Are there interindividual differences in the reactive hypoglycaemia response to breakfast? A replicate crossover trial.

BACKGROUND: Following consumption of a meal, circulating glucose concentrations can rise and then fall briefly below the basal/fasting concentrations. This phenomenon is known as reactive hypoglycaemia but to date no researcher has explored potential inter-individual differences in response to meal consumption. OBJECTIVE: We conducted a secondary analysis of existing data to examine inter-individual variability of reactive hypoglycaemia in response to breakfast consumption. METHODS: Using a replicate crossover design, 12 healthy, physically active men (age: 18-30 y, body mass index: 22.1 to 28.0 kg⋅m- 2) completed two identical control (continued overnight fasting) and two breakfast (444 kcal; 60% carbohydrate, 17% protein, 23% fat) conditions in randomised sequences. Blood glucose and lactate concentrations, serum insulin and non-esterified fatty acid concentrations, whole-body energy expenditure, carbohydrate and fat oxidation rates, and appetite ratings were determined before and 2 h after the interventions. Inter-individual differences were explored using Pearson's product-moment correlations between the first and second replicates of the fasting-adjusted breakfast response. Within-participant covariate-adjusted linear mixed models and a random-effects meta-analytical approach were used to quantify participant-by-condition interactions. RESULTS: Breakfast consumption lowered 2-h blood glucose by 0.44 mmol/L (95%CI: 0.76 to 0.12 mmol/L) and serum NEFA concentrations, whilst increasing blood lactate and serum insulin concentrations (all p < 0.01). Large, positive correlations were observed between the first and second replicates of the fasting-adjusted insulin, lactate, hunger, and satisfaction responses to breakfast consumption (all r > 0.5, 90%CI ranged from 0.03 to 0.91). The participant-by-condition interaction response variability (SD) for serum insulin concentration was 11 pmol/L (95%CI: 5 to 16 pmol/L), which was consistent with the τ-statistic from the random-effects meta-analysis (11.7 pmol/L, 95%CI 7.0 to 22.2 pmol/L) whereas effects were unclear for other outcome variables (e.g., τ-statistic value for glucose: 0 mmol/L, 95%CI 0.0 to 0.5 mmol/L). CONCLUSIONS: Despite observing reactive hypoglycaemia at the group level, we were unable to detect any meaningful inter-individual variability of the reactive hypoglycaemia response to breakfast. There was, however, evidence that 2-h insulin responses to breakfast display meaningful inter-individual variability, which may be explained by relative carbohydrate dose ingested and variation in insulin sensitivity of participants.

The association between selenium status and global and attention specific cognition in very old adults in The Newcastle 85+ Study: cross-sectional and longitudinal analyses.

BACKGROUND: Selenium has potential safeguarding properties against cognitive decline, due to its role in protecting DNA, proteins, and lipids in the brain from oxidative damage. However, acute and chronic overexposure to selenium can be neurotoxic. OBJECTIVE: The aim of this analysis was to explore the association between selenium status (serum selenium and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity) and cognitive function in 85-year-olds living in Northeast England at baseline and up to 5 years of follow-up. METHODS: Global cognitive performance was assessed in 755 participants from the Newcastle 85+ study using the Standardized Mini-Mental State Examination (SMMSE) and attention-specific cognition was assessed using composite scores derived from the Cognitive Drug Research (CDR) System. Serum selenium, SELENOP and GPx3 activity were measured at baseline by total reflection X-ray fluorescence (TXRF), ELISA and coupled-enzyme reaction, respectively. Regression analyses explored linear and non-linear associations between continuous values and tertiles of selenium status biomarkers, respectively, and cognitive function at baseline. Generalized linear mixed models explored associations between continuous values and tertiles of selenium status biomarkers, and global cognitive decline over 5 years, and attention-specific cognitive decline over 3 years. RESULTS: Over 3 and 5 years, none of the selenium biomarkers were associated with the rate of cognitive decline. At baseline, in fully adjusted models, higher serum selenium was non-linearly associated with global cognition (ß 0.05±0.01, P=0.387 linear, ß 0.04±0.01, P=0.002 non-linear). SELENOP and GPx3 activity were not associated with any cognitive outcomes. CONCLUSIONS: There were no associations between selenium status and cognitive decline. However, serum selenium, but not SELENOP or GPx3 activity, was positively associated non-linearly with global cognition at baseline. Furthermore, these associations were not evident during follow-up, potentially due to residual confounding and reverse causation.

Elevations in plasma glucagon are associated with reduced insulin clearance after ingestion of a mixed-macronutrient meal in people with and without type 2 diabetes.

AIMS/HYPOTHESIS: The temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear. METHODS: In a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19). Pre-hepatic insulin secretion rates were determined by the deconvolution of C-peptide, and insulin clearance was calculated using a single-pool model. Insulin sensitivity was measured by an oral minimal model. RESULTS: There were divergent time course changes in insulin clearance between groups. In the Lean-NGT group, there was an immediate post-meal increase in insulin clearance compared with pre-meal values (p<0.05), whereas insulin clearance remained stable at baseline values in Obese-NGT or declined slightly in the type 2 diabetes group (p<0.05). The mean AUC for insulin clearance during the test was ~40% lower in the Obese-NGT (1.3 ± 0.4 l min-1 m-2) and type 2 diabetes (1.4 ± 0.7 l min-1 m-2) groups compared with Lean-NGT (1.9 ± 0.5 l min-1 m-2; p<0.01), with no difference between the Obese-NGT and type 2 diabetes groups. HOMA-IR and glucagon AUC emerged as predictors of insulin clearance AUC, independent of BMI, age or insulin sensitivity (adjusted R2=0.670). Individuals with increased glucagon AUC had a 40% reduction in insulin clearance AUC (~ -0.75 l min-1 m-2; p<0.001). CONCLUSIONS/INTERPRETATION: The ingestion of a mixed-macronutrient meal augments differing temporal profiles in insulin clearance among individuals without type 2 diabetes, which is associated with HOMA-IR and the secretion of glucagon. Further research investigating the role of hepatic glucagon signalling in postprandial insulin kinetics is warranted. TRIAL REGISTRATION: ISRCTN17563146 and ISRCTN95281775.

Appetite, food intake, and gut hormone responses to glycomacropeptide protein ingestion in older adults: A feasibility, acceptability, and pilot study.

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.

The Mediterranean diet is not associated with neuroimaging or cognition in middle-aged adults: a cross-sectional analysis of the PREVENT dementia programme.

BACKGROUND AND PURPOSE: The Mediterranean diet (MedDiet) has been associated with reduced dementia incidence in several studies. It is important to understand if diet is associated with brain health in midlife, when Alzheimer's disease and related dementias are known to begin. METHODS: This study used data from the PREVENT dementia programme. Three MedDiet scores were created (the Pyramid, Mediterranean Diet Adherence Screener [MEDAS] and MEDAS continuous) from a self-reported food frequency questionnaire. Primary outcomes were hippocampal volume and cube-transformed white matter hyperintensity volume. Secondary outcomes included cornu ammonis 1 and subiculum hippocampal subfield volumes, cortical thickness and measures of cognition. Sex-stratified analyses were run to explore differential associations between diet and brain health by sex. An exploratory path analysis was conducted to study if any associations between diet and brain health were mediated by cardiovascular risk factors for dementia. RESULTS: In all, 504 participants were included in this analysis, with a mean Pyramid score of 8.10 (SD 1.56). There were no significant associations between any MedDiet scoring method and any of the primary or secondary outcomes. There were no differences by sex in any analyses and no significant mediation between the Pyramid score and global cognition by cardiovascular risk factors. CONCLUSIONS: Overall, this study did not find evidence for an association between the MedDiet and either neuroimaging or cognition in a midlife population study. Future work should investigate associations between the MedDiet and Alzheimer's disease and related dementias biomarkers as well as functional neuroimaging in a midlife population.

Understanding engagement in diet and dementia prevention research among British South Asians: a short report of findings from a patient and public involvement group.

BACKGROUND: Dementia is a global public health challenge. Evidence suggests that individuals from South Asian communities are an at-risk group for dementia, partly as a result of early and cumulative exposure to known dementia risk factors, such as obesity and type 2 diabetes. There needs to be more culturally appropriate community engagement to increase awareness of dementia and identify better strategies to encourage participation in dementia-related research. METHODS: We aimed to better understand the barriers and facilitators towards engaging with, and participating in, diet and dementia related research among British South Asians. This was achieved using a public and patient involvement (PPI) approach. A community-based, engagement event involving information sharing from experts and roundtable discussions with South Asian communities (n = 26 contributors) was held in June 2023 in Newcastle-upon-Tyne, UK. Collaboration from preidentified PPI representatives (n = 3) informed the content and structure of PPI activities, as well as recruitment. Data were synthesised using template analysis, a form of codebook thematic analysis. This involved deductively analysing data using relevant a priori themes, which were expanded upon, or modified, via inductive analysis. RESULTS: The findings highlighted the importance of trust, representation and appreciation of cultural barriers as facilitators to engagement in diet and dementia risk reduction research. Consideration of language barriers, time constraints, social influences and how to embed community outreach activities were reported as driving factors to maximise participation. CONCLUSIONS: This PPI work will inform the design and co-creation of a culturally adapted dietary intervention for brain health in accordance with the Medical Research Council and National Institute for Health and Care Research guidance for developing complex interventions.

Nutrition for dementia prevention: a state of the art update for clinicians.

BACKGROUND AND OBJECTIVES: Dementia prevalence continues to rise. It is therefore essential to provide feasible and effective recommendations to encourage healthy brain ageing and reduce dementia risk across the population. Appropriate nutrition represents a potential strategy to mitigate dementia risk and could be recommended by clinicians as part of mid-life health checks and other health initiatives to reduce dementia prevalence. The purpose of this review is to provide a clinician-focused update on the current state of the knowledge on nutrition and dementia prevention. METHODS: Narrative review. RESULTS: Strong evidence exists to support the consumption of healthy, plant-based dietary patterns (e.g. Mediterranean, MIND or Nordic diet) for maintaining cognitive function and reducing dementia risk in later life and is supported by dementia prevention guideline from leading public health bodies (e.g. World Health Organization). Emerging evidence suggests potential cognitive benefits of consuming specific nutrients/foods (e.g. n-3 fatty acids or fish, flavonols and B-vitamins) and multi-nutrient compounds (e.g. Fortasyn Connect). Challenges and opportunities for integrating nutritional/dietary interventions for dementia prevention into clinical practice are explored in this review. CONCLUSIONS: Appropriate nutrition represents an important factor to help facilitate healthy cognitive ageing and allay dementia risk. The information provided in this article can help clinicians provide informed opinions on appropriate nutritional strategies as part of mid-life Health Checks and other risk reduction initiatives.

Adherence to the Eatwell Guide and cardiometabolic, cognitive and neuroimaging parameters: an analysis from the PREVENT dementia study.

BACKGROUND: The Eatwell guide reflects the UK government's recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. METHODS: Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimer's disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. RESULTS: A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (± 1.66) (out of a possible 12 points) and GEWG score of 39.88 (± 6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG ß: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG ß: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic ß: -0.24, 95% CI: -0.45, -0.03; diastolic ß: -0.16, 95% CI: -0.29, -0.03; BMI ß: -0.09, 95% CI: -0.16, -0.01). CONCLUSIONS: Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies.

Adherence to the Eatwell Guide and population and planetary health: A Rank Prize Forum report.

This report summarises a Forum conducted in June 2023 to explore the current state of the knowledge around the Eatwell Guide, which is the UK government's healthy eating tool, in relation to population and planetary health. The 1.5-day Forum highlighted the limited, albeit promising evidence linking higher adherence to the Eatwell Guide with favourable health outcomes, including reduced overall mortality risk, lower abdominal obesity in post-menopausal women and improved cardiometabolic health markers. Similarly, evidence was presented to suggest that higher adherence to the Eatwell Guide is associated with reduced greenhouse gas emissions. Presentations were given around cultural adaptations of the Eatwell Guide, including African Heritage and South Asian versions, which are designed to increase the acceptability and uptake of the Eatwell Guide in these communities in the United Kingdom. Presentations highlighted ongoing work relevant to the applications of the Eatwell Guide in randomised controlled trials and public health settings, including the development of a screening tool to quantify Eatwell Guide adherence. The Forum ended with a World Café-style event, in which the strengths and limitations of the Eatwell Guide were discussed, and directions for future research were identified. This Forum report serves as a primer on the current state of the knowledge on the Eatwell Guide and population and planetary health and will be of interest to researchers, healthcare professionals and public health officials.

Can artificial intelligence replace biochemists? A study comparing interpretation of thyroid function test results by ChatGPT and Google Bard to practising biochemists.

BACKGROUND: Public awareness of artificial intelligence (AI) is increasing and this novel technology is being used for a range of everyday tasks and more specialist clinical applications. On a background of increasing waits for GP appointments alongside patient access to laboratory test results through the NHS app, this study aimed to assess the accuracy and safety of two AI tools, ChatGPT and Google Bard, in providing interpretation of thyroid function test results as if posed by laboratory scientists or patients. METHODS: Fifteen fictional cases were presented to a team of clinicians and clinical scientists to produce a consensus opinion. The cases were then presented to ChatGPT and Google Bard as though from healthcare providers and from patients. The responses were categorized as correct, partially correct or incorrect compared to consensus opinion and the advice assessed for safety to patients. RESULTS: Of the 15 cases presented, ChatGPT and Google Bard correctly interpreted only 33.3% and 20.0% of cases, respectively. When queries were posed as a patient, 66.7% of ChatGPT responses were safe compared to 60.0% of Google Bard responses. Both AI tools were able to identify primary hypothyroidism and hyperthyroidism but failed to identify subclinical presentations, non-thyroidal illness or secondary hypothyroidism. CONCLUSIONS: This study has demonstrated that AI tools do not currently have the capacity to generate consistently correct interpretation and safe advice to patients and should not be used as an alternative to a consultation with a qualified medical professional. Available AI in its current form cannot replace human clinical knowledge in this scenario.

The Mediterranean diet is associated with better cardiometabolic health for women in mid-life but not men: A PREVENT dementia cohort cross-sectional analysis.

BACKGROUND AND AIMS: The Mediterranean diet (MedDiet) has been associated with better cardiovascular health in a number of studies. This study aimed to explore cross-sectional associations between MedDiet adherence in the PREVENT Dementia (PREVENT) programme, stratified by sex. METHODS AND RESULTS: Three MedDiet scores were calculated (MEDAS, MEDAS continuous and Pyramid) alongside a Western diet score. We used linear regression and linear mixed effects models to test for associations between the MEDAS score and cardiovascular health. Propensity scores were calculated to strengthen causality inferences from the data, and used as covariates along with total energy intake and Western diet scores. Exploratory analysis repeated the linear regression models for each individual food component. This study included 533 participants, with a mean age 51.25 (±5.40) years, and a majority of women (60.0%). Women had higher MedDiet scores across all three scoring methods, had a lower Western diet score and consumed fewer total calories. Higher MedDiet scores were associated with lower blood pressure, body mass index (BMI) and lower cardiovascular risk scores. When stratified by sex, women had significant positive associations between MedDiet scores and lower blood pressure, BMI and glycemia, whereas men only had a significant association with lower BMI. CONCLUSION: There were significant associations between higher MedDiet scores and a number of cardiovascular health outcome measures. These associations were seen more consistently for women compared to men, which may have implications for the development of personalised nutritional recommendations to improve cardiovascular health.

Mediterranean diet is associated with lower white matter lesion volume in Mediterranean cities and lower cerebrospinal fluid Aß42 in non-Mediterranean cities in the EPAD LCS cohort.

The Mediterranean diet (MedDiet) has been associated with better brain health and reduced incidence of dementia. Few studies have compared the effects of the MedDiet in early Alzheimer's disease or compared the effects of the diet within and outside of the Mediterranean region. The Mediterranean diet adherence screener (MEDAS) and MEDAS continuous scores were calculated at the baseline visit of the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (n = 1625). The scores were included in linear regression models to test for associations with hippocampal volume, log-transformed white matter lesion volume, cerebrospinal fluid pTau18, and Aß42. Higher MEDAS scores were associated with lower log-transformed white matter lesion volume (ß: -0.07, standard error [SE]: 0.02, p < 0.001). This association was only seen in the Mediterranean region (ß: -0.12, SE: 0.03, p < 0.001). In the non-Mediterranean region, higher MEDAS continuous scores were associated with lower cerebrospinal fluid Aß42 (ß: -68.30, SE: 14.32, p < 0.001). More research is needed to understand the differences in the associations seen with the MedDiet and Alzheimer's disease biomarkers in different European regions.

Recovery from Resistance Exercise in Older Adults: A Systematic Scoping Review.

BACKGROUND: Resistance exercise is recommended for maintaining muscle mass and strength in older adults. However, little is known about exercise-induced muscle damage and recovery from resistance exercise in older adults. This may have implications for exercise prescription. This scoping review aimed to identify and provide a broad overview of the available literature, examine how this research has been conducted, and identify current knowledge gaps relating to exercise-induced muscle damage and recovery from resistance exercise in older adults. METHODS: Studies were included if they included older adults aged 65 years and over, and reported any markers of exercise-induced muscle damage after performing a bout of resistance exercise. The following electronic databases were searched using a combination of MeSH terms and free text: MEDLINE, Scopus, Embase, SPORTDiscus and Web of Science. Additionally, reference lists of identified articles were screened for eligible studies. Data were extracted from eligible studies using a standardised form. Studies were collated and are reported by emergent theme or outcomes. RESULTS: A total of 10,976 possible articles were identified and 27 original research articles were included. Findings are reported by theme; sex differences in recovery from resistance exercise, symptoms of exercise-induced muscle damage, and biological markers of muscle damage. CONCLUSIONS: Despite the volume of available data, there is considerable variability in study protocols and inconsistency in findings reported. Across all measures of exercise-induced muscle damage, data in women are lacking when compared to males, and rectifying this discrepancy should be a focus of future studies. Current available data make it challenging to provide clear recommendations to those prescribing resistance exercise for older people.

The metabolic recovery of marathon runners: an untargeted 1H-NMR metabolomics perspective.

Introduction: Extreme endurance events may result in numerous adverse metabolic, immunologic, and physiological perturbations that may diminish athletic performance and adversely affect the overall health status of an athlete, especially in the absence of sufficient recovery. A comprehensive understanding of the post-marathon recovering metabolome, may aid in the identification of new biomarkers associated with marathon-induced stress, recovery, and adaptation, which can facilitate the development of improved training and recovery programs and personalized monitoring of athletic health/recovery/performance. Nevertheless, an untargeted, multi-disciplinary elucidation of the complex underlying biochemical mechanisms involved in recovery after such an endurance event is yet to be demonstrated. Methods: This investigation employed an untargeted proton nuclear magnetic resonance metabolomics approach to characterize the post-marathon recovering metabolome by systematically comparing the pre-, immediately post, 24, and 48 h post-marathon serum metabolite profiles of 15 athletes. Results and Discussion: A total of 26 metabolites were identified to fluctuate significantly among post-marathon and recovery time points and were mainly attributed to the recovery of adenosine triphosphate, redox balance and glycogen stores, amino acid oxidation, changes to gut microbiota, and energy drink consumption during the post-marathon recovery phase. Additionally, metabolites associated with delayed-onset muscle soreness were observed; however, the mechanisms underlying this commonly reported phenomenon remain to be elucidated. Although complete metabolic recovery of the energy-producing pathways and fuel substrate stores was attained within the 48 h recovery period, several metabolites remained perturbed throughout the 48 h recovery period and/or fluctuated again following their initial recovery to pre-marathon-related levels.

EQA: There's not a glitch in the matrix. Investigation of CRP bias on the Roche Cobas c701.

BACKGROUND: The Roche Cobas c Tina-quant C-Reactive Protein (CRP) IV method has shown persistent, significant negative bias compared to other methodologies in the UK NEQAS external quality assurance (EQA) scheme. The aim of this study was to compare CRP concentrations determined by this restandardized 4th generation assay with another commercially available method to assess the extent of any bias and impact on clinical cut-offs. METHODS: CRP concentrations in 38 anonymized patient serum samples were determined by a particle-enhanced immunoturbidimetric assay on the Roche Cobas c701 module and a latex assay on the Beckman Coulter AU5800 analyser over a concentration range of 1-308 mg/L. RESULTS: 97.4% samples analysed by the Roche Tina-quant CRP IV method demonstrated a negative bias compared to the Beckman AU latex method. The mean absolute bias was -4.12 mg/L (range: -19.13-10.93 mg/L; 95% CI: -17.25-9.01 mg/L). The mean relative difference was -15.5% (range: -40-4%; 95% CI: -33.03-1.94%). This bias was seen across the range of samples assayed, including at clinically significant cut-offs of 5 mg/L (-24% bias), 20 mg/L (-5%) and 100 mg/L (-13%). CONCLUSION: The negative bias of the Roche method demonstrated in the EQA scheme appears to reflect genuine differences in patient results, rather than an EQA matrix effect, despite re-standardization of the CRP assay. This report indicates that clinical cut-offs and reference ranges may be method-dependent, which should be reflected in published guidance and interpretation provided by laboratories.

Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: findings from the UK Biobank prospective cohort study.

BACKGROUND: The identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia. METHODS: We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested. RESULTS: Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65-0.91; PYRAMID: HR = 0.86, 95% CI = 0.73-1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia. CONCLUSIONS: Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.

Identifying behavioural barriers and facilitators to engaging men in a community-based lifestyle intervention to improve physical and mental health and well-being.

BACKGROUND: There are few community-based lifestyle interventions designed to target physical and mental health of men. We conducted a qualitative focus group study with men to explore their perceived barriers and facilitators to uptake and engagement with interventions designed to improve their physical and mental health and wellbeing. METHODS: A volunteer sampling approach (advertisements posted on a premier league football club's social media) was used to recruit men aged 28 to 65 years who were interested in improving their physical and/or mental health and wellbeing. Focus group discussions were conducted at a local premier league football club to 1) explore men's perceived barriers and facilitators to uptake of community-based interventions; 2) identify health issues considered important to address; 3) obtain participant views on how to best engage men in community-based interventions; and 4) use the findings to inform the development of a multibehavioural complex community-based intervention (called 'The 12th Man'). RESULTS: Six focus group discussions were conducted (duration 27 to 57 min) involving 25 participants (median age 41 years, IQR = 21 years). Thematic analyses generated seven themes: 'Lifestyle behaviours for both mental health and physical health'; 'work pressures are barriers to engaging with lifestyle behaviour change'; previous injuries are barriers to engagement in physical activity and exercise'; personal and peer group relationships impact on lifestyle behaviour change'; relationships between body image and self-confidence on mastery of skills for physical activity and exercise'; building motivation and personalised goal setting'; and 'credible individuals increase uptake and continued engagement with lifestyle behaviour change'. CONCLUSIONS: Findings suggest that a multibehavioural community-based lifestyle intervention designed for men should promote parity of esteem between physical and mental health. It should also acknowledge individual needs and preferences, emotions in the context of goal setting and planning, and be delivered by a knowledgeable and credible professional. The findings will inform the development of a multibehavioural complex community-based intervention ('The 12th Man').

Pre-Meal Whey Protein Alters Postprandial Insulinemia by Enhancing ß-Cell Function and Reducing Insulin Clearance in T2D.

CONTEXT: Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on ß-cell function and insulin kinetics remains unclear. OBJECTIVE: To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and ß-cell function. METHODS: This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and ß-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured. RESULTS: ß-cell function was 40% greater after WP (P = .001) and was accompanied with a -22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (-1.5 mmol/L and -16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133). CONCLUSION: In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in ß-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further ß-cell stimulation.Trial registry ISRCTN ID: ISRCTN17563146 Website link: www.isrctn.com/ISRCTN17563146.

Ageing modifies acute resting blood pressure responses to incremental consumption of dietary nitrate: a randomised, cross-over clinical trial.

Beetroot (BR) is a rich source of nitrate (NO3-) that has been shown to reduce blood pressure (BP). Yet, no studies have examined the vascular benefits of BR in whole-food form and whether the effects are modified by age. This study was a four-arm, randomised, open-label, cross-over design in twenty-four healthy adults (young n 12, age 27 ± 4 years, old n 12, age 64 ± 5 years). Participants consumed whole-cooked BR at portions of (NO3- content in brackets) 100 g (272 mg), 200 g (544 mg) and 300 g (816 mg) and a 200-ml solution containing 1000 mg of potassium nitrate (KNO3) on four separate occasions over a 4-week period (≥7-d washout period). BP, plasma NO3- and nitrite (NO2-) concentrations, and post-occlusion reactive hyperaemia via laser Doppler, were measured pre- and up to 5-h post-intervention. Data were analysed by repeated-measures ANOVA. Plasma NO2- concentrations were higher in the young v. old at baseline and post-intervention (P < 0·05). All NO3- interventions decreased systolic and diastolic BP in young participants (P < 0·05), whereas only KNO3 (at 240-300 min post-intake) significantly decreased systolic (-4·8 mmHg, -3·5 %, P = 0·024) and diastolic (-5·4 mmHg, -6·5 %, P = 0·007) BP in older participants. In conclusion, incremental doses of dietary NO3- reduced systolic and diastolic BP in healthy young adults whereas in the older group a significant decrease was only observed with the highest dose. The lower plasma NO2- concentrations in older participants suggest that there may be mechanistic differences in the production of NO from dietary NO3- in young and older populations.