Chrono-medicine considers circadian biology in disease management, including combined lifestyle and medicine interventions. Exercise and nutritional interventions are well-known for their efficacy in managing type 2 diabetes, and metformin remains a widely used pharmacological agent. However, metformin may reduce exercise capacity and interfere with skeletal muscle adaptations, creating barriers to exercise adherence. Research into optimising the timing of exercise has shown promise, particularly for glycaemic management in people with type 2 diabetes. Aligning exercise timing with circadian rhythms and nutritional intake may maximise benefits. Nutritional timing also plays a crucial role in glycaemic control. Recent research suggests that not only what we eat but when we eat significantly impacts glycaemic control, with strategies like time-restricted feeding (TRF) showing promise in reducing caloric intake, improving glycaemic regulation and enhancing overall metabolic health. These findings suggest that meal timing could be an important adjunct to traditional dietary and exercise approaches in managing diabetes and related metabolic disorders. When taking a holistic view of Diabetes management and the diurnal environment, one must also consider the circadian biology of medicines. Metformin has a circadian profile in plasma, and our recent study suggests that morning exercise combined with pre-breakfast metformin intake reduces glycaemia more effectively than post-breakfast intake. In this review, we aim to explore the integration of circadian biology into type 2 diabetes management by examining the timing of exercise, nutrition and medication. In conclusion, chrono-medicine offers a promising, cost-effective strategy for managing type 2 diabetes. Integrating precision timing of exercise, nutrition and medication into treatment plans requires considering the entire diurnal environment, including lifestyle and occupational factors, to develop comprehensive, evidence-based healthcare strategies.

By 2050 the number of adults living with obesity in the UK will rise with approximately one in four in the adult population. This rising trend is not equitable, with higher prevalence in socially disadvantaged groups. There is an apparent paradox of not being able to provide food for the family to eat, a feature of food insecurity and living with obesity. With the current cost-of-living crisis, there is a challenge to afford both food and fuel bills. Environmentally sustainable and healthy diets are proposed to improve public health and reduce the impact of the food system on the environment, while also improving diet quality. However, healthier foods tend to be nearly three times more expensive than unhealthy foods, and this provides a challenge for citizens on low incomes. In this review, we explore some of the evidence for solutions in the retail food environment to support the UK food system to be safe, nutritious, environmentally friendly and fair for all. We highlight the value of co-production in research, to give value and power to the lived experience to address these inequalities. Our multidisciplinary research approach within the FIO Food research grant will generate new insights into modifiable and potentially impactful changes to the UK food system, specifically for the retail food sector. We believe that the co-creation, design and delivery of research with those living with obesity and food insecurity will help to transform the UK food system for health and the environment in this vulnerable group.

Metabolites produced by microbial fermentation in the human intestine, especially short-chain fatty acids (SCFAs), are known to play important roles in colonic and systemic health. Our aim here was to advance our understanding of how and why their concentrations and proportions vary between individuals. We have analysed faecal concentrations of microbial fermentation acids from 10 human volunteer studies, involving 163 subjects, conducted at the Rowett Institute, Aberdeen, UK over a 7-year period. In baseline samples, the % butyrate was significantly higher, whilst % iso-butyrate and % iso-valerate were significantly lower, with increasing total SCFA concentration. The decreasing proportions of iso-butyrate and iso-valerate, derived from amino acid fermentation, suggest that fibre intake was mainly responsible for increased SCFA concentrations. We propose that the increase in % butyrate among faecal SCFA is largely driven by a decrease in colonic pH resulting from higher SCFA concentrations. Consistent with this, both total SCFA and % butyrate increased significantly with decreasing pH across five studies for which faecal pH measurements were available. Colonic pH influences butyrate production through altering the stoichiometry of butyrate formation by butyrate-producing species, resulting in increased acetate uptake and butyrate formation, and facilitating increased relative abundance of butyrate-producing species (notably Roseburia and Eubacterium rectale).

High-protein diets are an effective means for weight loss (WL), but the mechanisms are unclear. One hypothesis relates to the release of gut hormones by either protein or amino acids (AA). The present study involved overweight and obese male volunteers (n 18, mean BMI 36·8 kg/m2) who consumed a maintenance diet for 7 d followed by fully randomised 10 d treatments with three iso-energetic WL diets, i.e. with either normal protein (NP, 15 % of energy) or high protein (HP, 30 %) or with a combination of protein and free AA, each 15 % of energy (NPAA). Psychometric ratings of appetite were recorded hourly. On day 10, plasma samples were taken at 30 min intervals over two consecutive 5 h periods (covering post-breakfast and post-lunch) and analysed for AA, glucose and hormones (insulin, total glucose-dependent insulinotropic peptide, active ghrelin and total peptide YY (PYY)) plus leucine kinetics (first 5 h only). Composite hunger was 16 % lower for the HP diet than for the NP diet (P< 0·01) in the 5 h period after both meals. Plasma essential AA concentrations were greatest within 60 min of each meal for the NPAA diet, but remained elevated for 3–5 h after the HP diet. The three WL diets showed no difference for either fasting concentrations or the postprandial net incremental AUC (net AUCi) for insulin, ghrelin or PYY. No strong correlations were observed between composite hunger scores and net AUCi for either AA or gut peptides. Regulation of hunger may involve subtle interactions, and a range of signals may need to be integrated to produce the overall response.

Nutrition across the lifespan encompasses both preventative and treatment options to maintain health and vitality. This review will focus on the challenge of overconsumption of energy relative to energy expenditure and the consequent development of overweight and obesity, since they are responsible for much of the burden of chronic disease in the developed world. Understanding the mechanisms of hunger and satiety and how particular foodstuffs and nutrients affect appetite and motivation to eat is important for evidence-based interventions to achieve weight control and design of community-wide dietary strategies that reach across the lifespan. Food reformulation for appetite control and weight management requires a knowledge of the mechanisms of hunger and satiety, how food interacts with peripheral and central regulatory systems, and how these interactions change across the lifecourse, allied to the technical capability to generate, evaluate and develop new ingredients and foods with enhanced biological potency based on these mechanisms. Two European Union-funded research projects, Full4Health and SATIN, are adopting these complementary approaches. These research projects straddle the sometimes conflicted ground between justifiable public health concerns on the one hand and the food and drink industry on the other. These multi-disciplinary projects pull together expertise in nutrition, neuroimaging, psychology and food technology that combines with food industry partners to maximise expected impact of the research. Better knowledge of mechanisms regulating hunger/satiety will lead to evidence base for preventive strategies for the European population, to reduction of chronic disease burden and to increased competitiveness of European food industry through the development of new food products.

To date, no study has directly and simultaneously measured the discrepancy between what people actually eat and what they report eating under observation in the context of energy balance (EB). The present study aimed to objectively measure the ‘extent’ and ‘nature’ of misreporting of dietary intakes under conditions in which EB and feeding behaviour were continuously monitored. For this purpose, a total of fifty-nine adults were recruited for 12 d, involving two 3 d overt phases and two 3 d covert phases of food intake measurement in a randomised cross-over design. Subjects had ad libitum access to a variety of familiar foods. Food intake was covertly measured using a feeding behaviour suite to establish actual energy and nutrient intakes. During the overt phases, subjects were instructed to self-report food intake using widely accepted methods. Misreporting comprised two separate and synchronous phenomena. Subjects decreased energy intake (EI) when asked to record their food intake (observation effect). The effect was significant in women ( − 8 %, P< 0·001) but not in men ( − 3 %, P< 0·277). The reported EI was 5 to 21 % lower (reporting effect) than the actual intake, depending on the reporting method used. Semi-quantitative techniques gave larger discrepancies. These discrepancies were identical in men and women and non-macronutrient specific. The ‘observation’ and ‘reporting’ effects combined to constitute total misreporting, which ranged from 10 to 25 %, depending on the intake measurement assessed. When studied in a laboratory environment and EB was closely monitored, subjects under-reported their food intake and decreased the actual intake when they were aware that their intake was being monitored.

Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m2, took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30 % of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An 18fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n 4) or 4 h after consumption of a test meal (n 8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-13C]acetoacetate, [2,4-13C]3-hydroxybutyrate and [6,6-2H2]glucose. The composite hunger score was 14 % lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P< 0·001). The 9-fold difference in carbohydrate intakes between the HPLC and HPMC dietary interventions led to a 5 % lower supply of glucose to the brain. Despite this, the uptake of glucose by the fifty-four regions of the brain analysed remained similar for the two dietary interventions. In conclusion, differences in the composite hunger score observed for the two dietary interventions are not associated with the use of alternative fuels by the brain.

Dietary strategies that can help reduce hunger and promote fullness are beneficial for weight control, since these are major limiting factors for success. High-protein (HP) diets, specifically those that maintain the absolute number of grams ingested, while reducing energy, are a popular strategy for weight loss (WL) due to the effects of protein-induced satiety to control hunger. Nonetheless, both the safety and efficacy of HP WL diets have been questioned, particularly in combination with low-carbohydrate advice. Nonetheless, for short-to-medium-term intervention studies (over several months), increasing the energetic contribution of protein does appear effective. The effects of HP diets on appetite, bone health, renal function, blood pressure, cardiovascular bio-markers, antioxidant status, gut health and psychological function are discussed. Further research is warranted to validate the physiological effects of HP diets over longer periods of time, including studies that modify the quality of macronutrients (i.e. the type of carbohydrate, fat and protein) and the interaction with other interventions (e.g. exercise and dietary supplements).

There are concerns that weight-loss (WL) diets based on very low carbohydrate (LC) intake have a negative impact on antioxidant status and biomarkers of cardiovascular and metabolic health. Obese men (n 16) participated in a randomised, cross-over design diet trial, with food provided daily, at approximately 8·3 MJ/d (approximately 70 % of energy maintenance requirements). They were provided with two high-protein diets (30 % of energy), each for a 4-week period, involving a LC (4 % carbohydrate) and a moderate carbohydrate (MC, 35 % carbohydrate) content. Body weight was measured daily, and weekly blood samples were collected. On average, subjects lost 6·75 and 4·32 kg of weight on the LC and MC diets, respectively (P < 0·001, sed 0·350). Although the LC and MC diets were associated with a small reduction in plasma concentrations of retinol, vitamin E (α-tocopherol) and β-cryptoxanthin (P < 0·005), these were still above the values indicative of deficiency. Interestingly, plasma vitamin C concentrations increased on consumption of the LC diet (P < 0·05). Plasma markers of insulin resistance (P < 0·001), lipaemia and inflammation (P < 0·05, TNF-α and IL-10) improved similarly on both diets. There was no change in other cardiovascular markers with WL. The present data suggest that a LC WL diet does not impair plasma indices of cardiometabolic health, at least within 4 weeks, in otherwise healthy obese subjects. In general, improvements in metabolic health associated with WL were similar between the LC and MC diets. Antioxidant supplements may be warranted if LC WL diets are consumed for a prolonged period.

The effects of incremental exercise on appetite, energy intake (EI), expenditure (EE) and balance (EB) in lean men and women were examined. Six men (age 29·7 (sd 5·9) years, weight 75·2 (sd 15·3) kg, height 1·75 (sd 0·11) m) and six women (age 24·7 (sd 5·9) years, weight 66·7 (sd 9·10) kg, height 1·70 (sd 0·09) m) were each studied three times during a 16 d protocol, corresponding to no additional exercise (Nex), moderate-intensity exercise (Mex; 1·5–2·0 MJ/d) and high-intensity exercise (Hex; 3·0–4·0 MJ/d) regimens. Subjects were fed to EB during days 1–2, and during days 3–16 they fed ad libitum from a medium-fat diet of constant composition. Daily EE, assessed using the doubly labelled water method, was 9·2, 11·6 and 13·7 MJ/d (P < 0·001; sed 0·45) for the women and 12·2, 14·0 and 16·7 MJ/d (P = 0·007; sed 1·11) for the men on the Nex, Mex and Hex treatments, respectively. EI was 8·3, 8·6 and 9·9 MJ/d (P = 0·118; sed 0·72) for the women and 10·6, 11·6 and 12·0 MJ/d (P = 0·031; sed 0·47) for the men, respectively. On average, subjects compensated for about 30 % of the exercise-induced energy deficit. However, the degree of compensation varied considerably among individuals. The present study captured the initial compensation in EI for exercise-induced energy deficits. Total compensation would take a matter of weeks.