Liver injury is an independent risk factor for multiple organ dysfunction and high mortality in patients with sepsis. However, the pathological mechanisms and therapeutic strategies for sepsis-associated liver injury have not been fully elucidated. Time-restricted feeding (TRF) is a promising dietary regime, but its role in septic liver injury remains unknown. Using 16S rRNA gene sequencing, Q200 targeted metabolomics, transcriptomics, germ-free mice, Hmgcs2/Lpin1 gene knockout mice, and Aml12 cells experiments, we revealed that TRF can mitigate septic liver injury by modulating the gut microbiota, particularly by increasing Lactobacillus murinus (L. murinus) abundance, which was significantly reduced in septic mice. Further study revealed that live L. murinus could markedly elevate serum levels of metabolite 3-hydroxybutyrate (3-HB) and alleviate sepsis-related injury, while the knockout of the key enzyme for 3-HB synthesis (3-hydroxy-3-methylglutaryl-CoA synthase 2, Hmgcs2) in the liver negated this protective effect. Additionally, serum 3-HB levels were significantly positively correlated with L. murinus abundance and negatively correlated with liver injury indicators in septic patients, demonstrating a strong predictive value for septic liver injury (AUC = 0.8429). Mechanistically, 3-HB significantly inhibited hepatocyte ferroptosis by activating the PI3K/AKT/mTOR/LPIN1 pathway, reducing ACSL4, MDA, LPO, and Fe2+ levels. This study demonstrates that TRF reduces septic liver injury by modulating gut microbiota to increase L. murinus, which elevates 3-HB to activate PI3K/AKT/mTOR/LPIN1 and inhibit hepatocyte ferroptosis. Overall, this study elucidates the protective mechanism of TRF against septic liver injury and identifies 3-HB as a potential therapeutic target and predictive biomarker, thereby providing new insights into the clinical management and diagnosis of septic liver injury.

Type 2 Diabetes Mellitus (T2DM) represents a major global health issue, with its incidence anticipated to increase markedly in the forthcoming decades. Efficient non-pharmacological therapies, especially dietary approaches, are essential for regulating glycemic control and facilitating weight reduction. Intermittent Fasting (IF) and Continuous Caloric Restriction (CCR) are two well researched methodologies, but their relative effectiveness and enduring advantages continue to be topics of active discussion. This review systematically assesses and contrasts the impacts of intermittent fasting (IF) and continuous calorie restriction (CCR) on glycemic regulation and weight reduction in persons with type 2 diabetes mellitus (T2DM), highlighting their short-term and long-term effects, safety profiles, and adherence rates. A thorough literature analysis was performed utilizing PubMed and Google Scholar, concentrating on papers published from 2000 to 2024. The review encompassed randomized controlled trials and observational studies that investigated the effects of intermittent fasting (IF) and continuous calorie restriction (CCR) on glycemic indicators (HbA1c, fasting glucose) and body weight. IF shown substantial short-term advantages, encompassing marked decreases in HbA1c levels, fasting glucose, and body weight. Mechanistic discoveries emphasized better insulin sensitivity, augmented fat metabolism, and autophagy as key aspects. In contrast, CCR was linked to enduring metabolic enhancements, including decreased visceral fat and improved insulin sensitivity. Nevertheless, both dietary approaches demonstrated constraints.

This meta-analysis aimed to determine the short- (< 3 months) and long-term (≥ 3 months) metabolic effects of IF in patients with type 2 diabetes. We hypothesized that IF is non-inferior to other dietary control methods (including continuous energy restriction, standard diet, Mediterranean diet and ad libitum diet) in terms of both short-term and long-term metabolic impacts in patients with type 2 diabetes. We searched for studies in the MEDLINE, EMBASE, and Cochrane Library until August 20, 2023. Studies with non-type 2 diabetes patients, interventions other than IF, no control group, or non-randomized clinical trial designs were excluded. A meta-analysis was then conducted with a random effects model. The Risk of Bias was assessed using the Cochrane risk-of-bias tool (ROB 2). 12 articles with a total of 966 participants were included. IF significantly decreased glycated hemoglobin A1c (HbA1c) (standardized mean difference [SMD]: -0.93; 95% confidence interval [CI]: -1.64, -0.22; P = 0.01), fasting plasma glucose (FPG) (SMD: -0.73; 95% CI: -0.92, -0.54; P < 0.00001) and body weight (SMD: -1.11; 95% CI: -1.92, -0.31; P = 0.007) in the short term compared to control interventions, but showed a similar effect to control interventions in the long term. Substantial heterogeneity existed among our studies. Over the intervention period, long-term IF may safely and feasibly help patients with type 2 diabetes effectively manage blood sugar and reduce body weight, but the metabolic benefits of IF don't endure after its discontinuation. Therefore, continual long-term IF may provide more lasting metabolic benefits.

Time-restricted eating (TRE) may extend the cardiometabolic health benefits of calorie restriction (CR). However, few studies have compared its effect on the circadian regulation of glucose metabolism and the optimal time of day to initiate TRE is also unclear. This study aims to compare the effectiveness of CR with and without TRE on glucose tolerance in response to 3 identical meals consumed over the day. A parallel, single-blinded, 3-arm randomised controlled trial will be conducted in 114 adults, aged 35 to 75 years with a BMI ≥25.1 but <45.0 kg/m2, elevated waist circumference and fasting blood glucose (≥5.6 mmol/L), and who score ≥12 on the Australian Type 2 Diabetes Risk Assessment tool. Participants will be stratified by sex and fasting blood glucose (≤6.0 mmol/L; >6.0 mmol/L) and then randomised (1:1:1) to CR (unrestricted meal timing), eCR (0800 to 1600) or dCR (1200-2000) for 8 weeks. The primary outcome is the change in the natural logarithm of the mean over 3 identical meals of the postprandial glucose area under the curve (AUC). The analysis will be performed using a covariate adjusted linear regression of the differences in postprandial glucose log AUC at 8 weeks from baseline. This randomised clinical trial will be the first to delineate the benefits of CR alone or in combination with time restricted eating on postprandial glucose metabolism over the day in adults at increased risk of type 2 diabetes.

Autophagy slows age-related pathologies and is stimulated by nutrient restriction in animal studies. However, this has never been shown in humans. We measured autophagy using a physiologically relevant measure of autophagic flux (flux of MAP1LC3B isoform II/LC3B-II in peripheral blood mononuclear cells in the context of whole blood) in 121 humans with obesity who were randomised to standard care (SC, control condition), calorie restriction (CR) or intermittent fasting plus time-restricted eating (iTRE) for 6 months. While the differences in change from baseline between groups was not significant at 2 months, we observed a significant difference in change from baseline between iTRE compared to SC at 6 months (P = 0.04, post hoc analysis). This effect may be driven partly by a tendency for autophagy to decrease in the SC group. The difference in change from baseline between CR and SC was not significant. Uncorrected analysis of correlations showed a negative relationship between change in autophagy and change in blood triglycerides. Data on the specificity and performance of the methods used to measure human autophagy are also presented. This shows autophagy may be increased by intermittent nutrient restriction in humans. If so, this is a demonstration that nutrient restriction can be used to improve a primary hallmark of biological ageing and provides a mechanism for how fasting could delay the onset of age-related disease. KEY POINTS: Autophagy slows biological ageing, and dysfunction of autophagy has been implicated in age-related disease - an effective way of increasing autophagy in cells and animal models is nutrient restriction. However, the impact of different types of nutrient restriction on physiological autophagic flux in humans has not been extensively researched. Here we measure the effect of intermittent time-restricted eating (iTRE) and calorie restriction on physiological autophagic flux in peripheral blood mononuclear cells. After 6 months, there was a significant difference in change from baseline between the iTRE and the standard care control group, with flux being higher in the iTRE group at this timepoint. However, there was no significant increase from baseline within the iTRE group, showing that although autophagy may be modified by nutrient restriction in humans, further studies are required.

Time-restricted eating (TRE) is a type of intermittent fasting, requiring individuals to limit their eating timeframe to specific hours in the day, while maintaining a fasting period greater than 12 h. Fat oxidation (FOx) is a critical determinant in the pathophysiology of metabolic diseases, with impaired FOx contributing to conditions such as insulin resistance and obesity, whereas enhanced FOx is associated with improved metabolic health. However, the impact of the 16:8 TRE model on FOx remains largely unexplored. The aim of this study was to determine the effect of a 6-week TRE on resting and exercise substrate oxidation, body composition, and blood markers related to metabolic health.

Thirty-three healthy, young males (age: 27.5 ± 6 years, body mass: 76.5 ± 8.4 kg, maximal oxygen uptake [V˙O2max]: 43.9 ± 6.6 mL·kg-1·min-1) were assigned to either TRE (n = 16) or control group (n = 17), with efforts to match baseline characteristics, including V˙O2max and body composition. The TRE group followed a 16:8 program for 6 weeks, while controls maintained their existing dietary habits. Body composition, blood glucose, insulin, blood lipids, resting substrate oxidation, and FOx during cycling at 40 % V˙O2max were assessed before and after the 6-week period. Data were analyzed using both intention-to-treat (ITT) and per-protocol approaches.

Thirty-three participants were included in the ITT analysis, while 31 participants were included in the per-protocol analysis. Compared to baseline, results showed a significant difference (p < 0.05) between TRE and control groups in body mass (TRE versus control) (Δ = -2.8 kg versus Δ = 0.7 kg), fat mass (Δ = -1.4 kg versus Δ = 0.4 kg), percent body fat (-1.7 % versus 0.4 %), lean mass (Δ = -1.4 kg versus Δ = 0.3 kg), and visceral adipose tissue mass (Δ = -39.7 g versus Δ = 46.4 g). There was a significant difference between TRE and control groups in resting respiratory exchange ratio (RER, Δ = -0.02 versus Δ = 0.02; p = 0.016), FOx (Δ = 0.33 mg·kg FFM-1·min-1versus Δ = -0.37 mg·kg FFM-1·min-1; p = 0.007), and carbohydrate oxidation (Δ = -0.39 mg·kg FFM-1·min-1versus Δ = 0.45 mg·kg FFM-1·min-1; p = 0.037) after the 6-week period. Exercise substrate oxidation and fasting blood glucose, insulin, triglycerides, total cholesterol, and high-density lipoprotein cholesterol did not significantly change over time in either group (p > 0.05).

In summary, a 6-week TRE significantly reduces body mass, fat mass, and resting RER as well as increases resting FOx in young, healthy males. However, it does not affect blood markers related to cardiometabolic health or exercise substrate oxidation. This trial was registered at https://clinicaltrials.gov/study/NCT06498102asNCT06498102.

Time-restricted feeding (TRF) holds promise for alleviating cognitive decline in aging, albeit the precise mechanism via the gut-brain axis remains elusive. In a clinical trial, we observed, for the first time, that a 4-month TRF ameliorated cognitive impairments among Alzheimer's disease (AD) patients. Experiments in 5xFAD mice corroborated the gut microbiota-dependent effect of TRF on mitigating cognitive dysfunction, amyloid-beta deposition, and neuroinflammation. Multi-omics integration linked Bifidobacterium pseudolongum (B. pseudolongum) and propionic acid (PA) with key genes in AD pathogenesis. Oral supplementation of B. pseudolongum or PA mimicked TRF's protective effects. Positron emission tomography imaging confirmed PA's blood-brain barrier penetration, while knockdown of the free fatty acid receptor 3 (FFAR3) diminished TRF's cognitive benefits. Notably, we observed a positive correlation between fecal PA and improved cognitive function in an AD cohort, further indicating that TRF enhanced PA production. These findings highlight the microbiota-metabolites-brain axis as pivotal in TRF's cognitive benefits, proposing B. pseudolongum or PA as potential AD therapies.

Intermittent fasting (IF) and ketogenic diets (KDs) have recently attracted much attention in the scientific literature and in popular culture and follow a longer history of exercise and caloric restriction (CR) research. Whereas IF involves cyclic metabolic switching (CMS) between ketogenic and non-ketogenic states, KDs and CR may not. In this Perspective, I postulate that the beneficial effects of IF result from alternating between activation of adaptive cellular stress response pathways during the fasting period, followed by cell growth and plasticity pathways during the feeding period. Thereby, I establish the cyclic metabolic switching (CMS) theory of IF. The health benefits of IF may go beyond those seen with continuous CR or KDs without CMS owing to the unique interplay between the signalling functions of the ketone β-hydroxybutyrate, mitochondrial adaptations, reciprocal activation of autophagy and mTOR pathways, endocrine and paracrine signalling, gut microbiota, and circadian biology. The CMS theory may have important implications for future basic research, clinical trials, development of pharmacological interventions, and healthy lifestyle practices.

Dietary interventions, particularly intermittent fasting (IF) and energy restriction (ER), have emerged as effective strategies for managing weight.

We aimed to conduct a systematic review and meta-analysis exploring the effects of IF and ER on body weight and cardiometabolic factors.

PRISMA compliant methods were used, and PubMed and the Cochrane CENTRAL Library were systematically searched for relevant randomized controlled trials (RCTs) from database inception to September 27, 2023. A bibliographic and gray literature search was also performed to identify unpublished literature. Effect sizes were pooled with random effects models in the R package "meta" and are reported as mean differences with 95 % confidence intervals. The quality of the included studies was assessed with The Cochrane Risk of Bias assessment tool.

A total of 2931 records were identified through a database search. The study included 17 publications: 16 RCTs identified after two stages of screening and an additional publication identified from a bibliographic search. All trials were published between 2011 and 2022, and included a total of 1258 participants (24-209 per study). Pooled analysis revealed that IF led to a more significant decrease in BMI than ER (-0.44 [-0.88 to -0.01]; p < 0.01). Additionally, IF resulted in a slightly greater, but statistically nonsignificant, decrease in weight, triglyceride levels, fasting plasma glucose, and diastolic blood pressure than ER. However, similar decreases in SBP, LDL, and HDL levels were observed between IF and ER, which showed no major differences. The ER group experienced a higher frequency of headaches than the IF group, whereas the IF group reported a greater occurrence of dizziness than the ER group.

IF appears to be slightly advantageous over ER in terms of body weight, cardiometabolic factors, and plasma glucose levels.

Intermittent fasting (IF) is a diet strategy with alternate intervals of calorie reduction and normal eating. Despite its beneficial effects on weight loss and cardiometabolic risk factors, the effect of IF on liver function tests (LFTs) remains unclear.

This study aimed to investigate the effect of IF on LFTs through a systematic review and meta-analysis of randomized clinical trials.

An electronic search was performed using predefined search terms in databases including PubMed, Scopus, and ISI Web of Science until February 2023.

The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for the randomized controlled trials.

The results of this study are reported as weighted mean differences (WMDs) with 95% CIs. Fourteen RCTs were included in the meta-analysis, with a total sample size of 908. IF significantly reduced alanine aminotransferase (ALT) (WMD: -2.88, 95% CI: -4.72 to -1.04, P-value = .002) and aspartate aminotransferase (AST) levels (WMD: -1.67, 95% CI: -3.12 to -0.22, P-value = .024). The results of the subgroup analysis showed that the impact of IF was significant in both the nonalcoholic fatty liver disease and the healthy groups for ALT. The effects of IF on the serum gamma-glutamyl transpeptidase (GGT) level were significant (WMD: -3.19, 95% CI: -6.00 to -0.39, P-value = .026), but there were no significant changes in the alkaline phosphatase (ALP) level (WMD: 1.06, 95% CI: -0.23 to 2.34, P-value = .106). Furthermore, no substantial heterogeneity between studies was reported.

IF can improve ALT, AST, and GGT levels but not ALP enzyme levels and may have a benefit on liver function.

PROSPERO registration no. CRD42023396211.

Intermittent fasting (IF) has been demonstrated to enhance human health through several mechanisms. However, it is still unclear whether those health benefits are independent of caloric restriction (CR)-induced weight loss. This systematic review and meta-analysis aimed to compare isocaloric IF and CR regarding anthropometric measurements, adherence, metabolic profile, inflammatory biomarkers, and adipokines in adults and elderlies.

Comprehensive research was conducted usin four major databases including Embase, PubMed, Scopus, and Google Scholar without date restriction. Mean differences of the change from baseline ± change SD were calculated as the differences between IF and CR groups. Subgroup analysis was performed according to intervention duration (short-, medium-, and long-term). To determine the reliability of our findings, GRADE assessment was performed. As a result, 20 RCTs were included in this systematic review and meta-analysis. IF groups had significant reductions in fat mass (kg) (P = 0.006) and Interleukin-6 (P < 0.00001) in the short term and fat mass (%) (P = 0.0002), waist circumference (P = 0.005), fasting blood insulin (P < 0.00001) and HOMA-IR (P = 0.04) in the long term. CR groups had significantly lower hunger (P = 0.003), fatigue (P = 0.04), and TG (P = 0.03).

IF may be an effective alternative to CR but is not superior to CR in enhancing human health. Due to the low number of long-term studies, future studies should focus on conducting longitudinal randomized trials comparing IF and CR in different populations, age groups, and IF patterns.

A balanced diet is essential for maintaining human health. Increasing evidence suggests that dietary and nutritional interventions contribute to disease management and are associated with reduced healthcare costs and economic burden. Ferroptosis, a novel type of regulated cell death (RCD) driven by lipid peroxidation, has been shown to be involved in various pathological conditions, including diabetes, ischemia/reperfusion (I/R) injury, inflammation-related diseases, and cancer. Therefore, specifically targeting the uncontrolled ferroptosis process may offer new therapeutic opportunities. Of note, certain interventions, such as small-molecule compounds, natural products, herbal medicines, and non-pharmacological approaches, have been reported to prevent and treat multiple human diseases by reversing the dysregulation of ferroptosis. In this review, we present the key molecular mechanisms that regulate ferroptosis. Importantly, interventions targeting ferroptosis are summarized from the perspective of dietary patterns, food and nutrients. By understanding these advances, innovative ideas can be provided for individualized dietary interventions and treatment strategies.

The risk factors for type 2 diabetes mellitus (T2DM) have been increasingly researched, but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors, which are categorized in this paper into five categories: Social determinants, lifestyle, checkable/testable risk factors, history of illness and medication, and other factors, which are discussed in a narrative review. Meanwhile, this paper points out the problems of the current research, helps to improve the systematic categorisation and practicality of T2DM risk factors, and provides a professional research basis for clinical practice and industry decision-making.

Pancreatic β-cells are specialized in secreting insulin in response to circulating nutrients, mainly glucose. Diabetes is one of the most prevalent endocrine-metabolic diseases characterized by an imbalance in glucose homeostasis, which result mainly from lack of insulin production (type 1 diabetes) or insufficient insulin and peripheral insulin resistance (type 2 diabetes), both influenced by genetic and environmental components. Pancreatic β-cell dysfunction and islet inflammation are common characteristics of both types of the disease. Pancreatic islets are a highly innervated tissue whose function can be influenced by the brain, either directly through the autonomic nervous system or indirectly via neuroendocrine mechanisms. In addition, it is well-established that there is a fine-tuned communication between the immune and neuroendocrine tissues in maintaining endocrine pancreas homeostasis. Various psycho-social, physico-chemical and lifestyle environmental factors have been associated with diabetes risk. In this review, I briefly comment on certain aspects of the psycho-neuro-immune interactions that link environmental factors and the endocrine pancreas, leading to metabolic health or diabetes. Interdisciplinary research, embracing new and broader perspectives, should be conducted to explore strategies for preventing or slowing down the constant increase in diabetes worldwide.

Breakfast is often termed the most important meal of the day. However, its importance to acute and chronic adaptations to exercise is currently not well summarized throughout the literature.

A narrative review of the experimental literature regarding breakfast consumption's impact on acute and chronic exercise performance and alterations in body composition prior to November 2024 was conducted. To be included in this review, the selected investigations needed to include some aspect of either endurance or resistance training performance and be conducted in humans.

These findings suggest that breakfast consumption may benefit acute long-duration (>60 min) but not short-duration (<60 min) morning endurance exercise. Evening time trial performance was consistently inhibited following breakfast omission despite the resumption of eating midday. No or minimal impact of breakfast consumption was found when examining acute morning or afternoon resistance training or the longitudinal adaptations to either resistance or endurance training. Favorable changes in body composition were often noted following the omission of breakfast. However, this was primarily driven by the concomitant reduced kilocalorie intake.

Consuming breakfast may aid endurance athletes regularly performing exercise lasting >60 min in length. However, the morning meal's impact on resistance training and changes in body composition appears to be minimal. Although, as the body of literature is limited, future investigations are needed to truly ascertain the dietary practice's impact.

Intermittent fasting (IF) can be an effective dietary therapy for weight loss and improving cardiometabolic health. However, there is scant evidence regarding the role of IF on indicators of liver function, particularly in adults with metabolic disorders. Therefore, we performed a systematic review and meta-analysis to investigate the effects of IF on liver function in adults with metabolic disorders.

Three primary electronic databases including PubMed, Web of Science, and Scopus, were searched from inception to September 2024 to identify original studies that used IF interventions with or without control groups in adults with metabolic disorders. Inclusion criteria were (1) studies of human participants with metabolic diseases, (2) interventions that evaluated the effects of IF, (3) with or without a control group, and (4) measured liver fat, liver steatosis, liver fibrosis, or liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as primary outcomes. Standardized mean differences (SMD) and 95% confidence intervals were calculated using random effects models. Heterogeneity was assessed using the Cochran's Q statistic and I-squared statistic (I2). Publication bias was assessed using the visual inspection of funnel plots and Egger's tests. The risk of bias was assessed using the PEDro scale and the NIH quality assessment tool.

A total 21 studies involving 1,226 participants with metabolic disorders were included in the meta-analysis. Overall, IF effectively decreased liver fat with a large effect size [SMD: -1.22 (95% CI: -1.63 to -0.80), p = 0.001], liver steatosis with a medium effect size [SMD: -0.73 (95% CI: -1.12 to -0.35), p = 0.001], ALT with a small effect size [SMD: -0.44 (95% CI: -0.58 to -0.30), p = 0.001], and AST with a small effect size [SMD: -0.30 (95% CI: -0.49 to -0.11), p = 0.001], but not liver fibrosis [SMD: -0.28 (95% CI: -0.59 to 0.02), p = 0.07]. Subgroup analyses showed that IF decreased liver fat and ALT significantly, independent of IF mode, participant age, health status, weight status, and intervention duration. IF significantly decreased liver fibrosis in those with obesity; and decreased AST following 5:2 diets, in middle-aged adults, adults with obesity, and regardless of health status or intervention duration.

IF seems to be an effective dietary therapy for improving liver function in adults with metabolic disorders, and many of liver function-related benefits occur regardless of IF mode, intervention duration, or participant health status.

Significant heterogeneity, small numbers of studies and inclusion of non-randomized trials or single-group pre-post trials were the main limitation of our meta-analysis. Further randomized clinical trials are needed to elucidate the effects of IF on liver function in adults with metabolic disorders.

Early time-restricted eating (eTRE) is a dietary strategy that restricts caloric intake to the first 6-8 h of the day and can effect metabolic benefits independent of weight loss. However, the extent of these benefits is unknown. We conducted a randomized crossover feeding study to investigate the weight-independent effects of eTRE on glycemic variation, multiple time-in-range metrics, and levels of inflammatory markers. Ten adults with prediabetes were randomized to eTRE (8-h feeding window, 80% of calories consumed before 14:00 h) or usual feeding (50% of calories consumed after 16:00 h) for 1 week followed by crossover to the other schedule. Using continuous glucose monitoring, we showed that eTRE decreased glycemic variation (mean amplitude of glycemic excursion) and time in hyperglycemia greater than 140 mg/dL without affecting inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). These data implicate eTRE as a candidate dietary intervention for the weight-independent management of dysglycemia in high-risk individuals.

Different intermittent fasting (IF) protocols have been proven to be efficient in improving cardiometabolic markers, but further research is needed to examine whether or not combining IF regimens plus physical exercise is superior to control diets (ie, nonfasting eating) plus physical exercise in this setting.

The aim of this study was to determine whether or not combining IF plus exercise interventions is more favorable than a control diet plus exercise for improving cardiometabolic health outcomes.

PubMed, Scopus, and Web of Science were comprehensively searched until April 2023.

Electronic databases were searched for clinical trials that determined the effect of IF plus exercise vs a control diet plus exercise on body weight, lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol), and systolic and diastolic blood pressure (SBP and DBP, respectively). Analyses were conducted for IF plus exercise vs a nonfasting diet plus exercise to calculate weighted mean differences (WMDs).

The meta-analysis included a total of 14 studies, with a total sample of 360 adults with or without obesity. The duration ranged from 4 to 52 weeks. IF plus exercise decreased body weight (WMD = -1.83 kg; P = 0.001), LDL (WMD = -5.35 mg/dL; P = 0.03), and SBP (WMD = -2.99 mm Hg; P = 0.003) significantly more than a control diet plus exercise. HDL (WMD = 1.57 mg/dL; P = 0.4) and total cholesterol (WMD = -2.24 mg/dL; P = 0.3) did not change significantly for IF plus exercise vs a control diet plus exercise, but there was a trend for reducing triglycerides (WMD = -13.13 mg/dL; P = 0.07) and DBP (WMD = 2.13 mm Hg; P = 0.05), which shows clinical magnitude.

IF plus exercise improved some cardiometabolic outcomes (body weight, blood pressure, and lipid profile) compared with a control diet plus exercise.

PROSPERO registration no. CRD42023423878.

Closed-loop control systems for precise control of therapeutic gene expression are promising candidates for personalized treatment of chronic ailments such as diabetes. Pancreatic iβ-cells are engineered with blue-light-inducible melanopsin to drive rapid insulin release by vesicular secretion from intracellular stores. In this work, a glucose-operated widget (GLOW) is designed as a component of a closed-loop control system for diabetes treatment by employing a probe that emits blue fluorescence in a glucose-concentration-dependent manner as a real-time glucose sensor to precisely control insulin release from these iβ-cells. As proof-of-concept of the complete control system, the probe is encapsulated together with iβ-cells in alginate-poly-(L-lysine) hydrogel-microbeads(400 µm in diameter and containing about 500 cells) called GLOWiβ (GLOW with iβ-cells), are subcutaneously implanted into type-1-diabetic (T1D) mice. Illumination by UV-A light at 390 nm results in glucose-concentration-dependent blue-light emission from the probe at 445 nm that in turn induces glucose-concentration-dependent insulin release from the iβ-cells in a fully reversible manner. Activation of the injected GLOWiβ at 390 nm for 15 min effectively restores normoglycemia within 60-120 min in a closed-loop manner in these diabetic mice. The system is robust, as normoglycemia is well maintained by daily activation for at least 7 days.

Intermittent fasting (IF) refers to periodic fasting routines, that caloric intake is minimized not by meal portion size reduction but by intermittently eliminating ingestion of one or several consecutive meals. IF can instigate comprehensive and multifaceted alterations in energy metabolism, these metabolic channels may aboundingly function as primordial mechanisms that interface with the immune system, instigating intricate immune transformations. This review delivers a comprehensive understanding of IF, paying particular attention to its influence on the immune system, thus seeking to bridge these two research domains. We explore how IF effects lipid metabolism, hormonal levels, circadian rhythm, autophagy, oxidative stress, gut microbiota, and intestinal barrier integrity, and conjecture about the mechanisms orchestrating the intersect between these factors and the immune system. Moreover, the review includes research findings on the implications of IF on the immune system and patients burdened with autoimmune diseases.

To assess the impact of intermittent fasting, with or without probiotic supplementation, versus a calorie-restricted diet on anthropometric measures, metabolic status and gonadal variables in women with polycystic ovary syndrome (PCOS).

This is a randomized, placebo-controlled, parallel-arm clinical trial. The effects of the 14:10 early time-restricted eating (eTRE) strategy alone or combined with probiotics, on obese women with PCOS, were investigated. Participants were divided into three groups: eTRE plus probiotics (n = 30), eTRE plus placebo (n = 30) and a control group following a standard three-meal-per-day diet with daily calorie restriction (DCR) (n = 30). Over 8 weeks, various anthropometric, metabolic, menstrual and gonadal variables were assessed.

A total of 90 individuals were included in the study, with a mean body weight of 81.4 kg, and a mean age of 30 years. Mean (standard deviation) weight loss was not different between the groups at week 8 (TRE + probiotic: -2.2 [1.6] kg vs. TRE + placebo: -2.9 [2.7] kg vs. DCR: -2.5 [1.7] kg). Results revealed that, while all three regimes led to reductions in body weight, body mass index, vascular risk indicators, hirsutism and acne scores, there were no statistically significant differences between the eTRE groups and the control group in terms of weight loss, or improvements in metabolic, menstrual and gonadal variables (P > .05). Additionally, combining probiotics with eTRE did not benefit hormonal and cardiometabolic factors (P > .05).

The eTRE alone or eTRE plus probiotics did not result in significantly greater weight loss or improvements in metabolic, menstrual and gonadal variables compared with the standard three-meal DCR diet.

Intermittent fasting (IF) modifies cell- and tissue-specific immunometabolic responses that dictate metabolic flexibility and inflammation during obesity and type 2 diabetes (T2D). Fasting forces periods of metabolic flexibility and necessitates increased use of different substrates. IF can lower metabolic inflammation and improve glucose metabolism without lowering obesity and can influence time-dependent, compartmentalized changes in immunity. Liver, adipose tissue, skeletal muscle, and immune cells communicate to relay metabolic and immune signals during fasting. Here we review the connections between metabolic and immune cells to explain the divergent effects of IF compared with classic caloric restriction (CR) strategies. We also explore how the immunometabolism of metabolic diseases dictates certain IF outcomes, where the gut microbiota triggers changes in immunity and metabolism during fasting.

Type 2 diabetes poses significant global health challenges, affecting both the quality of life and healthcare systems. This systematic review evaluates the efficacy of fasting and fasting-mimicking diets (FMD) in managing type 2 diabetes, with a focus on their effects on glycemic control, lipid profiles, and overall metabolic health in adult patients. A comprehensive search of PubMed and Cochrane Library databases identified several studies utilizing various fasting protocols, including intermittent fasting and FMD. Data synthesis and bias assessment were conducted using established methodologies, including the Cochrane Risk of Bias 2 (RoB 2) tool. The review found that fasting interventions significantly improve glycemic control and reduce body weight, with some protocols notably lowering HbA1c levels (p<0.05), highlighting the strong potential of fasting in diabetes management. However, the results varied, suggesting that individual differences in metabolic responses and adherence levels influence outcomes. In conclusion, while fasting and FMD show promise for improving metabolic health and managing diabetes, more standardized research is needed to understand the underlying mechanisms, optimize protocols, and confirm long-term benefits. Future research should prioritize larger sample sizes and extended follow-up periods to inform comprehensive clinical practice guidelines.

To update the evidence of lifestyle interventions for the prevention of type 2 diabetes mellites (T2DM) in adults, particularly in the Asia Pacific region. The key questions to ask are: 1) How effective are lifestyle interventions in preventing T2DM among at-risk adults in the Asia Pacific Region? 2)What are the key characteristics of the implementation of lifestyle interventions for diabetes prevention?

Lifestyle interventions for the prevention of T2DM have been suggested to be effective. There is evidence of ethnic differences in some glycaemic and anthropometric outcomes. The meta-analysis suggested a significant result in reducing waist circumference (standardised mean difference - 019, 95%CI ( -0.31, -0.06)), and no significant effects in other outcomes. However, the implementation outcomes suggested lifestyle intervention might be a cost-effective and sustainable approach in T2DM particularly in countries in the Asia Pacific Region. The focus of lifestyle intervention in the Asia Pacific Region should not only lie in the effectiveness of the trial but a thorough evaluation of the implementation outcomes, as well as cultural adaptations, with the support of all stakeholders through all stages of the implementation.

To perform a meta-analysis to investigate the effects of intermittent fasting (IF), as compared with either a control diet (CON) and/or calorie restriction (CR), on body composition and cardiometabolic health in individuals with prediabetes and type 2 diabetes (T2D).

PubMed, Web of Science, and Scopus were searched from their inception to March 2024 to identify original randomized trials with parallel or crossover designs that studied the effects of IF on body composition and cardiometabolic health. Weighted mean differences (WMDs) or standardized mean differences with 95% confidence intervals (CIs) were calculated using random-effects models.

Overall, 14 studies involving 1101 adults with prediabetes or T2D were included in the meta-analysis. IF decreased body weight (WMD -4.56 kg [95% CI -6.23 to -2.83]; p = 0.001), body mass index (BMI; WMD -1.99 kg.m2 [95% CI -2.74 to -1.23]; p = 0.001), glycated haemoglobin (HbA1c; WMD -0.81% [95% CI -1.24 to -0.38]; p = 0.001), fasting glucose (WMD -0.36 mmol/L [95% CI -0.63 to -0.09]; p = 0.008), total cholesterol (WMD -0.31 mmol/L [95% CI -0.60 to -0.02]; p = 0.03) and triglycerides (WMD -0.14 mmol/L [95% CI -0.27 to -0.01]; p = 0.02), but did not significantly decrease fat mass, insulin, low-densitiy lipoprotein, high-density lipoprotein, or blood pressure as compared with CON. Furthermore, IF decreased body weight (WMD -1.14 kg [95% CI -1.69 to -0.60]; p = 0.001) and BMI (WMD -0.43 kg.m2 [95% CI -0.58 to -0.27]; p = 0.001), but did not significantly affect fat mass, lean body mass, visceral fat, insulin, HbA1c, lipid profiles or blood pressure.

Intermittent fasting is effective for weight loss and specific cardiometabolic health markers in individuals with prediabetes or T2D. Additionally, IF is associated with a reduction in body weight and BMI compared to CR, without effects on glycaemic markers, lipid profiles or blood pressure.

Despite reaching enormous achievements in therapeutic approaches worldwide, GBM still remains the most incurable malignancy among various cancers. It emphasizes the necessity of adjuvant therapies from the perspectives of both patients and healthcare providers. Therefore, most emerging studies have focused on various complementary and adjuvant therapies. Among them, metabolic therapy has received special attention, and metformin has been considered as a treatment in various types of cancer, including GBM. It is clearly evident that reaching efficient approaches without a comprehensive evaluation of the key mechanisms is not possible. Among the studied mechanisms, one of the more challenging ones is the effect of metformin on apoptosis and senescence. Moreover, metformin is well known as an insulin sensitizer. However, if insulin signaling is facilitated in the tumor microenvironment, it may result in tumor growth. Therefore, to partially resolve some paradoxical issues, we conducted a narrative review of related studies to address the following questions as comprehensively as possible: 1) Does the improvement of cellular insulin function resulting from metformin have detrimental or beneficial effects on GBM cells? 2) If these effects are detrimental to GBM cells, which is more important: apoptosis or senescence? 3) What determines the cellular decision between apoptosis and senescence?

Circadian oscillatory system plays a key role in coordinating the metabolism of most organisms. Perturbation of genetic effects and misalignment of circadian rhythms result in circadian dysfunction and signs of metabolic disorders. The eating-fasting cycle can act on the peripheral circadian clocks, bypassing the photoperiod. Therefore, time-restricted eating (TRE) can improve metabolic health by adjusting eating rhythms, a process achieved through reprogramming of circadian genomes and metabolic programs at different tissue levels or remodeling of the intestinal microbiota, with omics technology allowing visualization of the regulatory processes. Here, we review recent advances in circadian regulation of metabolism, focus on the potential application of TRE for rescuing circadian dysfunction and metabolic disorders with the contribution of intestinal microbiota in between, and summarize the significance of omics technology.

Maintaining metabolic balance relies on accumulating nutrients during feeding periods and their subsequent release during fasting. In obesity and metabolic disorders, strategies aimed at reducing food intake while simulating fasting have garnered significant attention for weight loss. Caloric restriction (CR) diets and intermittent fasting (IF) interventions have emerged as effective approaches to improving cardiometabolic health. Although the comparative metabolic benefits of CR versus IF remain inconclusive, this review focuses on various forms of IF, particularly time-restricted eating (TRE).

This study employs a narrative review methodology, systematically collecting, synthesizing, and interpreting the existing literature on TRE and its metabolic effects. A comprehensive and unbiased search of relevant databases was conducted to identify pertinent studies, including pre-clinical animal studies and clinical trials in humans. Keywords such as "Obesity," "Intermittent Fasting," "Time-restricted eating," "Chronotype," and "Circadian rhythms" guided the search. The selected studies were critically appraised based on predefined inclusion and exclusion criteria, allowing for a thorough exploration and synthesis of current knowledge.

This article synthesizes pre-clinical and clinical studies on TRE and its metabolic effects, providing a comprehensive overview of the current knowledge and identifying gaps for future research. It explores the metabolic outcomes of recent clinical trials employing different TRE protocols in individuals with overweight, obesity, or type II diabetes, emphasizing the significance of individual chronotype, which is often overlooked in practice. In contrast to human studies, animal models underscore the role of the circadian clock in mitigating metabolic disturbances induced by obesity through time-restricted feeding (TRF) interventions. Consequently, we examine pre-clinical evidence supporting the interplay between the circadian clock and TRF interventions. Additionally, we provide insights into the role of the microbiota, which TRE can modulate and its influence on circadian rhythms.

No trial to date has tested the effects of late time-restricted eating (lTRE) on glycemic control or body composition in adolescents with type 2 diabetes (T2D).

The objective of the current study was to examine the feasibility, acceptability, and preliminary efficacy of lTRE compared to a prolonged eating window in adolescents with T2D.

A 12-week, randomized, controlled, feasibility study of lTRE compared to control in adolescents with obesity and new onset T2D was conducted.

Eligible participants were 13-21 years old; with a diagnosis of T2D, on metformin monotherapy, recruited from Children's Hospital Los Angeles, between January 2021 and December of 2022. From 36 eligible participants, 27 were enrolled (75% recruitment rate; age: 16.5 ± 1.7 years, HbA1c: 6.6 ± 0.9%, 22/27 [81%] Hispanic, 17/27 [63%] female, 23/27 [85%] public insurance; all p-values >.05), and 23 of 27 completed the protocol.

Participants wore a continuous glucose monitor (CGM) daily and were randomized to one of two meal-timing schedules for 12-weeks: (1) lTRE (eating all food between 12:00 PM and 20:00 PM without calorie counting or recommended daily caloric intake) or (2) Control (eating over a period of 12 or more hours per day).

Study recruitment, retention and adherence to intervention arms were captured to operationalize feasibility. Glucose control (HbA1c), weight loss (%BMIp95), total body fat mass on DEXA, sleep, and dietary intake were explored as secondary outcomes.

Analyses were based on the intention to treat (ITT) population. Between-group differences in clinical outcomes were assessed using mixed-effects longitudinal regression models.

Overall adherence to the 8-hr lTRE was 6.2 ± 1.1 d/wk and Control was 5.9 ± 0.9 d/wk. Participants assigned to lTRE indicated that limiting their eating window did not negatively affect their daily functioning and no adverse events were reported. In this pilot study, lTRE led to a reduction in %BMIp95 (-3.4%-95%CI: -6.1, -0.7, p = 0.02), HbA1c (-0.4%, 95%CI: -0.9, -0.01, p = .06), and ALT (-31.1 U/L, 95%CI: -60, -2, p = .05) within the group. There was no significant difference observed between lTRE and control across these measures (all p > .05). The lTRE group had a -271.4 (95% CI, -565.2, 5.2) kcal/day energy reduction compared to a +293.2 (95% CI: 30.4, 552.7) kcal/day increase in Control (p = .01). There were no significant changes observed in sleep or eating behaviors over the study period between groups.

Recruitment and retention rates suggest a trial of lTRE in adolescents with T2D was feasible. lTRE was seen as acceptable by participants and adherence was high. A revised intervention, building on the successful elements of this pilot alongside adapting implementations strategies to augment adherence and engagement, should therefore be considered.

There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity.

We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity.

A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%; P = 0.61], headache [0%, 95%CI: -1% to 2%; P = 0.86] and dropout [1%, 95%CI: -2% to 4%; P = 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%; P = 0.08].

This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile.

Intermittent fasting (IF), a dietary pattern alternating between eating and fasting periods within a 24-hour cycle, has garnered recognition for its potential to enhance both healthspan and lifespan in animal models and humans. It also shows promise in alleviating age-related diseases, including neurodegeneration. Vascular cognitive impairment (VCI) spans a severity range from mild cognitive deficits to severe cognitive deficits and loss of function in vascular dementia. Chronic cerebral hypoperfusion has emerged as a significant contributor to VCI, instigating vascular pathologies such as microbleeds, blood-brain barrier dysfunction, neuronal loss, and white matter lesions. Preclinical studies in rodents strongly suggest that IF has the potential to attenuate pathological mechanisms, including excitotoxicity, oxidative stress, inflammation, and cell death pathways in VCI models. Hence, this supports evaluating IF in clinical trials for both existing and at-risk VCI patients. This review compiles existing data supporting IF's potential in treating VCI-related vascular and neuronal pathologies, emphasizing the mechanisms by which IF may mitigate these issues. Hence providing a comprehensive overview of the available data supporting IF's potential in treating VCI by emphasizing the underlying mechanisms that make IF a promising intervention for VCI.

Time-restricted eating (TRE), a popular form of intermittent fasting, has shown benefits for improving metabolic diseases and cardiometabolic health. However, the effect of TRE in the regulation of blood pressure in primary hypertension remains unclear.

A 6-week randomized controlled trial was conducted, in which a total of 74 stage 1 primary hypertensive patients without high-risk were randomly assigned to Dietary Approaches to Stop Hypertension (DASH) group (n = 37) or DASH + TRE group (n = 37). Participants in the DASH + TRE group were instructed to consume their food within an 8-h window. Scientific research platform in We Chat application was used to track participants. The primary outcome was blood pressure. The secondary outcomes included body composition, cardiometabolic risk factors, inflammation-related parameters, urinary Na+ excretion, other clinical variables and safety outcomes.

The reduction of systolic blood pressure and diastolic blood pressure were 5.595 ± 4.072 and 5.351 ± 5.643 mm Hg in the DASH group and 8.459 ± 4.260 and 9.459 ± 4.375 mm Hg in the DASH + TRE group. DASH + TRE group improved blood pressure diurnal rhythm. Subjects in DASH + TRE group had decreased extracellular water and increased urinary Na+ excretion. Furthermore, the decrease in blood pressure was associated with a reduction of extracellular water or increase in urinary Na+ excretion. In addition, safety outcomes such as nighttime hunger were also reported.

Our study demonstrated that 8-h TRE + DASH diet caused a greater decrease in blood pressure in stage 1 primary hypertensive patients than DASH diet. This study may provide novel insights into the benefits of lifestyle modification in the treatment of primary hypertension.

https://www.chictr.org.cn/ (ChiCTR2300069393, registered on March 15, 2023).

This qualitative study aimed to explore the experiences of participants who were enrolled in 6-month controlled weight loss interventions with 2-month follow-up to better understand the process of behaviour change and maintenance.

Fifteen participants who completed or dropped out from either a daily energy restriction or intermittent fasting group were recruited using maximum variation purposive sampling. In-depth, semi-structured interviews were conducted at the 2-month follow-up phase. All interviews were transcribed and analysed using thematic analysis, guided by behaviour change models including transtheoretical model, social cognitive theory and integrated model of change.

Participants following both diets showed similar behaviour change patterns. Their first motivations were mostly external and relied on 'accountability' to adhere to the diet when initiating the dietary changes. Participants highlighted the importance of frequent reviews and monitoring in assisting their adherence. This feedback system promoted the development of self-efficacy and internalised motivation to encourage an 'ownership'. Participants who transitioned successfully from relying on accountability to take 'ownership' of the intervention were more capable of tackling challenges and tailoring their diet to form a new routine for long-term maintenance.

External motivations were key to initiate while internalised motivations were more important to sustain the behaviour change. Health professionals can assist this process through routine monitoring and feedback processes in clinical practice.

Diabetes mellitus is a collection of metabolic disorders marked by elevated levels of glucose in the blood due to irregularities in the generation or functioning of insulin. Medical nutrition therapy and weight loss are crucial elements in the management of diabetes and the prevention of complications. Several diets have become popular over time for the goal of achieving weight loss, but their popularity has declined due to a lack of reliable scientific evidence. This study classifies popular diets into three categories: diets that manage the composition of macronutrients, diets that restrict specific foods or food groups, and diets that manipulate meal timing. The review includes research studies that investigated the effects of popular diets on the prevention, management, and complications of diabetes. It is clear that different popular diets can have positive effects on both preventing and treating diabetes and preventing and treating complications related to diabetes. However, it is not practical to determine which diet is the most effective option for preventing or controlling diabetes. Thus, the main focus should be on common underlying factors that support well-being, such as decreasing the intake of refined grains and added sugar, choosing non-starchy vegetables, and giving priority to whole foods over processed foods whenever possible, until there is stronger evidence supporting the specific benefits of different dietary patterns.

A growing body of evidence has supported the health benefits of extended daily fasting, known as time-restricted eating (TRE); however, whether the addition of TRE enhances the known benefits of calorie restriction (CR) remains unclear.

PubMed, Scopus, the Cochrane Library, and Google Scholar were searched through April 2023. This systematic review includes randomized controlled trials (RCTs) that compared CR + TRE with CR alone in energy-matched conditions of at least 8 weeks in duration that assessed changes in body weight and cardiometabolic disease risk factors in adults with overweight and/or obesity.

Seven studies were identified (n = 579). Two studies reported greater weight loss and reductions in diastolic blood pressure with CR + TRE compared with CR alone after 8 to 14 weeks, whereas one study reported greater improvements in triglycerides and glucose tolerance with CR + TRE (3 days/week) compared with CR alone following 26 weeks. One study reported significant increases in homeostatic model assessment of insulin resistance (HOMA-IR) levels with CR + TRE versus CR alone after 8 weeks. There were no statistically significant differences in any other outcome variable between the two interventions.

The addition of TRE to CR regimens resulted in greater weight loss and improvements in cardiometabolic risk factors in some studies; however, the majority of studies did not find additional benefits.

Ionizing radiation (IR)-induced damage to the hematopoietic system is a prominent symptom following exposure to total body irradiation (TBI). The exploration of strategies aimed at to mitigating radiation-induced hematopoietic damage assumes paramount importance. Time-restricted feeding (TRF) has garnered attention for its beneficial effects in various diseases. In this study, we evaluated the preventive effects of TRF on TBI-induced hematopoietic damage. The results suggested that TRF significantly enhanced the proportion and function of hematopoietic stem cells in mice exposed to 4 Gy TBI. These effects might be attributed to the inhibition of the NOX-4/ROS/p38 MAPK pathway in hematopoietic stem cells. TRF also influenced the expression of nuclear factor erythroid2-related factor 2 and increased glutathione peroxidase activity, thereby promoting the clearance of reactive oxygen species. Furthermore, TRF alleviated aberrations in plasma metabolism by inhibiting the mammalian target of rapamycin. These findings suggest that TRF may represent a novel approach to preventing hematopoietic radiation damage.

Time-restricted eating (TRE) has emerged as a dietary strategy that restricts food consumption to a specific time window and is commonly applied to facilitate weight loss. The benefits of TRE on adipose tissue have been evidenced in human trials and animal models; however, its impact on bone tissue remains unclear. To systematically synthesize and examine the evidence on the impact of TRE on bone health (bone mineral content (BMC), bone mineral density (BMD), and bone turnover factors), PubMed, Scopus, Cochrane CENTRAL, and Web of Science databases were systematically explored from inception to 1 October 2023 searching for randomized controlled trials (RCTs) aimed at determining the effects of TRE on bone health in adults (≥18 years). The Cochrane Handbook and the PRISMA recommendations were followed. A total of seven RCTs involving 313 participants (19 to 68 years) were included, with an average length of 10.5 weeks (range: 4 to 24 weeks). Despite the significant weight loss reported in five out of seven studies when compared to the control, our meta-analysis showed no significant difference in BMD (g/cm2) between groups (MD = -0.009, 95% CI: -0.026 to 0.009, p = 0.328; I2 = 0%). BMC and bone turnover markers between TRE interventions and control conditions were not meta-analyzed because of scarcity of studies (less than five). Despite its short-term benefits on cardiometabolic health, TRE did not show detrimental effects on bone health outcomes compared to those in the control group. Nevertheless, caution should be taken when interpreting our results due to the scarcity of RCTs adequately powered to assess changes in bone outcomes.

Circadian rhythms are evolutionarily programmed biological rhythms that are primarily entrained by the light cycle. Disruption of circadian rhythms is an important risk factor for several metabolic disorders. Photoperiod is defined as total duration of light exposure in a day. With the extended use of indoor/outdoor light, smartphones, television, computers, and social jetlag people are exposed to excessive artificial light at night increasing their photoperiod. Importantly long photoperiod is not limited to any geographical region, season, age, or socioeconomic group, it is pervasive. Long photoperiod is an established disrupter of the circadian rhythm and can induce a range of chronic health conditions including adiposity, altered hormonal signaling and metabolism, premature ageing, and poor psychological health. This review discusses the impact of exposure to long photoperiod on circadian rhythms, metabolic and mental health, hormonal signaling, and ageing and provides a perspective on possible preventive and therapeutic approaches for this pervasive challenge.

Patients with short bowel syndrome (SBS) dependent on home parenteral nutrition (HPN) commonly cycle infusions overnight, likely contributing to circadian misalignment and sleep disruption.

The objective of this quasi-experimental, single-arm, controlled, pilot trial was to examine the feasibility, safety, and efficacy of daytime infusions of HPN in adults with SBS without diabetes. Enrolled patients were fitted with a continuous glucose monitor and wrist actigraph and were instructed to cycle their infusions overnight for 1 wk, followed by daytime for another week. The 24-h average blood glucose, the time spent >140 mg/dL or <70 mg/dL, and sleep fragmentation were derived for each week and compared using Wilcoxon signed-rank test. Patient-reported quality-of-life outcomes were also compared between the weeks.

Twenty patients (mean age, 51.7 y; 75% female; mean body mass index, 21.5 kg/m2) completed the trial. Overnight infusions started at 21:00 and daytime infusions at 09:00. No serious adverse events were noted. There were no differences in 24-h glycemia (daytime-median: 93.00 mg/dL; 95% CI: 87.7-99.9 mg/dL, compared with overnight-median: 91.1 mg/dL; 95% CI: 89.6-99.0 mg/dL; P = 0.922). During the day hours (09:00-21:00), the mean glucose concentrations were 13.5 (5.7-22.0) mg/dL higher, and the time spent <70 mg/dL was 15.0 (-170.0, 22.5) min lower with daytime than with overnight HPN. Conversely, during the night hours (21:00-09:00), the glucose concentrations were 16.6 (-23.1, -2.2) mg/dL lower with daytime than with overnight HPN. There were no differences in actigraphy-derived measures of sleep and activity rhythms; however, sleep timing was later, and light at night exposure was lower with daytime than with overnight HPN. Patients reported less sleep disruptions due to urination and fewer episodes of uncontrollable diarrhea or ostomy output with daytime HPN.

Daytime HPN was feasible and safe in adults with SBS and, compared with overnight HPN, improved subjective sleep without increasing 24-h glucose concentrations. This trial was registered at clinicaltrials.gov as NCT04743960 (https://classic.

gov/ct2/show/NCT04743960).

Early time-restricted carbohydrate consumption (eTRC) is a novel dietary strategy that involves restricting carbohydrate-rich food intake to the morning and early afternoon to align with circadian variations in glucose tolerance. We examined the efficacy, feasibility and safety of eTRC in individuals with type 2 diabetes under free-living conditions.

In this randomised, parallel-arm, open label, controlled trial, participants with type 2 diabetes and overweight/obesity (age 67.2±7.9 years, 47.8% women, BMI 29.4±3.7 kg/m2, HbA1c 49±5 mmol/mol [6.6±0.5%]) were randomised, using computer-generated random numbers, to a 12 week eTRC diet or a Mediterranean-style control diet with matched energy restriction and macronutrient distribution (50% carbohydrate, 30% fat and 20% protein). The primary outcome was the between-group difference in HbA1c at 12 weeks. Body composition, 14 day flash glucose monitoring and food diary analysis were performed every 4 weeks. Mixed meal tolerance tests with mathematical beta cell function modelling were performed at baseline and after 12 weeks.

Twelve (85.7%) participants in the eTRC arm and 11 (84.6%) participants in the control arm completed the study, achieving similar reductions in body weight and fat mass. The two groups experienced comparable improvements in HbA1c (-3 [-6, -0.3] mmol/mol vs -4 [-6, -2] mmol/mol, corresponding to -0.2 [-0.5, 0]% and -0.3 [-0.5, -0.1]%, respectively, p=0.386), fasting plasma glucose, flash glucose monitoring-derived glucose variability and mixed meal tolerance test-derived glucose tolerance, insulin resistance, insulin clearance and plasma glucagon levels, without changes in model-derived beta cell function parameters, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and non-esterified fatty acid levels. The two diets similarly reduced liver function markers and triglyceride levels, being neutral on other cardiometabolic and safety variables. In exploratory analyses, diet-induced changes in body weight and glucometabolic variables were not related to the timing of carbohydrate intake.

The proposed eTRC diet provides a feasible and effective alternative option for glucose and body weight management in individuals with type 2 diabetes, with no additional metabolic benefits compared with conventional dieting.

ClinicalTrials.gov NCT05713058 FUNDING: This study was supported by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the Italian Society of Diabetology (SID).