Professor Denise Robertson

Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (-1.5 mmol/l mean PPG [95% CI -1.9, -1.1] by acarbose, and -1.6 [-1.9, -1.4] by miglitol) as compared to individuals without diabetes (-0.4 [95% CI -0.5, -0.3] by acarbose, and -0.6 [-0.8, -0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43-54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.

Background Patients with chronic pancreatitis experience malnutrition, osteoporosis, pancreatic exocrine insufficiency and have a 80% lifetime risk of diabetes (1). These are progressive consequences and require proactive surveillance for detection and optimisation of treatment. The NICE pancreatitis guidelines recommend long-term follow up for patients with chronic pancreatitis (1). European guidelines recommend regular assessment of bone density, biochemical assessment of micronutrient status and a comprehensive nutritional assessment (2). The aim of this survey was to assess compliance with the NICE guidelines by analysing current practice in patients with chronic pancreatitis after pancreaticoduodenectomy. Methods A UK wide electronic survey was developed using Qualtrics® software (SAP America Inc. USA) to capture all the nutritional aspects of follow-up thought to be relevant in the long term. Markers of endocrine failure and malnutrition (weight, nutritional assessment and biochemical, vitamin and mineral screens), smoking and alcohol cessation advice and the use of dual energy x-ray absorptiometry (DEXA) scans were included. The survey was piloted on 5 staff locally prior to being circulated through a professional network – the Pancreatic Society of Great Britain and Ireland (PSGBI). Data were analysed using Chi-Square tests in SPSS (Version 26). Results One hundred and one (23% response rate) clinicians completed the survey, with 83 useable data sets. Eighty eight percent worked in tertiary centres. Lifelong follow up was only offered in tertiary centres (n = 12) and was only provided by surgeons or dietitians (p = 0.03). The duration of follow up did not vary by region (p = 0.463). Patients in the South of England were more likely to undergo a micronutrient screen (p = 0.027). Only 26% of all patients were offered a DEXA scan. Clinicians with more than 10-years’ experience were more likely to assess weight (p = 0.039), glucose and HbA1c (p = 0.035) and assess symptoms (p = 0.031). Conclusions This survey demonstrated a need to improve the provision of long-term follow up for patients with chronic pancreatitis. Lack of clarity on the format and who within the clinical team should take responsibility may explain the lack of structured follow-up in this patient group. The importance of long-term assessment needs to be included in training programmes for junior clinicians, to standardise management, improve nutritional screening and improve access to bone mineral density scanning and diabetes screening. Responsibility for follow up should be agreed between primary, secondary and tertiary care.

Background Pancreatico-duodenectomy (PD) results in major anatomical changes that have an impact on nutritional status and quality of life. Issues such as pancreatic exocrine insufficiency (PEI), diabetes mellitus (DM), malnutrition, micronutrient deficiency, osteoporosis and other gastrointestinal diseases are common in the post-operative setting (1, 2). Appropriate treatment of these surgical consequences is associated with improved survival (3, 4), and should improve quality of life. The aim of this survey was to assess current practice and identify which disciplines were reviewing patients following PD, what format that review takes and the duration of follow up. Methods A UK wide electronic survey was developed using Qualtrics® software (SAP America Inc. USA) to capture all the nutritional aspects of follow up thought to be relevant in the long term. Markers of endocrine failure and malnutrition (weight, nutritional assessment and biochemical vitamin and mineral screens), smoking and alcohol cessation advice and the use of dual energy x-ray absorptiometry (DEXA) scans were included. The survey was piloted on 5 staff locally prior to being circulated through a professional network – the Pancreatic Society of Great Britain and Ireland (PSGBI). Data were analysed using Chi-Square tests in SPSS (Version 26). Results One hundred and one (23% response rate) clinicians completed the survey, with 83 useable data sets. Surgeons and dietitians were most likely to reply to the questionnaire, 88% of respondents worked in tertiary centres, half (55%) had more than 10 years’ experience. There were highly significant variations in practice according to clinician experience, underlying pathology, and institution (p 

Resistant starch (RS) is classed as a dietary fiber and does not contribute to the postprandial glucose excursion. Two types may be formed during food processing: RS3 when a starchy carbohydrate cools; RS5 when starch is heated in the presence of lipid. It is unknown whether RS5 can be produced under domestic cooking conditions or whether different fat types would affect the amount formed. Nor is it known whether sufficient RS3 remains after a chilled meal is reheated to have a significant impact on the postprandial glucose response. The aim of this study was to determine if different solid fat spreads (of varying fatty acid composition) incorporated into a mashed potato meal, served either freshly cooked or chilled and reheated, would produce different effects on the postprandial glucose and insulin responses. Ten healthy adults (age: 29 ± 5 y; BMI: 21.7 ± 2.6 kg/m2) attended six study days in a randomized crossover design. On each day, they consumed mashed potatoes (203 g) prepared with one of three solid fat spreads (butter, sunflower oil, olive oil, each providing 20 g fat). Each meal was consumed freshly cooked or microwave-reheated (after two days refrigeration at 4°C). Capillary blood samples were taken for 180 min postprandially. Plasma glucose and insulin were measured by glucose-oxidase method and ELISA respectively. Glucose incremental area under the curve (IAUC) was significantly lower for the reheated meal with butter, compared to the equivalent freshly cooked meal (P = 0.030). Insulinogenic Index (IGI), a surrogate measure of first phase insulin response, was significantly lower for the freshly cooked butter meal in comparison with the reheated equivalent (P = 0.031). There were no other differences between meals, either for fat type or preparation method. Differences in RS formation may explain these results; work is underway to measure both total RS and RS5. Other possible explanations are differences in effects on glucose absorption, such as via delayed gastric emptying. Whilst a beneficial effect on postprandial glucose and IGI was observed for the reheated butter meal, in comparison to the freshly cooked, it should be remembered that butter contains saturated fat, which has detrimental effects on blood lipids and should only be consumed in moderation. Biotechnology and Biological Sciences Research Council, UK.

Increased postprandial glycaemia and reduced insulin sensitivity are associated with development of Type 2 Diabetes (T2D). Maintaining a normal glucose response is important both for healthy individuals, for disease prevention, and for those with T2D, to prevent development of diabetes-related complications. Chilling previously-cooked starchy carbohydrate (CHO) results in retrogradation of some of the starch to form resistant starch (RS). RS is not absorbed in the small intestine and consequently does not contribute to the postprandial glucose excursion. Reheating the CHO, however, reverses this process, reducing some of the RS content. RS type 5 is formed in the laboratory by heating starch with free fatty acids; there is limited evidence for its formation using domestic cooking methods and real foods. Furthermore it is unclear whether this would translate into a noticeable effect on postprandial glucose metabolism. In this randomised crossover study, 8 participants attended two study days; at one they consumed a freshly cooked mashed potato meal (203 g boiled potato, 25 g butter) at the other they consumed an identical meal which had been chilled for 66 h then microwave reheated. The potatoes were intrinsically labelled with [U-13C]starch, and participants received a variable [6,6-2H2]glucose infusion, allowing detailed glucose flux modelling. Venous blood samples were taken for 6 h postprandially. There was no significant effect on postprandial glucose, however repeated measures ANOVA on postprandial insulin time-point data found a significant difference between meals (p = 0.026), with a 24% reduction in incremental area under the curve (0–120 min) and 21% reduction in insulin peak between freshly cooked and reheated meals. There were no significant effects on rate of appearance of glucose into the plasma from the gut (Ra) or on endogenous (hepatic) glucose production (EGP), however there was a strong trend for a reduced rate of glucose disposal (uptake into tissues, Rd) following the reheated meal (p = 0.054). It is hypothesised that RS was formed in the reheated meal by the chilling and reheating process; this will be verified by in vitro work later in the project. The attenuation of the postprandial insulin response with no significant effect on EGP suggests enhanced hepatic insulin sensitivity following the reheated meal as a possible mechanism for the effects of RS on postprandial glycaemia. This study demonstrates that making simple changes to the way a starchy carbohydrate meal is prepared can have significant beneficial effects on postprandial glucose metabolism.

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.

Malnutrition in chronic pancreatitis is complex and multifactorial, with malabsorption, pain, toxic dependencies and co-morbidities, such as diabetes, each playing a role. The aims of this systematic review were to assess the impact of nutritional intervention on markers of nutritional status in this complex patient group, A systematic review of EMBASE and PubMed was carried out in February 2020, identifying 2620 articles. After screening to exclude those reporting short term changes (less than 3 months), with only one data point, or in the wrong population, eight papers were selected for analysis. Seven studies documented the impact of a nutritional intervention, one was an observational study only. Overall, studies were limited by predominantly retrospective designs, heterogenous populations and poor control of potentially confounding variables. Data could not be combined due to variability in reporting methods. All studies exploring nutritional intervention, whether that consisted of advice by a specialist dietitian, dose escalation of pancreatic enzymes, oral nutritional supplements or enteral feeding, demonstrated improved body weight and pain control, whereas patients who did not receive an intervention deteriorated nutritionally. Patients with chronic pancreatitis benefit from nutritional intervention. Further work is required to explore the impact of nutritional intervention on body composition and functional outcomes.

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.

Background and aims Patients with pancreatic cancer often experience significant deterioration in nutritional status over time. Malnutrition is complex and multifactorial, with malabsorption, pain, toxic dependencies, co-morbidities and malignant processes all playing a role. The aims of this systematic review were to assess nutritional changes over time and identify tolerance of nutritional intervention, thus identifying potential areas for further research to improve patient outcomes. Materials and methods A systematic review of MEDLINE, EMBASE and PubMed was carried out in February 2020, identifying 2620 articles. After screening to exclude those reporting short-term measures, with only one data point, or in the wrong population, thirteen papers were selected for analysis (four trials in neo-adjuvant treatment, five in populations undergoing palliative treatment for pancreatic cancer, and four in mixed populations undergoing pancreatic resection). Results Overall, studies were limited by predominantly retrospective designs, and poor control of potentially confounding variables. Meta-analysis could not be performed due to heterogenicity in study design and reporting methods. Surgery in mixed cohorts did not appear to result in weight loss. Only one small intervention study was identified. Patients with pancreatic cancer experienced a decline in nutritional status, with 44-63% of patients undergoing neoadjuvant chemotherapy having low muscle mass prior to starting treatment. Conclusion There is a paucity of data regarding nutritional intervention in pancreatic cancer. Future work should include the use of validated functional and clinical assessment tools to further explore the impact of nutritional intervention, and the relationship between nutritional status and outcome.

Changes to the gut microbiota are reported in type 2 diabetes. The activity of the microbiota is integral in maintaining intestinal barrier function, disruption to which is proposed as a risk factor for the low-grade inflammation associated with insulin resistance. Can we target the microbiota through diet, and more specifically with prebiotics to improve barrier function and ultimately glycaemic control? This narrative review will discuss the evidence for barrier dysfunction in human type 2 diabetes and outline the recent evidence from clinical trials investigating the efficacy of prebiotics in glucose management. Copyright (c) 2020 John Wiley & Sons.

Purpose: Reducing postprandial hyperglycemia has beneficial effects on diabetesrelated risk factors, but the magnitude of the reduction needed to achieve such an effect is unknown. 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 glycaemia, 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 13004 screened papers, 14 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). 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: β = 0.085 (95% CI, 0.003, 0.167), k=14), but not with fasting insulin (β = 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: β = -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.

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 11y) 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.

Background: The relationship between Vitamin D (VitD) and insulin sensitivity and secretion in Type-2 diabetes (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-β). 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

Purpose Intermittent energy restriction (IER) is a popular weight loss (WL) strategy; however, its efficacy in clinical practice remains unknown. The present study compared the effects of IER compared to continuous energy restriction (CER) on WL and cardiometabolic risk factors in primary care. Methods A (self-selected) cohort study was conducted at the Rotherham Institute for Obesity (RIO), a primary care-based weight management service. 197(24% male) obese patients volunteered to participate and selected their diet group. IER participants (n = 99) consumed similar to 2600 kJ for two days/week. CER participants (n = 98) restricted their diet by similar to 2100 kJ/day below estimated requirements. Both interventions were delivered alongside RIO standard care. Changes in anthropometry and cardiometabolic disease risk markers (fasting biochemistry and blood pressure) were assessed after a 6-month intervention period and then participants were followed up again 6 months later (month 12). Results 27 IER patients (27%) and 39 CER patients (40%) completed the 6-month weight loss phase. Among completers, mean (SEM) WL was greater in the IER group at 6 months (5.4 +/- 1.1% versus 2.8 +/- 0.6%; p = 0.01), as were reductions in fat mass (p < 0.001) and improvements in systolic blood pressure (p < 0.001). Fasting insulin (p = 0.873) and diastolic blood pressure (p = 0.701) were reduced similarly in both groups. However, in the IER group, changes in anthropometry and blood pressure in the IER group had reverted to baseline by 12-month follow-up, whilst the CER group maintained weight loss but showed an increase in blood pressure. Conclusions Among completers, IER resulted in superior short-term changes in anthropometry and some cardiometabolic risk factors. However, rates of attrition and weight regain were higher compared with standard care, providing important insights in the implementations of IER within a "real-life" NHS setting.

A recent meta-analysis of prospective epidemiological studies found that increased nut consumption is associated with lower CVD risk(2) and another meta-analysis of randomised controlled trials reported that almonds reduced LDL-cholesterol whilst maintaining HDL-cholesterol(3). A 6-week randomised, controlled, parallel trial (ClinicalTrials.gov NCT02907684) in regular snack consumers at moderate risk of CVD (aged 30–70 y) was conducted aiming to investigate whether replacing habitual snacks (20% estimated daily energy requirements) with whole roasted almonds had any impact on blood lipid levels and insulin sensitivity. Estimated marginal mean changes from baseline following 6-week snack replacement intervention Mean of change values (95% CI) Variable Control group, n = 49 Almond group, n = 53 P value Total cholesterol (mmol/L) −0.00 (−0.19, 0.19) −0.22 (−0.41, −0.04) 0.096 Triglycerides (mmol/L) −0.08 (−0.19, 0.03) −0.03 (−0.13, 0.07) 0.464 LDL-cholesterol (mmol/L) 0.12 (−0.04, 0.29) −0.13 (−0.28, 0.03) 0.030* HDL-cholesterol (mmol/L) 0.02 (−0.07, 0.10) −0.06 (−0.14, 0.01) 0.170 Insulin (mlU/L) 1.46 (−0.02, 2.93) 0.62 (−0.76, 2.01) 0.416 Glucose (mmol/L) 0.05 (−0.13, 0.22) 0.06 (−0.10, 0.22) 0.928 HOMA-IR 0.42 (0.01, 0.83) 0.21 (−0.18, 0.59) 0.450 Adiponectin (mg/L) −0.26 (−0.94, 0.41) −0.16 (−0.80, 0.48) 0.831 Leptin (μg/L) −0.85 (−2.87, 1.17) 0.25 (−1.60, 2.10) 0.426 Resistin (μg/L) 0.09 (−0.27, 0.45) −0.00 (−0.34, 0.34) 0.707 Fetuin-A (mg/L) 15.18 (−23.18, 53.54) 4.33 (−31.71,40.36) 0.684 ANCOVA was used, adjusted for age, sex, baseline BMI and baseline variable value. *p < 0.05 indicates statistical significance.

There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined. We aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes, had any impact on markers of cardiometabolic health in adults aged 30–70 y at above-average risk of cardiovascular disease (CVD). The study was a 6-wk randomized controlled, parallel-arm trial. Following a 2-wk run-in period consuming control snacks (mini-muffins), participants consumed either whole roasted almonds (n = 51) or control snacks (n = 56), providing 20% of daily estimated energy requirements. Endothelial function (flow-mediated dilation), liver fat (MRI/magnetic resonance spectroscopy), and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point. Almonds, compared with control, increased endothelium-dependent vasodilation (mean difference 4.1%-units of measurement; 95% CI: 2.2, 5.9), but there were no differences in liver fat between groups. Plasma LDL cholesterol concentrations decreased in the almond group relative to control (mean difference −0.25 mmol/L; 95% CI: −0.45, −0.04), but there were no group differences in triglycerides, HDL cholesterol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, fetuin-A, body composition, pancreatic fat, intramyocellular lipids, fecal SCFAs, blood pressure, or 24-h heart rate variability. However, the long-phase heart rate variability parameter, very-low-frequency power, was increased during nighttime following the almond treatment compared with control (mean difference 337 ms2; 95% CI: 12, 661), indicating greater parasympathetic regulation. Whole almonds consumed as snacks markedly improve endothelial function, in addition to lowering LDL cholesterol, in adults with above-average risk of CVD. This trial was registered at clinicaltrials.gov as NCT02907684.

This pilot study explored the feasibility of a moderate time-restricted feeding (TRF) intervention and its effects on adiposity and metabolism. For ten weeks, a free-living TRF group (n=9) delayed breakfast and advanced dinner by 1.5-hours each. Changes in dietary intake, adiposity and fasting biochemistry (glucose, insulin, lipids) were compared to controls (n=7) who maintained habitual feeding patterns. Thirteen participants (29±2kg/m2) completed. The average daily feeding interval was successfully reduced in the TRF group (743±32 to 517±22 mins/day (p

The aim of the study was to investigate the effects of 24 h supplementation with resistant starch (RS; type 2) on postprandial insulin responses and appetite compared with a placebo (rapidly-digestible starch).

The intermittent energy restriction (IER) approach to weight-loss involves short periods of substantial (>70%) energy restriction 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. 27 (13 male) overweight/obese participants (46±3y, 30.1±1.0kg/m2) were randomised to either an IER (2638 kJ for two days/week with an overall ER of 22±0.3%, n=15) or CER (2510kJ below requirements with overall ER of 23±0.8%) intervention. Six-hour postprandial responses to a test meal and changes in anthropometry (fat mass, fat-free mass, circumferences) were assessed at baseline and upon attainment of 5% weight-loss, following a 7 day period of weight stabilisation. The study found no significant difference in the time to attain a 5% weight loss between groups (median 59 [41-70] days and 73 [48-128] days respectively, p=0.246), or in body composition (p≥0.430). For postprandial measures, neither diet significantly altered glycaemia (p=0.226), whereas insulinaemia was reduced comparatively (p=0.903). The reduction in c-peptide tended (p=0.057) to be greater following IER (309128±23268 to 247781±20709 pmol.360min.L-1) versus CER (297204±25112 to 301655±32714 pmol.360min.L-1). The relative reduction in triacylglycerol responses was greater (p=0.045) following IER (106±30 to 68±15 mmol.360min.L-1) compared to CER (117±43 to 130±31 mmol.360min.L-1). 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.

Background: Vinegar is promoted as a natural appetite suppressant, based on previous reports that vinegar ingestion significantly increases subsequent satiety. However there are concerns about the appropriateness and safety of this advice, and it is unclear if poor product palatability may explain previously published effects on appetite.Objective: To investigate if vinegar palatability and tolerability have a role in suppressing appetite and food intake in two sequential and related acute human feeding studies.Subjects and Methods: Healthy, young, normal weight unrestrained eaters were recruited to Study 1 (n=16), an acute feeding study supplying vinegar within both palatable and unpalatable drinks alongside a mixed breakfast in comparison to a non-vinegar control; and to Study 2 (n=14), a modified sham feeding study (taste only without ingestion) comparing vinegar to a non-vinegar control following a milkshake preload. Both studies were a randomized crossover balanced design for the assessment of appetite, energy intake and glycaemic response. Results: In Study 1, ingestion of vinegar significantly reduced quantitative and subjective measures of appetite, which were accompanied by significantly higher nausea ratings, with unpalatable treatment having the greatest effect. Significant correlations between palatability ratings and appetite measures were found. In Study 2, orosensory stimulation with vinegar did not influence subsequent subjective or quantitative measures of appetite compared with control.Conclusions:These studies indicate that vinegar ingestion enhances satiety whereas orosensory stimulation alone does not, and that these effects are largely due to poor tolerability following ingestion invoking feelings of nausea. On this basis the promotion of vinegar as a natural appetite suppressant does not seem appropriate. © 2014 Macmillan Publishers Limited All rights reserved.

Background & Aims: Serum lipids and lipoproteins are established biomarkers of cardiovascular disease risk that could be influenced by impaired gut barrier function via effects on the absorption of dietary and biliary cholesterol. The aim of this study was to examine the potential relationship between gut barrier function (gut permeability) and concentration of serum lipids and lipoproteins, in an ancillary analysis of serum samples taken from a previous study. Methods and Results: Serum lipids, lipoproteins and functional gut permeability, as assessed by the percentage of the urinary recovery of 51-Cr-labelled EDTA absorbed within 24h, were measured in a group of 30 healthy men. Serum lipopolysaccharide, high sensitivity C-reactive protein and interleukin-6 were also measured as markers of low-grade inflammation. The group expressed a 5- fold variation in total gut permeability (1.11 - 5.03%). Gut permeability was unrelated to the concentration of both serum total and low density lipoprotein (LDL)-cholesterol, but was positively associated with serum high density lipoprotein (HDL)-cholesterol (r=0.434, P=0.015). Serum HDL cholesterol was also positively associated with serum endotoxaemia (r=0.415, p=0.023). Conclusion: The significant association between increased gut permeability and elevated serum HDL-cholesterol is consistent with the role of HDL as an acute phase reactant, and in this situation, potentially dysfunctional lipoprotein. This finding may have negative implications for the putative role of HDL as a cardio-protective lipoprotein.

Context:High plasma triglycerides (TG) have been shown to be independent and better predictors of cardiovascular disease than low-density lipoprotein (LDL) cholesterol in women. This may be due to gender differences in very-low-density lipoprotein 1 (VLDL(1))- and VLDL(2)-TG and fatty acid kinetics.Objective:Our objective was to investigate whether there are differences in VLDL(1)- and VLDL(2)-TG and fatty acid kinetics in obese men and postmenopausal women, a high risk group for cardiovascular disease.Research Design and Methods:Stable isotopes techniques were used to measure fasting palmitate rate of appearance, metabolic clearance rate, oxidation rate, and nonoxidative disposal rate, VLDL(1)-TG and VLDL(2)-TG fractional catabolic rate (FCR) and production rate (PR). Whole-body fat distribution was measured by magnetic resonance imaging.Participants:Participants included 10 postmenopausal obese women and eight obese men matched for age, body mass index, and fasting plasma TG.Results:The women had lower visceral fat and higher sc fat than the men (P < 0.001 and P < 0.002). Palmitate rate of appearance, metabolic clearance rate, nonoxidative disposal rate, and oxidation rate corrected for resting energy expenditure were greater in the women than the men (all P < 0.03). VLDL(2)-TG PR corrected for fat-free mass was higher in the women (P < 0.001). VLDL(2)-TG and VLDL(2)-cholesterol pools were higher in the women (P < 0.001 and P < 0.008). VLDL(1)-TG FCR and PR and VLDL(2)-TG FCR were not different between genders.Conclusion:Fatty acid and VLDL(2)-TG flux is higher in postmenopausal obese women than in obese men matched for fasting plasma TG levels.

The impact of eating behaviours on circulating levels of appetite-regulating hormones remains largely unknown. The aims of this study were to assess the role of restraint and disinhibition on fasting/postprandial peptide YY (PYY) plasma levels and subjective feelings of appetite in normal-weight individuals and to determine whether the effect was energy load dependent. 33 participants (12 men) were classified as restrained/unrestrained and low/high in disinhibition based on Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint/disinhibition on PYY plasma levels and feelings of appetite was measured, after a 500kcal and 1000kcal breakfast, using a randomised crossover design. Restraint did not impact on either fasting or postprandial PYY plasma levels, but participants with high disinhibition had a tendency towards a blunted postprandial PYY response. Moreover, restrained eaters reported lower ratings of prospective food consumption postprandially, and a tendency towards higher fullness/lower hunger. In conclusion, circulating PYY is unaffected by restrained eating behaviour, despite being associated with increased fullness and reduced hunger in the fed state. High levels of disinhibition tend to be associated with a blunted PYY response and this may contribute towards the susceptibility to overconsumption and increased risk of weight gain characteristic of this trait.

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 intestinal permeability, glucose tolerance, and intestinal bacteria in human type 2 diabetes. Twenty-nine males with well-controlled type 2 diabetes were randomised to a prebiotic (galactooligosaccharide mixture) or placebo (maltodextrin) supplement (5.5g/day 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 IVGTT. 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. It is also plausible that prebiotics may play a more important role in prevention rather than in the treatment of human type 2 diabetes.

Type 2 diabetes (T2D) has been linked with increased intestinal permeability, but the clinical significance of this phenomenon is unknown. The objective of this study was to investigate the potential link between glucose control, intestinal permeability, diet and intestinal microbiota in patients with T2D. Thirty-two males with well-controlled T2D and 30 age-matched male controls without diabetes were enrolled in a case-control study. Metabolic parameters, inflammatory markers, endotoxaemia and intestinal microbiota in individuals subdivided into high (HP) and normal (LP) colonic permeability groups, were the main outcomes. In T2D, the HP group had significantly higher fasting glucose (P = 40 0.034) and plasma non-esterified fatty acid levels (P = 0.05) compared with the LP group. Increased colonic permeability was also linked with altered abundances of selected microbial taxa. The microbiota of both T2D and control HP groups was enriched with Enterobacteriales. In conclusion, high intestinal permeability was associated with poorer fasting glucose control in T2D patients and changes in some microbial taxa in both T2D patients and non-diabetic controls. Therefore, enrichment in the gram- negative order Enterobacteriales may characterise impaired colonic permeability prior to/independently from a disruption in glucose tolerance.

Obesity is a global epidemic; increased consumption of energy-dense food and reduced physical activity levels are likely to be the main drivers. Previous cross-sectional research has shown that sedentary males, unlike their active counterparts, are unable to compensate for previous energy intake (EI). Using a longitudinal design a 6-week exercise intervention was found to improve short-term appetite control, leading to a more 'sensitive' eating behaviour in response to previous EI, both acutely at a test meal and for the next 24 h. Although the mechanisms whereby acute and chronic exercise improves short-term appetite remain unknown, post-ingestive satiety peptides are likely to be involved. Acute exercise was found to increase postprandial levels of polypeptide YY, glucagon-like peptide-1 and pancreatic polypeptide but to have no impact on ghrelin, suggesting that exercise can trigger physiological changes in satiety hormone secretion that could help in appetite control and weight maintenance. In the context of an increased availability of highly-palatable food, dietary restraint may be increasingly important. Although restraint has been associated with abnormal eating behaviour, in the laboratory no counter-regulation was found in restrained eaters when presented with a buffet meal 60 min after a high-energy preload or when a pasta-meal was presented 3 h after preloading. Although restraint was not found to impact on polypeptide YY or TAG, lower postprandial glucose and insulin plasma levels were observed in restrained eaters, together with increased feelings of fullness. In conclusion, short-term appetite control seems to be favourably modified by exercise, while the impact of restraint on appetite seems to be more complex.

Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM). We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45-65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO), nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p

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.

OBJECTIVE Previous animal studies suggest a functional relationship between metabolism, type 2 diabetes, and the amplitude of daily rhythms in white adipose tissue (WAT). However, data interpretation is confounded by differences in genetic background and diet or limited sampling points. We have taken the novel approach of analyzing serial human WAT biopsies across a 24-h cycle in controlled laboratory conditions.RESEARCH DESIGN AND METHODS Lean (n = 8), overweight/obese (n = 11), or overweight/obese type 2 diabetic (n = 8) volunteers followed a strict sleep-wake and dietary regimen for 1 week prior to the laboratory study. They were then maintained in controlled light-dark conditions in a semirecumbent posture and fed hourly during wake periods. Subcutaneous WAT biopsies were collected every 6 h over 24 h, and gene expression was measured by quantitative PCR.RESULTS Lean individuals exhibited significant (P < 0.05) temporal changes of core clock (PERI, PER2, PER3, CRY2, BMAL1, and DBP) and metabolic (REVERB alpha,RIP140, and PGC1 alpha) genes. The BMAL1 rhythm was in approximate antiphase with the other clock genes. It is noteworthy that there was no significant effect (P > 0.05) of increased body weight or type 2 diabetes on rhythmic gene expression.CONCLUSIONS The robust nature of these rhythms and their relative phasing indicate that WAT now can be considered as a peripheral tissue suitable for the study of in vivo human rhythms. Comparison of data between subject groups clearly indicates that obesity and type 2 diabetes are not related to the amplitude of rhythmic WAT gene expression in humans maintained under controlled conditions. Diabetes 60:1577-1581, 2011

Exercise is capable of influencing the regulation of energy balance by acutely modulating appetite and energy intake coupled to effects on substrate utilization. Yet, few studies have examined acute effects of exercise intensity on aspects of both energy intake and energy metabolism, independently of energy cost of exercise. Furthermore, little is known as to the gender differences of these effect. One hour after a standardised breakfast, 40 (19 female), healthy participants (BMI 23.6±3.6 kg.m-2, VO2peak 34.4±6.8 ml.min-1.min-1) undertook either High intensity intermittent cycling consisting of 8 repeated 60s bouts of cycling at 95% VO2peak (HIIC) or low intensity continuous cycling, equivalent to 50% VO2peak (LICC), matched for energy cost (~950kJ) followed by 90mins of rest, in a randomised crossover design. Throughout each study visit satiety was assessed subjectively using visual analogue scales alongside blood metabolites and GLP-1. Energy expenditure and substrate utilization were measured over 75 minutes post-exercise via indirect calorimetry. Energy intake was assessed for 48hours post-intervention. No differences in appetite, GLP-1 or energy intakes were observed between HIIC and LICC, with or without stratifying for gender. Significant differences in post exercise non-esterified fatty acid (NEFA) concentrations were observed between intensities in both genders, coupled to a significantly lower respiratory exchange ratio (RER) following HIIC (P=0.0028), with a trend towards greater reductions in RER in men(P=0.079). In conclusion, high intensity exercise, if energy matched, does not lead to greater appetite or energy intake but may exert additional beneficial metabolic effects that may be more pronounced in males.

This pilot study investigated the effects of chilling and reheating a pasta-based meal on the postprandial glycaemic response. In this single-blind crossover study, 10 healthy volunteers consumed identical pasta meals (pasta, olive oil and tomato sauce), served either freshly prepared, chilled or chilled/reheated, on three separate randomised occasions. Capillary blood samples were taken for two hours postprandially. A significant difference in glucose Incremental Area Under the Curve (IAUC) was observed (p = 0.006), with the greatest difference observed between the freshly cooked and chilled/reheated meals (p = 0.041). Significant differences in incremental peak glucose were also observed (p = 0.018). These results suggest that making simple changes to domestic food processing methods can reduce the glycaemic excursion following a pasta meal, with the potential for health benefit.

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.

In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes.

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.

Objectives: Evidence for a causal relationship between sleep-loss and metabolism is derived primarily from short-term sleep deprivation studies in the laboratory. The objective of this study was to investigate whether small changes in sleep duration over a three week period while participants are living in their normal environment lead to changes in insulin sensitivity and other metabolic parameters. Methods: Nineteen healthy, young, normal-weight men were randomised to either sleep restriction (habitual bedtime minus 1.5 h) or a control condition (habitual bedtime) for three weeks. Weekly assessments of insulin sensitivity by hyperinsulinaemic-euglycaemic clamp, anthropometry, vascular function, leptin and adiponectin were made. Sleep was assessed continuously using actigraphy and diaries. Results: Assessment of sleep by actigraphy confirmed that the intervention reduced daily sleep duration by 01:19 ± 00:15 (SE; p < 0.001). Sleep restriction led to changes in insulin sensitivity, body weight and plasma concentrations of leptin which varied during the three week period. There was no effect on plasma adiponectin or vascular function. Conclusions: Even minor reductions in sleep duration lead to changes in insulin sensitivity, body weight and other metabolic parameters which vary during the exposure period. Larger and longer longitudinal studies of sleep restriction and sleep extension are warranted. © 2013 Elsevier Inc.

Background:There is evidence linking oral propionate to a reduction in food intake, which could confer functional food properties in the fight against obesity. However, propionate is typically volatile with a pungent smell and taste and so incorporating into foods naturally, at levels acceptable to the consumer is a novel approach.Subjects/methods:Twenty healthy, young, normal weight unrestrained eaters underwent an acute feeding study using a palatable sourdough and an identical control bread of a similar palatability, in a randomized cross-over balanced design for the assessment of appetite and energy intake.Results:No difference in energy intake of an ad libitum test meal, 180 min after the bread-based breakfast or in energy and macronutrient intake over the entire 24 h period was found between breads. Visual analogue scale ratings for appetite were not influenced by bread type, except the desire to eat something sweet. Elevated plasma insulin concentrations were observed following the propionate-rich sourdough breakfast (P0.033 no effects of treatment on postprandial glycaemia were found.Conclusions:These findings suggest propionate-rich sourdough bread does not influence appetite and food intake unlike larger doses of the food preservative N-propionate. © 2012 Macmillan Publishers Limited.

Potatoes have been an affordable, staple part of the diet for many hundreds of years. Recently however, there has been a decline in consumption, perhaps influenced by erroneous reports of being an unhealthy food. This review provides an overview of the nutritional value of potatoes and examines the evidence for associations between potato consumption and non-communicable diseases. Potatoes are an important source of micronutrients, such as vitamin C, vitamin B6, potassium, folate, and iron and contribute a significant amount of fibre to the diet. However, nutrient content is affected by cooking method; boiling causes leaching of water-soluble nutrients, whereas frying can increase the resistant starch content of the cooked potato. Epidemiological studies have reported associations between potato intake and obesity, type 2 diabetes and cardiovascular disease. However, results are contradictory and confounded by lack of detail on cooking methods. Indeed, potatoes have been reported to be more satiating than other starchy carbohydrates, such as pasta and rice, which may aid weight maintenance. Future research should consider cooking methods in the study design in order to reduce confounding factors and further explore the health impact of this food.

Context: Dietary fibers have been associated with a reduced incidence of type 2 diabetes mellitus in epidemiological studies; however, the precise mechanisms are unknown. Objective: The objective of the study was to evaluate the efficacy and site of action of an insoluble dietary fiber derived from maize (HAM-RS2) in improving insulin resistance in subjects at increased risk of type 2 diabetes mellitus. Design: This study was a randomized, controlled crossover, dietary intervention study. Setting: The study was conducted at the Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Participants: Fifteen men and women with insulin resistance participated in the study. Intervention: The intervention included 40 g/d HAM-RS2 compared with a matched placebo for 8 wk. Main Outcome Measures: After each supplement, participants underwent a two-step hyperinsulinemic-euglycemic clamp study with the addition of glucose tracers; a meal tolerance test; arteriovenous sampling across forearm muscle tissue; and a sc adipose tissue biopsy for assessment of gene expression. Results: There was enhanced uptake of glucose into the forearm muscle measured by arteriovenous sampling (65 ± 15% increase after resistant starch; P < 0.001). Adipose tissue function was also affected, with enhanced fatty acid suppression after HAM-RS2 treatment and an increase in gene expression for hormone sensitive lipase (P = 0.005), perilipin (P = 0.011), lipoprotein lipase (P = 0.014), and adipose triglyceride lipase (P = 0.03) in biopsy samples. There was no effect on the insulin sensitivity of hepatic glucose production or plasma lipids after HAM-RS2. Conclusion: HAM-RS2 improved peripheral but not hepatic insulin resistance and requires further study as an intervention in patients with or at risk for type 2 diabetes.

The recently discovered SCFA-activated G-coupled protein receptors FFA receptor 2 and FFA receptor 3 are co-localised in l-cells with the anorexigenic 'ileal brake' gut hormone peptide YY, and also in adipocytes, with activation stimulating leptin release. Thus, SCFA such as acetate and propionate show promise as a candidate to increase satiety-enhancing properties of food. We therefore postulate SCFA may have a role in appetite regulation and energy homeostasis. SCFA can be delivered either directly within food, or indirectly via the colon by the provision of fermentable non-digestible carbohydrates. A review of studies investigating the effects of oral SCFA ingestion on appetite suggests that while oral SCFA ingestion is associated with enhanced satiety, this may be explained by product palatability rather than a physiological effect of SCFA. Colon-derived SCFA generated during microfloral fermentation have also been suggested to explain satiety-enhancing properties of non-digestible carbohydrates. However, findings are mixed from investigations into the effects of the prebiotic inulin-type fructans on appetite. Overall, data presented in this review do not support a role for SCFA in appetite regulation.

Aims Diets rich in non-viscous fibre are linked to a reduced risk of both diabetes and cardiovascular disease; however, the mechanism of action remains unclear. This study was undertaken to assess whether chronic consumption of this type of fibre in individuals with the metabolic syndrome would improve insulin sensitivity via changes in ectopic fat storage. Methods The study was a single-blind, randomized, parallel nutritional intervention where 20 insulin resistant subjects consumed either the fibre supplement (resistant starch) (40 g/day) or placebo supplement (0 g/day) for 12 weeks. Insulin sensitivity was measured by euglycaemic-hyperinsulinaemic clamp and ectopic fat storage measured by whole-body magnetic resonance spectroscopy. Results Resistant starch consumption did not significantly affect body weight, fat storage in muscle, liver or visceral depots. There was also no change with resistant starch feeding on vascular function or markers of inflammation. However, in subjects randomized to consume the resistant starch, insulin sensitivity improved compared with the placebo group (P = 0.023). Insulin sensitivity correlated significantly with changes in waist circumference and fat storage in tibialis muscle and to a lesser extent to visceral-to-subcutaneous abdominal adipose tissue ratio. Conclusion Consumption of resistant starch improves insulin sensitivity in subjects with the metabolic syndrome. Unlike in animal models, diabetes prevention does not appear to be directly related to changes in body adiposity, blood lipids or inflammatory markers. Further research to elucidate the mechanisms behind this change in insulin sensitivity in human subjects is required. © 2010 Diabetes UK.

Purpose of review: Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the enteroinsular axis, stimulating insulin secretion. In addition, it has extrapancreatic actions, which may have pathophysiological relevance. This review highlights recent findings with regard to GIP's actions both within the enteroinsular axis and beyond it, and discusses evidence for the therapeutic potential of GIP receptor agonists and antagonists for the treatment of type 2 diabetes mellitus and possibly obesity. Recent findings: GIP signalling pathways have been investigated using transgenic animal models, either lacking or overexpressing a defective GIP receptor. The dependence of early-phase insulin potentiation by GIP on KATP channel activity, and of late-phase insulin secretion on other signals, has been demonstrated. GIP receptor agonists and antagonists resistant to enzymatic degradation and with a greater potency than native GIP have recently been developed. Their activity in animal studies suggests a novel and effective treatment of type 2 diabetes. Extrapancreatic actions of GIP have received little recent attention, with notable exceptions being the investigation of aberrant GIP receptor expression in Cushing's disease, and a possible role for GIP in vascular endothelial function. Summary: The role of GIP in stimulating insulin secretion continues to be a primary focus for research, and the availability of various GIP-receptor knockout mice have helped to elucidate GIP's signalling pathways. A range of GIP receptor agonists and antagonists show promise in the treatment of type 2 diabetes, but as yet no clinical studies have been undertaken. Studies implicating GIP beyond the enteroinsular axis remain few and often negative, with the exception of effects on the vascular endothelium and the adrenal gland. © 2006 Lippincott Williams & Wilkins.

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 single nucleotide polymorphism (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 4 cups/day instant coffee for 12 weeks or a control group (n=8) who remained coffee/caffeine free. Venous blood samples were taken pre- and post13 intervention. Primary analysis revealed no significant differences between groups. Analysis of the coffee group by genotype revealed several differences. Prior to coffee intake, the AC genotype (“slow” caffeine metabolisers, n=9) displayed higher baseline glucose and non esterified fatty acids (NEFA) than the AA genotype (“fast” caffeine metabolisers, n=10, p

Background: Numerous research have found an association between vitamin D (vitD) status and single nucleotide polymorphisms (SNPs) in genes involved in vitD metabolism. It is notable that the influence of these SNPs on 25-hydroxyvitamin D (25(OH)D) levels might vary in different populations. We aimed in this study to explore for genetic variants in genes related to vitD metabolism in families with vitD deficiency in Saudi Arabia using whole exome sequencing (WES). Methods: This family-based WES study was conducted for 21 families with vitD deficiency (n=39) from Saudi Arabia. WES was performed for DNA samples, then obtained WES data was filtered and a number of variants were prioritized and validated by Sanger DNA sequencing. Results: Several missense variants in vitD related genes were detected in families. We determined two variants in Low-density lipoprotein 2 gene (LRP2) with one variant (rs2075252) observed in six individuals, while the other LRP2 variant (rs4667591) was detected in 13 subjects. Single variant in 7-dehydrocholesterol reductase (DHCR7) (rs143587828) and melanocortin 1 receptor (MC1R) (rs1805005) gene were observed in 2 subjects of 2 different families. Other variants in group-specific component (GC), cubilin (CUBN) and calcium-sensing receptor (CASR) gene were seen in index cases and controls. Polymorphisms in GC (rs9016) and CASR (rs1801726) were seen in majority of family cases (94% and 88%) respectively. Conclusion: In vitD deficient families in Saudi Arabia, we were able to detect a number of missense exonic variants including variants in GC (rs9016), CUBN (rs1801222), CASR (rs1801726) and LRP2 (rs4667591). However, the existence of these variants was not different between affected family members and non-affected controls. Additionally, we were able to find a mutation in DHCR7 (rs143587828) and a polymorphism in LRP2 (rs2075252) which may affect vitD levels and influence vitD status. However, further studies are required to confirm the association of these variants with vitD deficiency.

Background: Measurement of free 25-hydroyvitamin D [25(OH)D] status has been suggested as a more representative marker of vitamin D status than that of total 25(OH) D. Previously, free 25(OH)D could only be calculated indirectly; however, a newly developed direct assay for the measurement of free 25(OH)D is now available. The aim of this study therefore was to investigate directly measured total and free vitamin D levels association with metabolic health in postmenopausal healthy women living in Saudi Arabia. Methods: A sample of 302 postmenopausal women aged ≥ 50 years (n=302) living in Saudi Arabia were recruited in a cross-section study design. Blood samples were collected from subjects for measurement of serum levels of total 25(OH)D, directly measured free 25(OH)D, metabolic bone parameters, lipid profile, and other biochemical tests. Results: A positive correlation was found between directly measured free and total 25(OH)D (r=0.64, P

Background Group-specific component (GC) and cytochrome P450 Family 2 Subfamily R Member 1 (CYP2R1) genes are one of the vital genes involved in the vitamin D (vitD) metabolic pathway. Association of genetic polymorphisms in these two genes with 25-hyroxyvitamin D (25(OH)D) level has been reported in several studies. However, this association has been reported to be discrepant among populations from different ethnicities. Therefore, we aimed in this study to investigate association of the two major single nucleotide polymorphisms (SNP) in GC (rs4588 and rs7014) and a SNP (rs12794714) in CYP2R1 in postmenopausal women in Saudi Arabia. Methods This study randomly selected 459 postmenopausal women (aged ≥ 50 years) of multiple ethnicities in Jeddah, Saudi Arabia. Blood samples were collected from all participating women for DNA extraction and for assessment of serum levels of total 25(OH)D, directly measured free 25(OH)D and other biochemical parameters. SNPs in selected vitD related genes (rs4588 in GC, c.1364G>T with transcript ID: NM_001204307.1 and rs7041 in GC, c.1353A>C with transcript ID NM_001204307.1 and rs12794714 in CYP2R1, c.177G>A with transcript ID NM_024514.4) were determined in DNA samples using Sanger DNA sequencing. Results Minor allele frequency for rs4588, rs7041 and rs12794714 were 0.25, 0.44 and 0.42 respectively. Genotypes of rs7041 showed significant difference in total 25(OH)D level but not in free 25(O)D level (P=0.023). In comparison, genotypes of rs4588 and rs12794714 did not show any significant difference neither in total nor in free 25(OH)D level. Post hoc test revealed that total 25(OH)D was lower in the rs7041 TT allele compared to the GG allele (P=0.022). Chi-square test showed that vitD status was associated with rs7041 genotypes (P=0.035). In addition, rs7041 minor alleles were found to have an association with vitD deficiency with a statistical significant odds ratio (>1) of 2.24 and 3.51 with P=0.006 and P=0.007 for TG and GG genotypes respectively. Conclusion The rs7041 SNP in GC was associated with total 25(OH)D level in postmenopausal women in Saudi Arabia, while rs4588 in GC and rs12794714 in CYP2R1 did not show association with total 25(OH)D. Further studies exploring additional variants in vitD related genes are needed to understand genetic factors underlying vitD deficiency in Saudi population.

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.