Do high-protein diets have the potential to reduce gut barrier function in a sex-dependent manner?

PURPOSE: Impaired gut barrier function is associated with systemic inflammation and many chronic diseases. Undigested dietary proteins are fermented in the colon by the gut microbiota which produces nitrogenous metabolites shown to reduce barrier function in vitro. With growing evidence of sex-based differences in gut microbiotas, we determined whether there were sex by dietary protein interactions which could differentially impact barrier function via microbiota modification. METHODS: Fermentation systems were inoculated with faeces from healthy males (n = 5) and females (n = 5) and supplemented with 0.9 g of non-hydrolysed proteins sourced from whey, fish, milk, soya, egg, pea, or mycoprotein. Microbial populations were quantified using fluorescence in situ hybridisation with flow cytometry. Metabolite concentrations were analysed using gas chromatography, solid phase microextraction coupled with gas chromatography-mass spectrometry and ELISA. RESULTS: Increased protein availability resulted in increased proteolytic Bacteroides spp (p < 0.01) and Clostridium coccoides (p < 0.01), along with increased phenol (p < 0.01), p-cresol (p < 0.01), indole (p = 0.018) and ammonia (p < 0.01), varying by protein type. Counts of Clostridium cluster IX (p = 0.03) and concentration of p-cresol (p = 0.025) increased in males, while females produced more ammonia (p = 0.02), irrespective of protein type. Further, we observed significant sex-protein interactions affecting bacterial populations and metabolites (p < 0.005). CONCLUSIONS: Our findings suggest that protein fermentation by the gut microbiota in vitro is influenced by both protein source and the donor's sex. Should these results be confirmed through human studies, they could have major implications for developing dietary recommendations tailored by sex to prevent chronic illnesses.

Impact of a food-based dietary fat exchange model for replacing dietary saturated with unsaturated fatty acids in healthy men on plasma phospholipids fatty acid profiles and dietary patterns.

PURPOSE: UK guidelines recommend dietary saturated fatty acids (SFAs) should not exceed 10% total energy (%TE) for cardiovascular disease prevention, with benefits observed when SFAs are replaced with unsaturated fatty acids (UFAs). This study aimed to assess the efficacy of a dietary exchange model using commercially available foods to replace SFAs with UFAs. METHODS: Healthy men (n = 109, age 48, SD 11 year) recruited to the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention-1 (RISSCI-1) study (ClinicalTrials.Gov n°NCT03270527) followed two sequential 4-week isoenergetic moderate-fat (34%TE) diets: high-SFA (18%TE SFAs, 16%TE UFAs) and low-SFA (10%TE SFAs, 24%TE UFAs). Dietary intakes were assessed using 4-day weighed diet diaries. Nutrient intakes were analysed using paired t-tests, fasting plasma phospholipid fatty acid (PL-FA) profiles and dietary patterns were analysed using orthogonal partial least square discriminant analyses. RESULTS: Participants exchanged 10.2%TE (SD 4.1) SFAs for 9.7%TE (SD 3.9) UFAs between the high and low-SFA diets, reaching target intakes with minimal effect on other nutrients or energy intakes. Analyses of dietary patterns confirmed successful incorporation of recommended foods from commercially available sources (e.g. dairy products, snacks, oils, and fats), without affecting participants' overall dietary intakes. Analyses of plasma PL-FAs indicated good compliance to the dietary intervention and foods of varying SFA content. CONCLUSIONS: RISSCI-1 dietary exchange model successfully replaced dietary SFAs with UFAs in free-living healthy men using commercially available foods, and without altering their dietary patterns. Further intervention studies are required to confirm utility and feasibility of such food-based dietary fat replacement models at a population level.

Reducing postprandial glucose in dietary intervention studies and the magnitude of the effect on diabetes-related risk factors: a systematic review and meta-analysis.

PURPOSE: Reducing postprandial hyperglycemia has beneficial effects on diabetes-related risk factors, but the magnitude of the reduction needed to achieve such an effect is unknown. The purpose of the study was to quantify the relationship of acute glucose and insulin postprandial responses with longer-term effects on diabetes-related risk factors by performing a systematic review and meta-analysis of dietary intervention studies. METHODS: We systematically searched EMBASE and MEDLINE. Dietary intervention studies among any human population aiming to reduce postprandial glycemia, with actual measures of postprandial glucose (PPG) and/or insulin (PPI) as acute exposures (incremental area under the curve, iAUC) as well as markers of glucose metabolism (fasting glucose, HbA1c) and insulin sensitivity (fasting insulin, HOMA-IR) after at least 4 weeks of diet intervention as outcomes were included. Meta-analyses were performed for the effects on acute exposures and on diabetes-related risk factors. The relationship between changes in acute exposures and changes in risk factor outcomes was estimated by meta-regression analyses. RESULTS: Out of the 13,004 screened papers, 13 papers with 14 comparisons were included in the quantitative analysis. The dietary interventions acutely reduced mean PPG [mean difference (MD), - 0.27 mmol/l; 95% CI - 0.41 to - 0.14], but not mean PPI (MD - 7.47 pmol/l; 95% CI - 16.79 to 1.86). There were no significant overall effects on fasting glucose and insulin. HbA1c was reduced by - 0.20% (95% CI - 0.35 to - 0.05). Changes in acute PPG were significantly associated with changes in fasting plasma glucose (FPG) [per 10% change in PPG: ß = 0.085 (95% CI 0.003, 0.167), k = 14], but not with fasting insulin [ß = 1.20 (95% CI - 0.32, 2.71), k = 12]. Changes in acute PPI were not associated with changes in FPG [per 10% change in PPI: ß = - 0.017 (95% CI - 0.056, 0.022), k = 11]. CONCLUSIONS: Only a limited number of postprandial glucose-lowering dietary intervention studies measured acute postprandial exposures to PPG/PPI during the interventions. In this small heterogeneous set of studies, an association was found between the magnitude of the acute postprandial responses and the change in fasting glucose, but no other outcomes. More studies are needed to quantify the relationship between acute postprandial changes and long-term effects on risk factors.

Association between vitamin D and glycaemic parameters in a multi-ethnic cohort of postmenopausal women with type 2 diabetes in Saudi Arabia.

BACKGROUND: The relationship between vitamin D (VitD) and insulin sensitivity and secretion in type 2 diabetes mellitus (T2D) has been shown to be different amongst different ethnic populations. In Saudi Arabia, where both T2D and VitD deficiency are highly prevalent health concerns, little is known about the relationship between VitD, insulin sensitivity, resistance and the relative importance of ethnicity. Our primary aim in this study was to investigate influence of ethnicity on VitD association with glycaemic profile and to measures of obesity as a secondary outcome, among multiethnic postmenopausal women with T2D in Saudi Arabia. METHODS: A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Postmenopausal females (n = 173, age ≥ 50 years) with T2D were randomly selected in this study. Anthropometric measures and fasting blood samples were obtained for all study participants. Several biochemical parameters were measured including 25-hydroxyvitamin D (25(OH)D), glycosylated hemoglobin (HbA1c), insulin, glucose and c-peptide. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment 2 for insulin resistance and beta cell activity (HOMA2-IR, HOMA2-ß). RESULTS: Overall, 25(OH)D was inversely associated with fasting glucose (r=-0.165, P = 0.037), insulin (r=-0.184, P = 0.02), C-peptide (r=-0.19, P = 0.015) and HOMA2- IR C-peptide (r=-0.23, P = 0.004). Additionally, serum 25 (OH)D showed a negative correlation with body weight (r=-0.173 P = 0.028), waist and hip circumferences (r=-0.167, P = 0.033; r=-0.22, P = 0.004 respectively) but not with body mass index (BMI) or waist hip ratio (WHR). In the white ethnic group but not in black or Asian population groups, 25(OH)D level was also associated with only serum fasting C-peptide and HOMA2-IR C-peptide and BMI (P < 0.05). CONCLUSIONS: Insulin resistance and obesity were associated with VitD status in T2D in this cohort. Our findings also suggest that these VitD associations in women from white ethnic background are different than in those from black/Asian ethnic backgrounds. Whether VitD supplements are able to improve either obesity and/or insulin sensitivity should be further investigated in different ethnic population groups.

Identification of factors influencing motivation to undertake time-restricted feeding in humans.

The interaction between time of day and energy intake, termed chrono-nutrition, has received considerable recent interest. One aspect of chrono-nutrition with potential to benefit long-term cardio-metabolic health is time-restricted feeding (TRF). Current support for TRF primarily derives from animal research, although recent small-scale human studies indicate possible translational benefit. Whether free-living humans, however, can incorporate TRF into their daily lives is poorly understood. This study reports data from participants (n = 608) who completed an online questionnaire to investigate daily routine, likelihood of TRF incorporation within work vs free-days, and key considerations influencing TRF uptake. The majority of participants reported a typical daily feeding window (time between first and last energy intake) of between 10 and 14 h on workdays and free days, 62.7 and 65.5% respectively. Likelihood of adherence to TRF declined with an increase in the proposed restriction of the feeding window by 0.5 to 4-h per day. We then examined data from participants with a typical daily feeding window of 12+ h on workdays (n = 221) and free-days (n = 223) to investigate the likelihood of using TRF, and the most important considerations in making this decision. Of these participants, (n = 132) on workdays and (n = 125) on free days would likely reduce their feeding window by 3-h. Multiple regression analysis revealed that key considerations determining the likelihood of adopting TRF were: cost, time availability, and perceived health benefits (on workdays); wake time, bed time, time availability, motivation to change and perceived health benefits (on free-days). These data provide novel information regarding public attitudes towards TRF and highlight important aspects to be considered when translating controlled laboratory studies to public dietary advice.

Intermittent v. continuous energy restriction: differential effects on postprandial glucose and lipid metabolism following matched weight loss in overweight/obese participants.

The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (>70 %) energy restriction (ER) interspersed with normal eating. Studies to date comparing IER to continuous energy restriction (CER) have predominantly measured fasting indices of cardiometabolic risk. This study aimed to compare the effects of IER and CER on postprandial glucose and lipid metabolism following matched weight loss. In all, twenty-seven (thirteen male) overweight/obese participants (46 (sem 3) years, 30·1 (sem 1·0) kg/m2) who were randomised to either an IER intervention (2638 kJ for 2 d/week with an overall ER of 22 (sem 0·3) %, n 15) or a CER intervention (2510 kJ below requirements with overall ER of 23 (sem 0·8) %) completed the study. Postprandial responses to a test meal (over 360 min) and changes in anthropometry (fat mass, fat-free mass, circumferences) were assessed at baseline and upon attainment of 5 % weight loss, following a 7-d period of weight stabilisation. The study found no statistically significant difference in the time to attain a 5 % weight loss between groups (median 59 d (interquartile range (IQR) 41-80) and 73 d (IQR 48-128), respectively, P=0·246), or in body composition (P≥0·437). For postprandial measures, neither diet significantly altered glycaemia (P=0·266), whereas insulinaemia was reduced comparatively (P=0·903). The reduction in C-peptide tended (P=0·057) to be greater following IER (309 128 (sem23 268) to 247781 (sem20 709) pmol×360 min/l) v. CER (297 204 (sem25 112) to 301 655 (sem32 714) pmol×360 min/l). The relative reduction in TAG responses was greater (P=0·045) following IER (106 (sem30) to 68 (sem 15) mmol×360 min/l) compared with CER (117 (sem 43) to 130 (sem 31) mmol×360 min/l). In conclusion, these preliminary findings highlight underlying differences between IER and CER, including a superiority of IER in reducing postprandial lipaemia, which now warrant targeted mechanistic evaluation within larger study cohorts.

Postprandial glycaemic and lipaemic responses to chronic coffee consumption may be modulated by CYP1A2 polymorphisms.

There is much epidemiological evidence suggesting a reduced risk of development of type 2 diabetes (T2D) in habitual coffee drinkers, however to date there have been few longer-term interventions, directly examining the effects of coffee intake on glucose and lipid metabolism. Previous studies may be confounded by inter-individual variation in caffeine metabolism. Specifically, the rs762551 SNP in the CYP1A2 gene has been demonstrated to influence caffeine metabolism, with carriers of the C allele considered to be of a 'slow' metaboliser phenotype. This study investigated the effects of regular coffee intake on markers of glucose and lipid metabolism in coffee-naïve individuals, with novel analysis by rs762551 genotype. Participants were randomised to either a coffee group (n 19) who consumed four cups/d instant coffee for 12 weeks or a control group (n 8) who remained coffee/caffeine free. Venous blood samples were taken pre- and post-intervention. Primary analysis revealed no significant differences between groups. Analysis of the coffee group by genotype revealed several differences. Before coffee intake, the AC genotype ('slow' caffeine metabolisers, n 9) displayed higher baseline glucose and NEFA than the AA genotype ('fast' caffeine metabolisers, n 10, P<0·05). Post-intervention, reduced postprandial glycaemia and reduced NEFA suppression were observed in the AC genotype, with the opposite result observed in the AA genotype (P<0·05). These observed differences between genotypes warrant further investigation and indicate there may be no one-size-fits-all recommendation with regard to coffee drinking and T2D risk.

Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants.

The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (75-100 %) energy restriction (ER) interspersed with normal eating. This study aimed to characterise the early metabolic response to these varying degrees of ER, which occurs acutely and prior to weight loss. Ten (three female) healthy, overweight/obese participants (36 (SEM 5) years; 29·0 (sem 1·1) kg/m2) took part in this acute three-way cross-over study. Participants completed three 1-d dietary interventions in a randomised order with a 1-week washout period: isoenergetic intake, partial 75 % ER and total 100 % ER. Fasting and postprandial (6-h) metabolic responses to a liquid test meal were assessed the following morning via serial blood sampling and indirect calorimetry. Food intake was also recorded for two subsequent days of ad libitum intake. Relative to the isoenergetic control, postprandial glucose responses were increased following total ER (+142 %; P=0·015) and to a lesser extent after partial ER (+76 %; P=0·051). There was also a delay in the glucose time to peak after total ER only (P=0·024). Both total and partial ER interventions produced comparable reductions in postprandial TAG responses (-75 and -59 %, respectively; both P<0·05) and 3-d energy intake deficits of approximately 30 % (both P=0·015). Resting and meal-induced thermogenesis were not significantly affected by either ER intervention. In conclusion, our data demonstrate the ability of substantial ER to acutely alter postprandial glucose-lipid metabolism (with partial ER producing the more favourable overall response), as well as incomplete energy-intake compensation amongst overweight/obese participants. Further investigations are required to establish how metabolism adapts over time to the repeated perturbations experienced during IER, as well as the implications for long-term health.

Host-microbiome interactions in human type 2 diabetes following prebiotic fibre (galacto-oligosaccharide) intake.

Aberrant microbiota composition and function have been linked to several pathologies, including type 2 diabetes. In animal models, prebiotics induce favourable changes in the intestinal microbiota, intestinal permeability (IP) and endotoxaemia, which are linked to concurrent improvement in glucose tolerance. This is the first study to investigate the link between IP, glucose tolerance and intestinal bacteria in human type 2 diabetes. In all, twenty-nine men with well-controlled type 2 diabetes were randomised to a prebiotic (galacto-oligosaccharide mixture) or placebo (maltodextrin) supplement (5·5 g/d for 12 weeks). Intestinal microbial community structure, IP, endotoxaemia, inflammatory markers and glucose tolerance were assessed at baseline and post intervention. IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin-modified intravenous glucose tolerance test. Intestinal microbial community analysis was performed by high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR. Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo; however, changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels (r -0·90, P=0·042 for both) following prebiotic intake. The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding. We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role. The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes.

L-rhamnose as a source of colonic propionate inhibits insulin secretion but does not influence measures of appetite or food intake.

Activation of free fatty acid receptor (FFAR)2 and FFAR3 via colonic short-chain fatty acids, particularly propionate, are postulated to explain observed inverse associations between dietary fiber intake and body weight. Propionate is reported as the predominant colonic fermentation product from l-rhamnose, a natural monosaccharide that resists digestion and absorption reaching the colon intact, while effects of long-chain inulin on appetite have not been extensively investigated. In this single-blind randomized crossover study, healthy unrestrained eaters (n = 13) ingested 25.5 g/d l-rhamnose, 22.4 g/d inulin or no supplement (control) alongside a standardized breakfast and lunch, following a 6-d run-in to investigate if appetite was inhibited. Postprandial qualitative appetite, breath hydrogen, and plasma glucose, insulin, triglycerides and non-esterified fatty acids were assessed for 420 min, then an ad libitum meal was provided. Significant treatment x time effects were found for postprandial insulin (P = 0.009) and non-esterified fatty acids (P = 0.046) with a significantly lower insulin response for l-rhamnose (P = 0.023) than control. No differences between treatments were found for quantitative and qualitative appetite measures, although significant treatment x time effects for meal desire (P = 0.008) and desire to eat sweet (P = 0.036) were found. Breath hydrogen was significantly higher with inulin (P = 0.001) and l-rhamnose (P = 0.009) than control, indicating colonic fermentation. These findings suggest l-rhamnose may inhibit postprandial insulin secretion, however neither l-rhamnose or inulin influenced appetite.

A single serving of caffeinated coffee impairs postprandial glucose metabolism in overweight men.

UNLABELLED: Previous studies regarding the acute effects of coffee on glycaemic control have used a single large dose of coffee, typically containing the caffeine equivalent of 2-4 servings of coffee. This study investigates whether the acute effects of coffee are dose-dependent, starting with a single serving. A total of ten healthy overweight males participated in a two-part randomised double-blind cross-over study. In the first part, they ingested 2, 4 or 8 g instant decaffeinated coffee (DC) dissolved in 400 ml water with caffeine added in proportion to the DC (total 100, 200 or 400 mg caffeine) or control (400 ml water) all with 50 g glucose. In the second part, they ingested the same amounts of DC (2, 4, 8 g) or control, but with a standard 100 mg caffeine added to each. Capillary blood samples were taken every 15 min for 2 h after each drink and glucose and insulin levels were measured. Repeated measures ANOVA on glucose results found an effect when caffeine was varied in line with DC (P=0·008). Post hoc analysis revealed that both 2 and 4 g DC with varied caffeine content increased the glycaemic response v. CONTROL: There was no effect of escalating doses of DC when caffeine remained constant at 100 mg. These results demonstrate that one standard serving of coffee (2 g) is sufficient to affect glucose metabolism. Furthermore, the amount of caffeine found in one serving (100 mg) is sufficient to mask any potential beneficial effects of increasing other components. No dose-dependent effect was found.

Standard Nutritional Assessment Tools Are Unable to Predict Loss of Muscle Mass in Patients Due to Undergo Pancreatico-Duodenectomy: Highlighting the Need for Detailed Nutritional Assessment.

BACKGROUND AND METHODS: Pancreatico-duodenectomy (PD) carries significant morbidity and mortality, with very few modifiable risk factors. Radiological evidence of sarcopenia is associated with poor outcomes. This retrospective study aimed to analyse the relationship between easy-to-use bedside nutritional assessment techniques and radiological markers of muscle loss to identify those patients most likely to benefit from prehabilitation. RESULTS: Data were available in 184 consecutive patients undergoing PD. Malnutrition was present in 33-71%, and 48% had a high visceral fat-to-skeletal muscle ratio, suggestive of sarcopenic obesity (SO). Surgical risk was higher in patients with obesity (OR 1.07, 95%CI 1.01-1.14, p = 0.031), and length of stay was 5 days longer in those with SO (p = 0.006). There was no correlation between skeletal muscle and malnutrition using percentage weight loss or the malnutrition universal screening tool (MUST), but a weak correlation between the highest hand grip strength (HGS; 0.468, p < 0.001) and the Global Leadership in Malnutrition (GLIM) criteria (-0.379, p < 0.001). CONCLUSIONS: Nutritional assessment tools give widely variable results. Further research is needed to identify patients at significant nutritional risk prior to PD. In the meantime, those with malnutrition (according to the GLIM criteria), obesity or low HGS should be referred to prehabilitation.

Variation of LDL-cholesterol in response to the replacement of saturated with unsaturated fatty acids: a non-randomised, sequential dietary intervention study (RISSCI-1).

BACKGROUND: Serum LDL-cholesterol (LDL-C) shows marked inter-individual variation in response to replacement of saturated fatty acids (SFA) with unsaturated fatty acids (UFA). OBJECTIVE: To demonstrate the efficacy of UK guidelines for exchanging dietary SFA for UFA, to reduce serum LDL-C and other CVD risk factors, and to identify determinants of the variability in LDL-C response. METHODS: Healthy males (n=109, mean±SD age 48±11 years BMI 25.1±3.3 kg/m2), consumed a higher-SFA/lower-UFA diet for 4-weeks, followed by an isoenergetic, lower-SFA/higher-UFA diet for 4-weeks (achieved intakes SFA:UFA, 19.1:14.8 and 8.9:24.5% total energy respectively). Serum LDL-C, CVD risk markers, peripheral blood mononuclear cell (PBMC) gene expression, and dietary intakes were assessed at baseline and the end of each diet. RESULTS: Transition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet significantly reduced fasting blood lipids [LDL-C (-0.50 mmol/L; 95%CI:-0.58,-0.42), HDL-C (-0.11 mmol/L; 95%CI:-0.14,-0.08) and total cholesterol (-0.65 mmol/L; 95%CI:-0.75,-0.55)]. The dietary exchange also reduced apolipoprotein (apo)B, TC:HDL-C ratio, non-HDL-C, E-selectin (P<0.0001) and LDL subfraction composition [cholesterol (LDL-I and LDL-II), apoB100 (LDL-I and LDL-II), and TAG (LDL-II)] (P<0.01). There was also an increase in plasma biomarkers of cholesterol intestinal absorption (ß-sitosterol, campesterol, cholestanol), and synthesis (desmosterol) (P<0.0001) and fold change in PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet (P=0.035). Marked inter-individual variation in the change in serum LDL-C response (-1.39 to +0.77 mmol/L) to this dietary exchange was observed, with 33.7% of this variation explained by serum LDL-C before the lower-SFA/higher-UFA diet and reduction in dietary SFA intake (adjusted R2 27% and 6.7%, respectively). APOE genotype was unrelated to serum LDL-C response to SFA. CONCLUSIONS: These findings support the efficacy of UK SFA dietary guidelines for the overall lowering of serum LDL-C, but showed marked variation in LDL-C response. Further identification of the determinants of this variation will facilitate targeting and increasing efficacy of these guidelines. CLINICAL TRIAL REGISTRY: The RISSCI-1 study was registered with ClinicalTrials.Gov (No. NCT03270527).

Endogenous plasma glucagon-like peptide-1 following acute dietary fibre consumption.

SCFA resulting from the microbial fermentation of carbohydrates have been linked to increased glucagon-like peptide-1 (GLP-1) secretion from the gastrointestinal tract in cell and animal models; however, there is little direct evidence in human subjects to confirm this. The present study was designed to investigate whether endogenous plasma GLP-1 concentrations increase following acute consumption of 48 g dietary fibre (as resistant starch (RS) from high-amylose maize type 2 RS (HAM-RS2)) compared with a matched placebo. A total of thirty healthy males participated in the present randomised cross-over study where HAM-RS2 or placebo was consumed as part of standardised breakfast and lunch meals. Changes to GLP-1, glucose, insulin and C-peptide were assessed half hourly for 7 h. Following the breakfast meal, plasma GLP-1 concentrations were lower with HAM-RS2 compared with the placebo (P = 0·025). However, there was no significant difference between the supplements following the lunch meal. Plasma insulin concentrations were significantly lower following the lunch meal (P = 0·034) with HAM-RS2 than with the placebo, but were not different after breakfast. Plasma glucose and C-peptide concentrations did not differ at any point. These results suggest that increased dietary fibre intake, in the form of HAM-RS2, does not acutely increase endogenous GLP-1 concentrations in human subjects. Further fibre feeding studies are required to determine whether GLP-1 concentrations may increase following longer-term consumption.

Do Patients Benefit from Micronutrient Supplementation following Pancreatico-Duodenectomy?

Pancreatico-duodenectomy (PD) includes resection of the duodenum and use of the proximal jejunum in a blind loop, thus reducing the absorptive capacity for vitamins and minerals. Several studies have analysed the frequency of micronutrient deficiencies, but there is a paucity of data on those taking routine supplements. A retrospective review of medical notes was undertaken on 548 patients under long-term follow-up following PD in a tertiary hepato-pancreatico-biliary centre. Data were available on 205 patients from 1-14 years following PD, and deficiencies were identified as follows: vitamin A (3%), vitamin D (46%), vitamin E (2%), iron (42%), iron-deficiency anaemia (21%), selenium (3%), magnesium (6%), copper (1%), and zinc (44%). Elevated parathyroid hormone was present in 11% of cases. There was no significant difference over time (p > 0.05). Routine supplementation with a vitamin and mineral supplement did appear to reduce the incidence of biochemical deficiency in vitamin A, vitamin E, and selenium compared to published data. However, iron, vitamin D, and zinc deficiencies were prevalent despite supplementation and require surveillance.

Daily rhythms of diabetogenic factors in men: role of type 2 diabetes and body weight.

Obesity is a major cause of type 2 diabetes. Transition from obesity to type 2 diabetes manifests in the dysregulation of hormones controlling glucose homeostasis and inflammation. As metabolism is a dynamic process that changes across 24 h, we assessed diurnal rhythmicity in a panel of 10 diabetes-related hormones. Plasma hormones were analysed every 2 h over 24 h in a controlled laboratory study with hourly isocaloric drinks during wake. To separate effects of body mass from type 2 diabetes, we recruited three groups of middle-aged men: an overweight (OW) group with type 2 diabetes and two control groups (lean and OW). Average daily concentrations of glucose, triacylglycerol and all the hormones except visfatin were significantly higher in the OW group compared to the lean group (P < 0.001). In type 2 diabetes, glucose, insulin, C-peptide, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 increased further (P < 0.05), whereas triacylglycerol, ghrelin and plasminogen activator inhibitor-1 concentrations were significantly lower compared to the OW group (P < 0.001). Insulin, C-peptide, glucose-dependent insulinotropic peptide and leptin exhibited significant diurnal rhythms in all study groups (P < 0.05). Other hormones were only rhythmic in 1 or 2 groups. In every group, hormones associated with glucose regulation (insulin, C-peptide, glucose-dependent insulinotropic peptide, ghrelin and plasminogen activator inhibitor-1), triacylglycerol and glucose peaked in the afternoon, whereas glucagon and hormones associated with appetite and inflammation peaked at night. Thus being OW with or without type 2 diabetes significantly affected hormone concentrations but did not affect the timing of the hormonal rhythms.

Exploring Rates of Adherence and Barriers to Time-Restricted Eating.

Whilst the treatment and prevention of overweight and obesity-related disease is managed by restricting daily energy intake, long-term adherence to dietary strategies appears unsustainable. Time-restricted eating (TRE) aims to position energy intake in an eating window under 12 h per day and offers an alternative behavioral intervention, which can aid weight management and improve cardiometabolic health. Adherence to previous TRE protocols is estimated at between 63 and 100%, although the accuracy of reporting is unclear. This study therefore aimed to provide an objective, subjective, and qualitative overview of adherence to a prescribed TRE protocol, and to identify any potential barriers affecting adherence. Adherence after 5 weeks of TRE was estimated at ~63% based on continuous glucose monitoring data when compared with time-stamped diet diaries. Subjective participant responses reported adherence at an average of ~61% per week. Barriers to adopting TRE, including work schedules, social events, and family life, were identified by participants during qualitative interviews. The findings of this study suggest that the development of personalized TRE protocols may help to navigate the barriers to adherence leading to improved health-related outcomes.

Dietary-resistant starch and glucose metabolism.

PURPOSE OF REVIEW: Recent findings in animal models suggest that resistant starch is beneficial for both body weight regulation and glycaemic control. The purpose of this review is to summarize the current evidence and recommendations in humans. RECENT FINDINGS: When resistant starch replaces available carbohydrate in a meal, postprandial glycaemia is reduced. There are some data to suggest that resistant starch may affect glycaemia even when the available carbohydrate portion remains constant; however, there is inconsistency in the literature. Recent animal data suggest that chronic resistant starch feeding upregulates glucagon-like peptide 1 expression in the large bowel with concomitant increases in neuropeptide expression in the hypothalamus, combining to result in weight loss and improvements in glycaemic control. However, to date there is no evidence for this in humans. SUMMARY: Resistant starch may have a role in glycaemic control in healthy individuals and those with type 2 diabetes; however, there are limited interventional trials in humans to support this. There are no data concerning resistant starch feeding in human diabetes and as such no health recommendation can be made.

Short-term effects of whole-grain wheat on appetite and food intake in healthy adults: a pilot study.

While it has been proposed, based on epidemiological studies, that whole grains may be beneficial in weight regulation, possibly due to effects on satiety, there is limited direct interventional evidence confirming this. The present cross-over study aimed to investigate the short-term effects on appetite and food intake of 48 g of whole-grain wheat (daily for 3 weeks) compared with refined grain (control). A total of fourteen healthy normal-weight adults consumed, within their habitual diets, either two whole-grain bread rolls (providing 48 g of whole grains over two rolls) or two control rolls daily for 3 weeks. Changes in food intake were assessed using 7 d diet diaries. Changes in subjective appetite ratings and food intake were also assessed at postprandial study visits. There were no significant differences between interventions in energy intake (assessed by the 7 d diet diaries and at the ad libitum test meal), subjective appetite ratings or anthropometric measurements. However, there was a significant difference between interventions for systolic blood pressure, which decreased during the whole-grain intervention and increased during the control intervention (-2 v. 4 mmHg; P = 0·015). The present study found no effect of whole grains on appetite or food intake in healthy individuals; however, 48 g of whole grain consumed daily for 3 weeks did have a beneficial effect on systolic blood pressure. The findings from the present study therefore do not support epidemiological evidence that whole grains are beneficial in weight regulation, although further investigation in other population groups (such as overweight and obese) would be required.