes.

CONTEXT: Gastric emptying (GE) is a major determinant of postprandial glycemia. Because the presence of fat in the small intestine inhibits GE, ingestion of fat may attenuate the glycemic response to carbohydrate. OBJECTIVE: The objective of this study was to evaluate the effect of patterns of fat consumption on GE and glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations after a carbohydrate meal in type 2 diabetes. DESIGN: This was a randomized, cross-over study in which GE of a radioisotopically labeled potato meal was measured on 3 d. SETTING: The study was performed at the Royal Adelaide Hospital. PATIENTS: Six males with type 2 diabetes were studied. INTERVENTION: Subjects ingested 1) 30 ml water 30 min before the mashed potato (water), 2) 30 ml olive oil 30 min before the mashed potato (oil), or 3) 30 ml water 30 min before the mashed potato meal that contained 30 ml olive oil (water and oil). MAIN OUTCOME MEASURES: GE, blood glucose, plasma insulin, GLP-1, and GIP concentrations were the main outcome measures. RESULTS: GE was much slower with oil compared with both water (P < 0.0001) and water and oil (P < 0.05) and was slower after water and oil compared with water (P < 0.01). The postprandial rise in blood glucose was markedly delayed (P = 0.03), and peak glucose occurred later (P = 0.04) with oil compared with the two other meals. The rises in insulin and GIP were attenuated (P < 0.0001), whereas the GLP-1 response was greater (P = 0.0001), after oil. CONCLUSIONS: Ingestion of fat before a carbohydrate meal markedly slows GE and attenuates the postprandial rises in glucose, insulin, and GIP, but stimulates GLP-1, in type 2 diabetes.

Effects of Fat and Protein Preloads on Pouch Emptying, Intestinal Transit, Glycaemia, Gut Hormones, Glucose Absorption, Blood Pressure and Gastrointestinal Symptoms After Roux-en-Y Gastric Bypass.

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.

Effects of Posture and Meal Volume on Gastric Emptying, Intestinal Transit, Oral Glucose Tolerance, Blood Pressure and Gastrointestinal Symptoms After Roux-en-Y Gastric Bypass.

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.

Relationships of Early And Late Glycemic Responses With Gastric Emptying During An Oral Glucose Tolerance Test.

CONTEXT: The early glycemic response during a 75-g oral glucose tolerance test (OGTT) is directly related to the rate of gastric emptying (GE). There is little information about the effect of GE on the blood glucose at either 60 min (a predictor of diabetes) or 120 min (used diagnostically). OBJECTIVE: This study aimed to evaluate the relationships between glycemic responses at 30, 60, and 120 min and GE following a 75-g OGTT in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2D). DESIGN, SETTING, AND SUBJECTS: Eighty-two subjects in the general community without diabetes (57 NGT, 25 IGT) and 16 with T2D consumed a 75-g glucose drink labeled with (99m)Tc-sulfur colloid. GE (by scintigraphy) and glycemia were measured from t = 0-120 min and relationships between blood glucose (absolute, change from baseline, and area under the curve) and GE at 30, 60, and 120 min determined. RESULTS: There were no differences in GE. There were relationships between the blood glucose at 30 min and GE (NGT: r = 0.40; P < .01; IGT: r = 0.49; P = .02; T2D: r = 0.62; P = .01). There was also a relationship between the blood glucose at 60 min and GE in IGT (r = 0.52; P = .02) and T2D (r = 0.77; P < .01), but not NGT (r = 0.16; P = .24). In NGT, there was an inverse relationship between blood glucose at 120 min and GE (r = -0.30; P = .02), but not in IGT (r = 0.05; P = .82) or T2D (r = 0.37; P = .16). CONCLUSIONS: GE is a determinant of the glycemic response to an OGTT in NGT, IGT, and T2D but these relationships differ and are time dependent.

Effect of variations in small intestinal glucose delivery on plasma glucose, insulin, and incretin hormones in healthy subjects and type 2 diabetes.

The determinants of postprandial blood glycemia are controversial. We assessed the effects of variations in the initial rate of small intestinal glucose delivery on blood glucose, plasma insulin, and incretin responses in both health and type 2 diabetes. Eight controls and eight patients with type 2 diabetes managed by diet alone underwent paired studies. On both days subjects received an intraduodenal glucose infusion (t = 0-120 min); on one day the infusion rate was variable, being more rapid initially (3 kcal/min) between t = 0 and 15 min and slower (0.71 kcal/min) subsequently (t = 15-120 min), whereas on the other day, the infusion rate was constant (1 kcal/min) from t = 0 to 120 min (i.e. on both days 120 kcal of glucose were administered). Between t = 0-180 min blood glucose, plasma insulin and plasma glucose-dependent insulin-releasing polypeptide were greater with the variable, compared with the constant, infusion. Between t = 0 and 30 min the magnitude of the rise in plasma glucagon-like peptide-1 was greater with the variable, compared with the constant infusion (P < 0.01, both groups). We conclude that modest variations in the initial rate of duodenal glucose entry may have profound effects on subsequent glycemic, insulin, and incretin responses.

A longitudinal study of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus.

PURPOSE: To evaluate the natural history of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. SUBJECTS AND METHODS: We enrolled 20 patients (6 men, 14 women) with diabetes mellitus (16 with type 1 diabetes, 4 with type 2 diabetes). Each had measurements of gastric emptying of a solid (100 g of ground beef) and liquid (150 mL of 10% dextrose) meal using scintigraphy, glycemic control (glycosylated hemoglobin [HbA(1c)] and mean blood glucose levels), upper gastrointestinal symptoms, and autonomic nerve function at baseline and after a mean (+/- SD) of 12.3 +/- 3.1 years of follow-up. RESULTS: There were no differences in mean gastric emptying of the solid component (retention at 100 minutes at baseline: 56% +/- 19% vs. follow-up: 51% +/- 21%, P = 0.23) or the liquid component (time for 50% to empty at baseline: 33 +/- 11 minutes vs. follow-up: 31 +/- 12 minutes, P = 0.71) during follow-up. Mean blood glucose (17.0 +/- 5.6 mmol/L vs. 13.8 +/- 4.9 mmol/L, P = 0.007) and HbA(1c) (8.4% +/- 2.3% vs. 7.6% +/- 1.3%, P = 0.03) levels were lower at follow-up. There was no difference in symptom score (baseline: 3.9 +/- 2.7 vs. follow-up: 4.2 +/- 4.0, P = 0.78). There was evidence of autonomic neuropathy in 7 patients (35%) at baseline and 16 (80%) at follow-up. CONCLUSION: In patients with diabetes mellitus, we did not observe any marked changes in either gastric emptying or upper gastrointestinal symptoms during a 12-year period.

Glycemic, hormone, and appetite responses to monosaccharide ingestion in patients with type 2 diabetes.

To investigate the relative effects of fructose and glucose on blood glucose, plasma insulin and incretin (glucagon-like peptide-1 [GLP-1] and gastric inhibitory peptide [GIP]) concentrations, and acute food intake, 10 (6 men, 4 women) patients with diet-controlled type 2 diabetes (diabetic) (44 to 71 years) and 10 age and body mass index (BMI)-matched (6 men, 4 women) nondiabetic, control subjects with varying degrees of glucose tolerance (nondiabetic), were studied on 3 days. In random order, they drank equienergetic preloads of glucose (75 g) (GLUC), fructose (75 g) (FRUCT) or vehicle (300 mL water with noncaloric flavoring [VEH]) 3 hours before an ad libitum buffet lunch. Mean glucose concentrations were lower after FRUCT than GLUC in both type 2 diabetics (FRUCT v GLUC: 7.5 +/- 0.3 v 10.8 +/- 0.4 mmol/L, P <.001) and nondiabetics (FRUCT v GLUC: 5.9 +/- 0.2 v 7.2 +/- 0.3 mmol/L, P <.05). Mean insulin concentrations were approximately 50% higher after FRUCT in type 2 diabetics than in nondiabetics (diabetics v nondiabetics: 23.1 +/- 0.7 v 15.1 +/- 1.3 microU/mL; P <.0001). Plasma GLP-1 concentrations after fructose were not different between type 2 diabetics and nondiabetics (P >.05). Glucose, but not FRUC, increased GIP concentrations, which were not different between type 2 diabetics and nondiabetics (P >.05). Food intake was suppressed 14% by GLUC (P <.05 v CONT) and 14% by FRUC (P <.05 v CONT), with no difference between the amount of food consumed after GLUC and FRUC treatment in either type 2 diabetics or nondiabetics (P >.05). We have confirmed that oral fructose ingestion produces a lower postprandial blood glucose response than equienergetic glucose and demonstrated that (1) fructose produces greater increases in plasma insulin concentration in type 2 diabetics than nondiabetics, not apparently due to greater plasma incretin concentrations and (2) fructose and glucose have equivalent short-term satiating efficiency in both type 2 diabetics and nondiabetics. We conclude that on the basis of improved glycemic control, but not satiating efficiency, fructose may be useful as a replacement for glucose in the diet of obese patients with type 2 diabetes.