Impact of gastric emptying to the glycemic and insulinemic responses to a 75-g oral glucose load in older subjects with normal and impaired glucose tolerance

The majority of studies relating to the oral glucose tolerance test (OGTT) have not taken gastric emptying (GE), which exhibits a substantial inter-individual variation, into account. We sought to evaluate the impact of GE, on the glycemic and insulinemic responses to a 75-g oral glucose load in older subjects with normal and impaired glucose tolerance. Eighty-seven healthy 'older' subjects (47F, 40M; age 71.0 ± 0.5 year) were given a drink comprising of 75-g glucose and 150 mg C(13)-acetate made up to 300 mL with water on a single occasion. Exhaled breath was obtained for analysis of (13)CO2 and calculation of the 50% GE time (T50). Blood glucose, serum insulin and plasma glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured, and the insulin sensitivity index (ISI), and the disposition index (DI), were calculated. Thirty-one subjects had normal glucose tolerance (NGT) and 46 had impaired glucose tolerance (IGT). Blood glucose at t = 60 min and t = 120 min were related inversely to ISI (P < 0.001) and DI P < 0.001). The rise in blood glucose at t = 60 min was related inversely to the T50 in all subjects (P < 0.01), and those with IGT (P < 0.001), but not NGT. There were no significant relationships between the blood glucose at t = 120 min with the T50, but in both groups the change in blood glucose from baseline at t = 180 min was related (NGT: P < 0.001; IGT: P < 0.001) to the T50. We conclude that in NGT and IGT, the effect of GE on both the 'early' and 'late' glycemic responses to a 75-g oral glucose load is complementary to that of insulin sensitivity.Laurence G. Trahair, Michael Horowitz, Chinmay S. Marathe, Kylie Lange, Scott Standfield, Christopher K. Rayner, Karen L. Jone

Dose-dependent effects of randomized intraduodenal whey-protein loads on glucose, gut hormone, and amino acid concentrations in healthy older and younger men

Protein-rich supplements are used widely for the prevention and management of malnutrition in older people. We have reported that healthy older, compared to younger, adults have less suppression of energy intake by whey-protein-effects on appetite-related hormones are unknown. The objective was to determine the effects of intraduodenally administered whey-protein on glucose, gut hormone, and amino acid concentrations, and their relation to subsequent ad libitum energy intake at a buffet meal, in healthy older and younger men. Hydrolyzed whey-protein (30 kcal, 90 kcal, and 180 kcal) and a saline control (~0 kcal) were infused intraduodenally for 60 min in 10 younger (19-29 years, 73 ± 2 kg, 22 ± 1 kg/m²) and 10 older (68-81 years, 79 ± 2 kg, 26 ± 1 kg/m²) healthy men in a randomized, double-blind fashion. Plasma insulin, glucagon, gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), and amino acid concentrations, but not blood glucose, increased, while ghrelin decreased during the whey-protein infusions. Plasma GIP concentrations were greater in older than younger men. Energy intake correlated positively with plasma ghrelin and negatively with insulin, glucagon, GIP, GLP-1, PYY, and amino acids concentrations (p < 0.05). In conclusion, intraduodenal whey-protein infusions resulted in increased GIP and comparable ghrelin, insulin, glucagon, GIP, GLP-1, PYY, and amino acid responses in healthy older and younger men, which correlated to subsequent energy intake.Caroline Giezenaar, Natalie D Luscombe-Marsh, Amy T Hutchison, Scott Standfield, Christine Feinle-Bisset, Michael Horowitz, Ian Chapman and Stijn Soene

Effects of a D-xylose preload with or without sitagliptin on gastric emptying, glucagon-like peptide-1, and postprandial glycemia in type 2 diabetes

OBJECTIVE Macronutrient “preloads” can reduce postprandial glycemia by slowing gastric emptying and stimulating glucagon-like peptide-1 (GLP-1) secretion. An ideal preload would entail minimal additional energy intake and might be optimized by concurrent inhibition of dipeptidyl peptidase-4 (DPP-4). We evaluated the effects of a low-energy d-xylose preload, with or without sitagliptin, on gastric emptying, plasma intact GLP-1 concentrations, and postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS Twelve type 2 diabetic patients were studied on four occasions each. After 100 mg sitagliptin (S) or placebo (P) and an overnight fast, patients consumed a preload drink containing either 50 g d-xylose (X) or 80 mg sucralose (control [C]), followed after 40 min by a mashed potato meal labeled with 13C-octanoate. Blood was sampled at intervals. Gastric emptying was determined. RESULTS Both peak blood glucose and the amplitude of glycemic excursion were lower after PX and SC than PC (P < 0.01 for each) and were lowest after SX (P < 0.05 for each), while overall blood glucose was lower after SX than PC (P < 0.05). The postprandial insulin-to-glucose ratio was attenuated (P < 0.05) and gastric emptying was slower (P < 0.01) after d-xylose, without any effect of sitagliptin. Plasma GLP-1 concentrations were higher after d-xylose than control only before the meal (P < 0.05) but were sustained postprandially when combined with sitagliptin (P < 0.05). CONCLUSIONS In type 2 diabetes, acute administration of a d-xylose preload reduces postprandial glycemia and enhances the effect of a DPP-4 inhibitor.Tongzhi Wu, Michelle J. Bound, Beiyi R. Zhao, Scott D. Standfield, Max Bellon, Karen L. Jones, Michael Horowitz, Christopher K. Rayne

Effect of gastric distension with concurrent small intestinal saline or glucose infusion on incretin hormone secretion in healthy individuals - a randomised, controlled, cross-over study.

Aims There is increasing interest in the use of intragastric balloons as a weight loss procedure, however, the underlying mechanism(s) remain unclear. In rodents, gastric distension has recently been shown to stimulate the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) substantially, but the effect of gastric distension on GLP-1 and the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), in humans is not known. We conducted a randomized, controlled, crossover study to evaluate the effect of gastric distension, induced using a gastric 'barostat' on incretin hormones in healthy individuals Materials and methods Eight healthy participants (2 female, 6 male, mean age 69.3±1.2 years, and body mass index 23.5±0.8 kg/m²) were each studied on four occasions when they received an intraduodenal infusion of either (i) 0.9% saline or (ii) glucose delivered at a rate of 3 kcal/min both with, and without, an intragastric balloon with the pressure set to 8 mmHg above the intragastric minimum distending pressure. Results Following intraduodenal saline or glucose infusion, there was no difference in plasma GLP-1 with or without gastric distension (P=1.00 for both saline and glucose infusions). There was also no difference in plasma GIP with or without gastric distension (P=1.00 for saline infusion and P=0.99 for glucose infusion). Conclusion We conclude that gastric distension, either alone or during small intestinal glucose exposure, does not stimulate incretin hormone secretion significantly in healthy humans. This article is protected by copyright. All rights reserved.Ryan J. Jalleh, Laurence G. Trahair, Tongzhi Wu, Scott Standfield, Christine Feinle-Bisset, Christopher K. Rayner, Michael Horowitz, Karen L. Jone

Artificial sweeteners have no effect on gastric emptying, glucagon-like peptide-1, or glycemia after oral glucose in healthy humans

Tongzhi Wu, Michelle J. Bound, Scott D. Standfield, Max Bellon, Richard L. Young, Karen L. Jones, Michael Horowitz, and Christopher K. Rayne

Grass burning under our feet: Indigenous enterprise development in a political economy of whiteness

In this article we discuss some of our findings from two research projects that explore opportunities for Indigenous enterprise development in remote locations in Northern and Central Australia. Based on a series of focus groups and in-depth interviews with Indigenous community leaders, Traditional Owners, government officials, Land Council officials and other stakeholders, we discuss barriers to economic development faced by Indigenous communities in remote regions. We argue that many of these barriers are the material effects of discursive practices of ‘whiteness’ in the political economy. We discuss the relationships between institutions and Indigenous communities that constitute the Indigenous political economy and argue that these relationships are informed by discursive practices of whiteness and colonial-capitalist relations of power. We conclude by discussing the implications of our findings for management learning and public policy

Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial.

BACKGROUND: Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation. METHODS: The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25-100 nmol/L at 10-17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007-001716-23. FINDINGS: Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3-62·8] vs 60·5 g [59·3-61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related. INTERPRETATION: Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited. FUNDING: Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability