Endogenous biological rhythms synchronise human physiology with daily cycles of light-dark, wake-sleep, feeding-fasting. Proper circadian alignment is crucial for physiological function, reflected in the rhythmic expression of molecular clock genes in various tissues, especially in skeletal muscle. Circadian disruption, such as misaligned feeding, dysregulates metabolism and increases the risk of metabolic disorders like type 2 diabetes. Such disturbances are common in critically ill patients, especially those who rely on enteral nutrition. Whilst continuous provision of enteral nutrition is currently the most common practice in ciritical care, this is largely dictated by convenience rather than evidence. Conversely, some findings indicate that that intermittent provision of enteral nutrition aligned with daylight may better support physiological functions and improve clinical/metabolic outcomes. However, there is a critical need for studies of skeletal muscle responses to acutely divergent feeding patterns, in addition to complementary translational research to map tissue-level physiology to whole-body and clinical outcomes.

The aim of this study was to assess whether adding Ca2+ to aggregate or native forms of β-lactoglobulin alters gut hormone secretion, gastric emptying rates and energy intake in healthy men and women. Fifteen healthy adults (mean ± sd: 9M/6F, age: 24 ± 5 years) completed four trials in a randomised, double-blind, crossover design. Participants consumed test drinks consisting of 30 g of β-lactoglobulin in a native form with (NATIVE + MINERALS) and without (NATIVE) a Ca2+-rich mineral supplement and in an aggregated form both with (AGGREG + MINERALS) and without the mineral supplement (AGGREG). Arterialised blood was sampled for 120 min postprandially to determine gut hormone concentrations. Gastric emptying was determined using 13C-acetate and 13C-octanoate, and energy intake was assessed with an ad libitum meal at 120 min. A protein × mineral interaction effect was observed for total glucagon-like peptide-1 (GLP-1TOTAL) incremental AUC (iAUC; P < 0·01), whereby MINERALS + AGGREG increased GLP-1TOTAL iAUC to a greater extent than AGGREG (1882 ± 603 v. 1550 ± 456 pmol·l−1·120 min, P < 0·01), but MINERALS + NATIVE did not meaningfully alter the GLP-1 iAUC compared with NATIVE (1669 ± 547 v. 1844 ± 550 pmol·l−1·120 min, P = 0·09). A protein × minerals interaction effect was also observed for gastric emptying half-life (P < 0·01) whereby MINERALS + NATIVE increased gastric emptying half-life compared with NATIVE (83 ± 14 v. 71 ± 8 min, P < 0·01), whereas no meaningful differences were observed between MINERALS + AGGREG v. AGGREG (P = 0·70). These did not result in any meaningful changes in energy intake (protein × minerals interaction, P = 0·06). These data suggest that the potential for Ca2+ to stimulate GLP-1 secretion at moderate protein doses may depend on protein form. This study was registered at clinicaltrials.gov (NCT04659902).

A high dose of whey protein hydrolysate fed with milk minerals rich in calcium (Capolac®) results in enhanced glucagon-like peptide-1 (GLP-1) concentrations in lean individuals; however, the effect of different calcium doses ingested alongside protein is unknown. The present study assessed the dose response of calcium fed alongside 25 g whey protein hydrolysate on GLP-1 concentrations in individuals with overweight/obesity. Eighteen adults (mean ± sd: 8M/10F, 34 ± 18 years, 28·2 ± 2·9 kgm−2) completed four trials in a randomised, double-blind, crossover design. Participants consumed test solutions consisting of 25 g whey protein hydrolysate (CON), supplemented with 3179 mg (LOW), 6363 mg (MED) or 9547 mg (HIGH) Capolac® on different occasions, separated by at least 48 h. The calcium content of test solutions equated to 65, 892, 1719 and 2547 mg, respectively. Arterialised-venous blood was sampled over 180 min to determine plasma concentrations of GLP-1TOTAL, GLP-17–36amide, insulin, glucose, NEFA, and serum concentrations of calcium and albumin. Ad libitum energy intake was measured at 180 min. Time–averaged incremental AUC (iAUC) for GLP-1TOTAL (pmol·l−1·min−1) did not differ between CON (23 ± 4), LOW (25 ± 6), MED (24 ± 5) and HIGH (24 ± 6). Energy intake (kcal) did not differ between CON (940 ± 387), LOW (884 ± 345), MED (920 ± 334) and HIGH (973 ± 390). Co-ingestion of whey protein hydrolysate with Capolac® does not potentiate GLP-1 release in comparison with whey protein hydrolysate alone. The study was registered at clinical trials (NCT03819972).

Poor post-prandial glucose control is a risk factor for multiple health conditions. The second-meal effect refers to the progressively improved glycaemic control with repeated feedings, an effect which is achievable with protein ingestion at the initial eating occasion. The most pronounced glycaemic response each day therefore typically occurs following breakfast, so the present study investigated whether ingesting protein during the night could improve glucose control at the first meal of the day. In a randomised crossover design, fifteen adults (seven males, eight females; age, 22 (sd 3) years; BMI, 24·0 (sd 2·8) kg/m2; fasting blood glucose, 4·9 (sd 0·5) mmol/l) woke at 04.00 (sd 1) hours to ingest 300 ml water with or without 63 g whey protein. Participants then completed a mixed-macronutrient meal tolerance test (1 g carbohydrate/kg body mass, 2356 (sd 435) kJ), 5 h 39 min following the nocturnal feeding. Nocturnal protein ingestion increased the glycaemic response (incremental AUC) to breakfast by 43·5 (sd 55·5) mmol × 120 min/l (P = 0·009, d = 0·94). Consistent with this effect, individual peak blood glucose concentrations were 0·6 (sd 1·0) mmol/l higher following breakfast when protein had been ingested (P = 0·049, d = 0·50). Immediately prior to breakfast, rates of lipid oxidation were 0·02 (sd 0·03) g/min higher (P = 0·045) in the protein condition, followed by an elevated post-prandial energy expenditure (0·38 (sd 0·50) kJ/min, P = 0·018). Post-prandial appetite and energy intake were similar between conditions. The present study reveals a paradoxical second-meal phenomenon whereby nocturnal whey protein feeding impaired subsequent glucose tolerance, whilst increasing post-prandial energy expenditure.

Morning coffee is a common remedy following disrupted sleep, yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated. In a randomised crossover design, twenty-nine adults (mean age: 21 (sd 1) years, BMI: 24·4 (sd 3·3) kg/m2) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep (Control; in bed, lights-off trying to sleep approximately 23.00–07.00 hours), the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), with and without morning coffee approximately 1 h after waking (approximately 300 mg caffeine as black coffee 30 min prior to OGTT). Individualised peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (mean (normalised CI) for Control, Fragmented and Fragmented + Coffee, respectively; glucose: 8·20 (normalised CI 7·93, 8·47) mmol/l v. 8·23 (normalised CI 7·96, 8·50) mmol/l v. 8·96 (normalised CI 8·70, 9·22) mmol/l; insulin: 265 (normalised CI 247, 283) pmol/l; and 235 (normalised CI 218, 253) pmol/l; and 310 (normalised CI 284, 337) pmol/l). Likewise, incremental AUC for plasma glucose was higher in the Fragmented + Coffee trial compared with Fragmented. Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed, then a reduction in glucose tolerance can be expected.

This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until ‘comfortably full’ (ad libitum) and on the other, until they ‘could not eat another bite’ (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine–tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.

Hypertensive disorders of pregnancy (HDP) may increase the risk of offspring depression in childhood. Low birth weight is also associated with increased risk of mental health problems, including depression. This study sought to investigate (a) whether there is an association between HDP and the risk of depression in childhood and (b) whether low birth weight mediates this association. The current study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective, population-based study that has followed a cohort of offspring since their mothers were pregnant (n = 6,739). Depression at the age of 7 years was diagnosed using parent reports via the Development and Well-Being Assessment (DAWBA). Log-binomial regression and mediation analyses were used. Children exposed to HDP were 2.3 times more likely to have a depression diagnosis compared with nonexposed children, adjusted Risk Ratio [RR], 2.31; 95% CI, [1.20, 4.47]. Low birth weight was a weak mediator of this association. Results were adjusted for confounding variables including antenatal depression and anxiety during pregnancy.This study suggests that fetal exposure to maternal hypertensive disorders of pregnancy increased the risk of childhood depression. The study adds to the evidence suggesting that the uterine environment is a critical determinant of neurodevelopmental and psychiatric outcomes.

Obesity remains a major public health concern and intermittent fasting is a popular strategy for weight loss, which may present independent health benefits. However, the number of diet books advising how fasting can be incorporated into our daily lives is several orders of magnitude greater than the number of trials examining whether fasting should be encouraged at all. This review will consider the state of current understanding regarding various forms of intermittent fasting (e.g. 5:2, time-restricted feeding and alternate-day fasting). The efficacy of these temporally defined approaches appears broadly equivalent to that of standard daily energy restriction, although many of these models of intermittent fasting do not involve fed-fasted cycles every other 24 h sleep–wake cycle and/or permit some limited energy intake outside of prescribed feeding times. Accordingly, the intervention period therefore may not regularly alternate, may not span all or even most of any given day, and may not even involve absolute fasting. This is important because potentially advantageous physiological mechanisms may only be initiated if a post-absorptive state is sustained by uninterrupted fasting for a more prolonged duration than applied in many trials. Indeed, promising effects on fat mass and insulin sensitivity have been reported when fasting duration is routinely extended beyond sixteen consecutive hours. Further progress will require such models to be tested with appropriate controls to isolate whether any possible health effects of intermittent fasting are primarily attributable to regularly protracted post-absorptive periods, or simply to the net negative energy balance indirectly elicited by any form of dietary restriction.

The present paper reviews the physiological responses of human liver carbohydrate metabolism to physical activity and ingestion of dietary sugars. The liver represents a central link in human carbohydrate metabolism and a mechanistic crux point for the effects of dietary sugars on athletic performance and metabolic health. As a corollary, knowledge regarding physiological responses to sugar ingestion has potential application to either improve endurance performance in athletes, or target metabolic diseases in people who are overweight, obese and/or sedentary. For example, exercise increases whole-body glycogen utilisation, and the breakdown of liver glycogen to maintain blood glucose concentrations becomes increasingly important as exercise intensity increases. Accordingly, prolonged exercise at moderate-to-high exercise intensity results in depletion of liver glycogen stores unless carbohydrate is ingested during exercise. The exercise-induced glycogen deficit can increase insulin sensitivity and blood glucose control, and may result in less hepatic lipid synthesis. Therefore, the induction and maintenance of a glycogen deficit with exercise could be a specific target to improve metabolic health and could be achieved by carbohydrate (sugar) restriction before, during and/or after exercise. Conversely, for athletes, maintaining and restoring these glycogen stores is a priority when competing in events requiring repeated exertion with limited recovery. With this in mind, evidence consistently demonstrates that fructose-containing sugars accelerate post-exercise liver glycogen repletion and could reduce recovery time by as much as half that seen with ingestion of glucose (polymers)-only. Therefore, athletes aiming for rapid recovery in multi-stage events should consider ingesting fructose-containing sugars to accelerate recovery.

Oral glucose tolerance and insulin sensitivity are common measures, but are determined using various blood sampling methods, employed under many different experimental conditions. This study established whether measures of oral glucose tolerance and oral glucose-derived insulin sensitivity (insulin sensitivity indices; ISI) differ when calculated from venous v. arterialised blood. Critically, we also established whether any differences between sampling methods are consistent across distinct metabolic conditions (after rest v. after exercise). A total of ten healthy men completed two trials in a randomised order, each consisting of a 120-min oral glucose tolerance test (OGTT), either at rest or post-exercise. Blood was sampled simultaneously from a heated hand (arterialised) and an antecubital vein of the contralateral arm (venous). Under both conditions, glucose time-averaged AUC was greater from arterialised compared with venous plasma but importantly, this difference was larger after rest relative to after exercise (0·99 (sd 0·46) v. 0·56 (sd 0·24) mmol/l, respectively; P<0·01). OGTT-derived ISIMatsuda and ISICederholm were lower when calculated from arterialised relative to venous plasma and the arterialised–venous difference was greater after rest v. after exercise (ISIMatsuda: 1·97 (sd 0·81) v. 1·35 (sd 0·57) arbitrary units (au), respectively; ISICederholm : 14·76 (sd 7·83) v. 8·70 (sd 3·95) au, respectively; both P<0·01). Venous blood provides lower postprandial glucose concentrations and higher estimates of insulin sensitivity, compared with arterialised blood. Most importantly, these differences between blood sampling methods are not consistent after rest v. post-exercise, preventing standardised venous-to-arterialised corrections from being readily applied.

The aim of this study was to analyse the association between plain water intake and glycated Hb (HbA1c) in the National Diet and Nutrition Survey (2008–2012) rolling survey. These data included diet (4-d diaries) and HbA1c (fasted blood sample) measures of 456 men and 579 women aged 44 (sd 18) years with full information on covariates of interest (age, ethnicity, BMI, smoking status, education, other beverage intake, energy intake and fibre). Data were analysed using sex-stratified linear and logistic regressions modelling the associations of cups per d (240 ml) of plain water with HbA1c, and odds of HbA1c≥5·5 %, respectively. Substitution analyses modelled the replacement of sugar-sweetened beverages, fruit juice and artificially sweetened beverages with plain water. After adjustment, 1 cup/d of plain water was associated with a −0·04 % lower HbA1c (95 % CI −0·07, −0·02) in men. In logistic regression, men had a 22 % (95 % CI 10, 32 %) reduced odds of HbA1c≥5·5 %/cup per d of plain water. There was no evidence of an association with either HbA1c or odds of HbA1c≥5·5 % in women. None of the substitution models was associated with a change in odds of HbA1c≥5·5 %. Plain water intake was associated with lower HbA1c in men but not in women. Substituting water for specific beverages was not associated with a reduced odds of HbA1c≥5·5 %, suggesting that the addition of water is the more pertinent factor. Future trials should test whether the relationships between water intake and HbA1c is causal as this could be a cost-effective and simple health intervention.

Correlation of lower Cambrian strata is often confounded by provincialism of key fauna. The widespread occurrence of the micromollusc Watsonella crosbyi Grabau, 1900 is therefore an important biostratigraphic signpost with potential for international correlation of lower Cambrian successions. Previous correlations of W. crosbyi from Australia (Normanville Group) suggested an Atdabanian- to Botoman-equivalent age. However, in the upper part of the Mount Terrible Formation, stratigraphic ranges of W. crosbyi and Aldanella sp. cf. golubevi overlap prior to the incoming of vertically burrowed ‘piperock’, which is indicative of an age no earlier than Cambrian Stage 2. The stratigraphic range of W. crosbyi in the Normanville Group, South Australia correlates with the ranges of the taxon in China, France, Mongolia and Siberia (though not Newfoundland). The new Australian data add further support for considering the first occurrence of W. crosbyi a good potential candidate for defining the base of Cambrian Stage 2. The stratigraphic range of W. crosbyi through the lower Cambrian Normanville Group has been determined based on collections from measured sections. Although rare, W. crosbyi is part of an assemblage of micromolluscs including Bemella sp., Parailsanella sp. cf. murenica and a sinistral form of Aldanella (A. sp. cf. A. golubevi). Other fauna present include Australohalkieria sp., Eremactis mawsoni, chancelloriids and Cupitheca sp.

The Bath Breakfast Project is a series of randomised controlled trials exploring the effects of extended morning fasting on energy balance and health. These trials were categorically not designed to answer whether or not breakfast is the most important meal of the day. However, this review will philosophise about the meaning of that question and about what questions we should be asking to better understand the effects of breakfast, before summarising how individual components of energy balance and health respond to breakfast v. fasting in lean and obese adults. Current evidence does not support a clear effect of regularly consuming or skipping breakfast on body mass/composition, metabolic rate or diet-induced thermogenesis. Findings regarding energy intake are variable, although the balance of evidence indicates some degree of compensatory feeding later in the day such that overall energy intake is either unaffected or slightly lower when breakfast is omitted from the diet. However, even if net energy intake is reduced, extended morning fasting may not result in expected weight loss due to compensatory adjustments in physical activity thermogenesis. Specifically, we report that both lean and obese adults expended less energy during the morning when remaining in the fasted state than when consuming a prescribed breakfast. Further research is required to examine whether particular health markers may be responsive to breakfast-induced responses of individual components of energy balance irrespective of their net effect on energy balance and therefore body mass.

Breakfast omission is associated with obesity and CVD/diabetes, but the acute effects of extended morning fasting upon subsequent energy intake and metabolic/hormonal responses have received less attention. In a randomised cross-over design, thirty-five lean men (n 14) and women (n 21) extended their overnight fast or ingested a typical carbohydrate-rich breakfast in quantities relative to RMR (i.e. 1963 (sd 238) kJ), before an ad libitum lunch 3 h later. Blood samples were obtained hourly throughout the day until 3 h post-lunch, with subjective appetite measures assessed. Lunch intake was greater following extended fasting (640 (sd 1042) kJ, P< 0·01) but incompletely compensated for the omitted breakfast, with total intake lower than the breakfast trial (3887 (sd 1326) v. 5213 (sd 1590) kJ, P< 0·001). Systemic concentrations of peptide tyrosine–tyrosine and leptin were greater during the afternoon following breakfast (both P< 0·05) but neither acylated/total ghrelin concentrations were suppressed by the ad libitum lunch in the breakfast trial, remaining greater than the morning fasting trial throughout the afternoon (all P< 0·05). Insulin concentrations were greater during the afternoon in the morning fasting trial (all P< 0·01). There were no differences between trials in subjective appetite during the afternoon. In conclusion, morning fasting caused incomplete energy compensation at an ad libitum lunch. Breakfast increased some anorectic hormones during the afternoon but paradoxically abolished ghrelin suppression by the second meal. Extending morning fasting until lunch altered subsequent metabolic and hormonal responses but without greater appetite during the afternoon. The present study clarifies the impact of acute breakfast omission and adds novel insights into second-meal metabolism.

We investigated an outbreak of infection in 10 patients with blood cultures positive for B. cepacia. All patients had indwelling intravenous catheters. Though we did not identify the source of the organism, our findings support the hypothesis that cross-contamination of multidose medications through the use of the same needle and syringe was a contributing factor.