Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

AIMS: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes. MATERIALS AND METHODS: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up. RESULTS: Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035-1.531) p = 0.0213), albuminuria (OR 1.277 (1.124-1.454), p = 0.0002; HR 1.608 (1.208-2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p = 0.0068; HR 1.324 (1.089-1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p = 0.0109). CONCLUSIONS: Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.

Reliability, validity and acceptability of an online clinical reasoning simulator for medical students: An international pilot.

INTRODUCTION: Clinical reasoning skills are essential for decision-making. Current assessment methods are limited when testing clinical reasoning and management of uncertainty. This study evaluates the reliability, validity and acceptability of Practicum Script, an online simulation-based programme, for developing medical students' clinical reasoning skills using real-life cases. METHODS: In 2020, we conducted an international, multicentre pilot study using 20 clinical cases with 2457 final-year medical students from 21 schools worldwide. Psychometric analysis was performed (n = 1502 students completing at least 80% of cases). Classical estimates of reliability for three test domains (hypothesis generation, hypothesis argumentation and knowledge application) were calculated using Cronbach's alpha and McDonald's omega coefficients. Validity evidence was obtained by confirmatory factor analysis (CFA) and measurement alignment (MA). Items from the knowledge application domain were analysed using cognitive diagnostic modelling (CDM). Acceptability was evaluated by an anonymous student survey. RESULTS: Reliability estimates were high with narrow confidence intervals. CFA revealed acceptable goodness-of-fit indices for the proposed three-factor model. CDM analysis demonstrated good absolute test fit and high classification accuracy estimates. Student survey responses showed high levels of acceptability. CONCLUSION: Our findings suggest that Practicum Script is a useful resource for strengthening students' clinical reasoning skills and ability to manage uncertainty.

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.

Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry.

The Scientific Investigation Committee of the American Academy of Restorative Dentistry offers this review of the 2022 dental literature to briefly touch on several topics of interest to modern restorative dentistry. Each committee member brings discipline-specific expertise in their subject areas that include (in order of the appearance in this report): prosthodontics; periodontics, alveolar bone, and peri-implant tissues; dental materials and therapeutics; occlusion and temporomandibular disorders; sleep-related breathing disorders; oral medicine and oral and maxillofacial surgery; and dental caries and cariology. The authors focused their efforts on reporting information likely to influence the daily dental treatment decisions of the reader with an emphasis on innovations, new materials and processes, and future trends in dentistry. With the tremendous volume of literature published daily in dentistry and related disciplines, this review cannot be comprehensive. Instead, its purpose is to update interested readers and provide valuable resource material for those willing to subsequently pursue greater detail on their own. Our intent remains to assist colleagues in navigating the tremendous volume of newly minted information produced annually. Finally, we hope that readers find this work helpful in managing patients.

The acute effect of glucagon on components of energy balance and glucose homoeostasis in adults without diabetes: a systematic review and meta-analysis.

OBJECTIVE: Using a systematic review and meta-analysis, we aimed to estimate the mean effect of acute glucagon administration on components of energy balance and glucose homoeostasis in adults without diabetes. METHODS: CENTRAL, CINAHL, Embase, MEDLINE, PubMed, and Scopus databases were searched from inception to May 2021. To be included, papers had to be a randomised, crossover, single- or double-blind study, measuring ad libitum meal energy intake, energy expenditure, subjective appetite, glucose, and/or insulin following acute administration of glucagon and an appropriate comparator in adults without diabetes. Risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Randomized trials with additional considerations for cross-over trials. Certainty of evidence was assessed using the GRADE approach. Random-effect meta-analyses were performed for outcomes with at least five studies. This study is registered on PROSPERO (CRD42021269623). RESULTS: In total, 13 papers (15 studies) were considered eligible: energy intake (5 studies, 77 participants); energy expenditure (5 studies, 59 participants); subjective appetite (3 studies, 39 participants); glucose (13 studies, 159 participants); insulin (12 studies, 147 participants). All studies had some concerns with regards to risk of bias. Mean intervention effect of acute glucagon administration on energy intake was small (standardised mean difference [SMD]: -0.19; 95% CI, -0.59 to 0.21; P = 0.345). Mean intervention effect of acute glucagon administration on energy expenditure (SMD: 0.72; 95% CI, 0.37-1.08; P < 0.001), glucose (SMD: 1.11; 95% CI, 0.60-1.62; P < 0.001), and insulin (SMD: 1.33; 95% CI, 0.88-1.77; P < 0.001) was moderate to large. CONCLUSIONS: Acute glucagon administration produces substantial increases in energy expenditure, and in circulating insulin and glucose concentrations. However, the effect of acute glucagon administration on energy intake is unclear. Insufficient evidence was available to evaluate the acute effect of glucagon on subjective appetite.

The homeostatic dynamics of feeding behaviour identify novel mechanisms of anorectic agents.

Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analysing the different effects on feeding behaviour of peptide YY3-36 (PYY3-36), lithium chloride, glucagon-like peptide 1 (GLP-1), and leptin shows the precise behavioural changes caused by each anorectic agent. Our analysis demonstrates that the changes in feeding behaviour evoked by the anorectic agents investigated do not mimic the behaviour of well-fed animals and that the intermeal interval is influenced by fullness. We show how robust homeostatic control of feeding thwarts attempts to reduce food intake and how this might be overcome. In silico experiments suggest that introducing a minimum intermeal interval or modulating upper gut emptying can be as effective as anorectic drug administration.

BMAT's predictive validity for medical school performance: A retrospective cohort study.

BACKGROUND: Although used widely, there is limited evidence of the BioMedical Admissions Test's (BMAT) predictive validity and incremental validity over prior educational attainment (PEA). We investigated BMAT's predictive and incremental validity for performance in two undergraduate medical schools, Imperial College School of Medicine (ICSM), UK, and Lee Kong Chian School of Medicine (LKCMedicine), Singapore. Our secondary goal was to compare the evidence collected with published evidence relating to comparable tools. METHODS: This was a retrospective cohort study of four ICSM (1188 students, entering 2010-2013) and three LKCMedicine cohorts (222 students, 2013-2015). We investigated associations between BMAT Section 1 ('Thinking Skills'), Section 2 ('Scientific Knowledge and Applications') and Section 3a ('Writing Task') scores, with written and clinical assessment performance across all programme years. Incremental validity was investigated over PEA (A-levels) in a subset of ICSM students. RESULTS: When BMAT sections were investigated independently, Section 2 scores predicted performance on all written assessments in both institutions with mainly small effect sizes (standardised coefficient ranges: ICSM: 0.08-0.19; LKCMedicine: 0.22-0.36). Section 1 scores predicted Years 5 and 6 written assessment performance at ICSM (0.09-0.14) but nothing at LKCMedicine. Section 3a scores only predicted Year 5 clinical assessment performance at ICSM with a coefficient <0.1. There were no positive associations with standardised coefficients >0.1 between BMAT performance and clinical assessment performance. Multivariable regressions confirmed that Section 2 scores were the most predictive. We found no clear evidence of incremental validity for any BMAT section scores over A-level grades. DISCUSSION: Schools who wish to assess scientific knowledge independently of A-levels may find BMAT Section 2 useful. Comparison with previous studies indicates that, overall, BMAT seems less useful than comparable tools. Larger scale studies are needed. Broader questions regarding why institutions adopt certain admissions tests, including those with little evidence, need consideration.

Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry.

The Scientific Investigation Committee of the American Academy of Restorative Dentistry offers this review of the 2021 dental literature in restorative dentistry to inform busy dentists regarding noteworthy scientific and clinical progress over the past year. Each member of the committee brings discipline-specific expertise to coverage of this broad topical area. Specific subject areas addressed, in order of the appearance in this report, include COVID-19 and the dental profession (new); prosthodontics; periodontics, alveolar bone, and peri-implant tissues; implant dentistry; dental materials and therapeutics; occlusion and temporomandibular disorders; sleep-related breathing disorders; oral medicine and oral and maxillofacial surgery; and dental caries and cariology. The authors focused their efforts on reporting information likely to influence daily dental treatment decisions with an emphasis on future trends in dentistry. With the tremendous volume of dentistry and related literature being published daily, this review cannot possibly be comprehensive. Rather, its purpose is to update interested readers and provide important resource material for those interested in pursuing greater details on their own. It remains our intent to assist colleagues in negotiating the extensive volume of important information being published annually. It is our hope that readers find this work useful in successfully managing the patients and dental problems they encounter.

Differential effects of L- and D-phenylalanine on pancreatic and gastrointestinal hormone release in humans: A randomized crossover study.

AIM: To investigate the effects of L-phenylalanine on gastroenteropancreatic hormone release, glucose levels, subjective appetite and energy intake in humans, and to determine whether these effects were stereoisomer-specific by comparing them with D-phenylalanine. MATERIALS AND METHODS: A dose-finding, non-randomized, unblinded, crossover study was conducted during October-December 2017 at the NIHR Imperial Clinical Research Facility in five participants, in which the tolerability of escalating doses of oral L-phenylalanine was assessed (0, 3, 6 and 10 g). Also, an acute, randomized, double-blind, placebo-controlled crossover study was conducted during January-May 2018 at the NIHR Imperial Clinical Research Facility in 11 participants, in which the effects of oral 10 g L-phenylalanine relative to D-phenylalanine and placebo on gastroenteropancreatic hormone (insulin, glucagon, glucose-dependent insulinotropic polypeptide [GIP], peptide tyrosine tyrosine [PYY], glucagon-like peptide-1) and glucose concentrations, visual analogue scales for subjective appetite and energy intake at an ad libitum meal served 70 minutes postingestion, were investigated. RESULTS: L-phenylalanine was well-tolerated and increased insulin and glucagon concentrations prior to meal ingestion at several time points relative to placebo and D-phenylalanine (P < .05). L-phenylalanine also increased GIP concentrations relative to D-phenylalanine (P = .0420) and placebo (P = .0249) 70 minutes following ingestion. L-phenylalanine reduced postprandial glucose area under the curve (AUC)70-150mins relative to placebo (P = .0317) but did not affect subjective appetite or energy intake (P > .05). D-phenylalanine increased postprandial PYY AUC70-150mins concentrations relative to placebo (P = .0002). CONCLUSIONS: Ingestion of L-phenylalanine, but not D-phenylalanine, increases insulin, glucagon and GIP concentrations without appearing to have a marked effect on appetite.

Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry.

The Scientific Investigation Committee of the American Academy of Restorative Dentistry offers this review of the 2020 professional literature in restorative dentistry to inform busy dentists regarding noteworthy scientific and clinical progress over the past year. Each member of the committee brings discipline-specific expertise to this work to cover this broad topic. Specific subject areas addressed include prosthodontics; periodontics, alveolar bone, and peri-implant tissues; implant dentistry; dental materials and therapeutics; occlusion and temporomandibular disorders (TMDs); sleep-related breathing disorders; oral medicine and oral and maxillofacial surgery; and dental caries and cariology. The authors focused their efforts on reporting information likely to influence day-to-day dental treatment decisions with a keen eye on future trends in the profession. With the tremendous volume of dentistry and related literature being published today, this review cannot possibly be comprehensive. The purpose is to update interested readers and provide important resource material for those interested in pursuing greater detail. It remains our intent to assist colleagues in navigating the extensive volume of important information being published annually. It is our hope that readers find this work useful in successfully managing the dental patients they encounter.

The digital POIP concept: Preorthodontic implant placement.

OBJECTIVE: The aim of this report is to present an interdisciplinary treatment involving periodontics, orthodontics, dental implant placement, and prosthodontics with a fully digital dentistry approach. CLINICAL CONSIDERATIONS: The patient presented with an edentulous ridge on the area of the lower left lateral incisor as well as gingival recession on the adjacent teeth. After performing a digital orthodontic setup and indirect bonding bracket placement, a dental implant placement was carried out before orthodontic treatment in combination with guided bone regeneration (GBR), connective tissue graft (CTG) and periodontal accelerated osteogenic orthodontics (PAOO). In a 6-month period, orthodontic treatment was fully completed and the dental implant was restored at 8 months. Following one-and-a-half years, significant gingival recession reduction was accomplished and soft tissue augmentation around the dental implant appeared stable with a good functional and esthetic result. CONCLUSION: The use of the digital POIP concept with a proper diagnosis and careful planning is crucial for reducing treatment time and enhancing precision.

Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry.

This comprehensive review of the 2019 restorative dental literature is offered to inform busy dentists regarding remarkable publications and noteworthy progress made in the profession. Developed by the Scientific Investigation Committee of the American Academy of Restorative Dentistry, each author brings discipline-specific expertise to 1 of 8 sections of the report: (1) prosthodontics; (2) periodontics, alveolar bone, and peri-implant tissues; (3) implant dentistry; (4) dental materials and therapeutics; (5) occlusion and temporomandibular disorders; (6) sleep-related breathing disorders; (7) oral medicine and oral and maxillofacial surgery; and (8) dental caries and cariology. The report targets important information likely to influence day-to-day dental treatment decisions. Each review is not intended to stand alone but to update interested readers so that they may visit source material when greater detail is desired. As the profession moves toward evidence-based clinical decision-making, an incredible volume of potentially valuable dental literature continues to increase. It is the intention of this review and its authors to provide assistance in negotiating the extensive dental literature published in 2019. It is our hope that readers find this work useful in the clinical management of dental patients.

Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.

OBJECTIVE: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. DESIGN: Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. RESULTS: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. CONCLUSION: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.

OBJECTIVE: The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. DESIGN: To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. RESULTS: Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. CONCLUSIONS: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. TRIAL REGISTRATION NUMBER: NCT00750438.

Detailed characterization of a long-term rodent model of critical illness and recovery.

OBJECTIVE: To characterize a long-term model of recovery from critical illness, with particular emphasis on cardiorespiratory, metabolic, and muscle function. DESIGN: Randomized controlled animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Intraperitoneal injection of the fungal cell wall constituent, zymosan or n-saline. MEASUREMENTS AND MAIN RESULTS: Following intervention, rats were followed for up to 2 weeks. Animals with zymosan peritonitis reached a clinical and biochemical nadir on day 2. Initial reductions were seen in body weight, total body protein and fat, and muscle mass. Leg muscle fiber diameter remained subnormal at 14 days with evidence of persisting myonecrosis, even though gene expression of regulators of muscle mass (e.g., MAFbx, MURF1, and myostatin) had peaked on days 2-4 but normalized by day 7. Treadmill exercise capacity, forelimb grip strength, and in vivo maximum tetanic force were also reduced. Food intake was minimal until day 4 but increased thereafter. This did not relate to appetite hormone levels with early (6 hr) rises in plasma insulin and leptin followed by persisting subnormal levels; ghrelin levels did not change. Serum interleukin-6 level peaked at 6 hours but had normalized by day 2, whereas interleukin-10 remained persistently elevated and high-density lipoprotein cholesterol persistently depressed. There was an early myocardial depression and rise in core temperature, yet reduced oxygen consumption and respiratory exchange ratio with a loss of diurnal rhythmicity that showed a gradual but incomplete recovery by day 7. CONCLUSIONS: This detailed physiological, metabolic, hormonal, functional, and histological muscle characterization of a model of critical illness and recovery reproduces many of the findings reported in human critical illness. It can be used to assess putative therapies that may attenuate loss, or enhance recovery, of muscle mass and function.

Cannabinoid concentrations detected in fatal road traffic collision victims compared with a population of other postmortem cases.

BACKGROUND: Acute cannabis consumption nearly doubles the risk of motor vehicle collision resulting in injury or death. Limited data have been published regarding the concentrations of cannabinoids associated with fatal road traffic collisions (RTCs), and these have not previously been compared to a population of other postmortem cases. METHODS: We conducted analysis for cannabinoids [Δ(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-THC-9-carboxylic acid, cannabidiol, and cannabinol], drugs, and alcohol on consecutive fatal RTC cases (100) and non-RTC cases (114) from coroners' jurisdictions in London and southeast England and compared the data. RESULTS: The incidence of cannabinoids detected in non-RTC and RTC cases was similar (25% vs 21%, P = 0.44), but THC was detected more frequently (90% vs 59%, P = 0.01) and at significantly higher concentrations in the cannabinoid-positive RTC cases than the non-RTC cases (P = 0.01). The distribution of non-RTC and RTC cases over 4 categories of THC concentration was significantly different (P = 0.004). There was no significant difference in the concentrations of other cannabinoids detected between the 2 groups. Cannabinoids were detected in more fatal RTC cases (21) than alcohol >80 mg/dL (17). Detection of other drugs was low compared to cannabis and alcohol. CONCLUSIONS: These first data on the concentrations of cannabinoids in the postmortem blood of fatal RTC victims compared with a population of other routine coroners' cases highlight the importance of specifically measuring THC concentrations in the blood to aid interpretation of postmortem cases where cannabis may be implicated.

Energy expenditure, nutritional status, body composition and physical fitness of Royal Marines during a 6-month operational deployment in Afghanistan.

Understanding the nutritional demands on serving military personnel is critical to inform training schedules and dietary provision. Troops deployed to Afghanistan face austere living and working environments. Observations from the military and those reported in the British and US media indicated possible physical degradation of personnel deployed to Afghanistan. Therefore, the present study aimed to investigate the changes in body composition and nutritional status of military personnel deployed to Afghanistan and how these were related to physical fitness. In a cohort of British Royal Marines (n 249) deployed to Afghanistan for 6 months, body size and body composition were estimated from body mass, height, girth and skinfold measurements. Energy intake (EI) was estimated from food diaries and energy expenditure measured using the doubly labelled water method in a representative subgroup. Strength and aerobic fitness were assessed. The mean body mass of volunteers decreased over the first half of the deployment ( - 4·6 (sd 3·7) %), predominately reflecting fat loss. Body mass partially recovered (mean +2·2 (sd 2·9) %) between the mid- and post-deployment periods (P< 0·05). Daily EI (mean 10 590 (sd 3339) kJ) was significantly lower than the estimated daily energy expenditure (mean 15 167 (sd 1883) kJ) measured in a subgroup of volunteers. However, despite the body mass loss, aerobic fitness and strength were well maintained. Nutritional provision for British military personnel in Afghanistan appeared sufficient to maintain physical capability and micronutrient status, but providing appropriate nutrition in harsh operational environments must remain a priority.

The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake.

Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.

Diet shapes the metabolite profile in the intact human ileum, which affects PYY release.

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites, and appetite hormone release remains unclear owing to limited access to intact human ileum. In a randomized crossover trial (ISRCTN11327221; isrctn.com), we investigated the role of human ileum in GLP-1 and PYY release by giving healthy volunteers diets differing in fiber and food structure: high-fiber (intact or disrupted food structures) or low-fiber disrupted food structures. We used nasoenteric tubes to sample chyme from the intact distal ileum lumina of humans in the fasted state and every 60 min for 480 min postprandially. We demonstrate the highly dynamic, wide-ranging molecular environment of the ileum over time, with a substantial decrease in ileum bacterial numbers and bacterial metabolites after food intake. We also show that high-fiber diets, independent of food structure, increased PYY release compared with a low-fiber diet during 0 to 240 min postprandially. High-fiber diets also increased ileal stachyose, and a disrupted high-fiber diet increased certain ileal amino acids. Treatment of human ileal organoids with ileal fluids or an amino acid and stachyose mixture stimulated PYY expression in a similar profile to blood PYY concentrations, confirming the role of ileal metabolites in PYY release. Our study demonstrates the diet-induced changes over time in the metabolite environment of intact human ileum, which play a role in PYY release.