דו״ח מאומת

<h4>Purpose of the review</h4>Diabesity, the coexistence of type 2 diabetes mellitus (T2DM) and obesity, represents one of the major global health challenges. This review aims to synthesize current evidence on personalized medical nutrition therapy (MNT) and structured physical exercise as cornerstones of diabesity management, with a particular focus on very-low-energy ketogenic therapy (VLEKT).<h4>Recent findings</h4>Conventional pharmacotherapies improve glycemic control and promote weight reduction but often fail to fully address the multifactorial pathophysiology of diabesity. MNT has demonstrated significant efficacy in improving glycemic regulation, reducing weight, and modulating cardiometabolic risk factors. Among dietary strategies, the Mediterranean diet provides sustainable benefits, while more intensive interventions such as low-energy diets and ketogenic diets can induce rapid and clinically meaningful improvements, with emerging evidence supporting favorable effects on gut microbiota and inflammation. Complementary lifestyle interventions, particularly structured exercise programs combining aerobic and resistance training, further enhance metabolic outcomes and may contribute to T2DM remission in selected patients. Integration of MNT with incretin-based therapies holds promise for optimizing efficacy while preserving nutritional adequacy and functional health. Effective management of diabesity requires a multidisciplinary, precision-based approach. Personalized MNT and structured exercise represent foundational strategies, while pharmacological therapies provide valuable adjuncts. Among available options, VLEKT stands out for its ability to target key mechanisms of diabesity, including insulin resistance, adiposity, and chronic inflammation. Future diabesity care will rely on integrating nutrition, physical exercise, and pharmacotherapy within individualized frameworks to achieve sustained metabolic control and improved quality of life.…

PMID: 41813871

Shift work and jet lag, characterized by circadian misalignment, can disrupt several physiological activities, but whether they affect the rhythm of glucose uptake and insulin sensitivity remain unclear. In the present study, female C57BL/6J mice were maintained for four weeks under the condition of 8-hour phase advance and delay every 3-4 days to mimic shift work. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were performed repeatedly at Zeitgeber time (ZT) 0, ZT6, ZT12, and ZT18. Glucose-stimulated insulin secretion (GSIS) test was performed at ZT6. We found that the average level of daily glucose tolerance did not decrease but the phase of glucose tolerance advanced by 2.27 hours and the amplitude attenuated by 20.4% in shift work mice. At ZT6, IPITT showed blood glucose at 30 min after insulin injection decreased faster in shift work mice (-3.50±0.74mmol/L, -61.58±7.89%) than that in control mice (-2.11±1.10mmol/L, -33.72±17.24%), but IPGTT and GSIS test showed no significant difference between the two groups. Food intake monitor showed that the feeding time of shift work mice continued to advance. Restricting feed to a fixed 12-hour period alleviated the increase of insulin sensitivity induced by shift-work. We also observed that an increase of blood glucose and liver glycogen at ZT0, as well as a phase advance of liver clock genes and some glucose metabolism-related genes such as forkhead box O1 (Foxo1) and peroxisome proliferator activated receptor alpha (Pparα) in shift work mice. Our results showed that light change-simulated shift work altered insulin sensitivity during the light phase and shifted glucose tolerance rhythms in female mice, suggesting a causal association between long-term shift work and type 2 diabetes.…

PMID: 31851682

Type 2 diabetes (T2D) is a chronic condition that occurs in insulin-resistant people with reduced glucose uptake. It is contributed to and exacerbated by a poor diet that results in accumulation of adipose tissue, high blood sugar, and other metabolic issues. Because humans have undergone food scarcity throughout history, our species has adapted a fat reserve genotype. This adaptation is no longer beneficial, as eating at a higher frequency than that of our ancestors has had a significant effect on T2D development. Eating at high frequencies disrupts the circadian clock, the circadian rhythm, and the composition of the gut microbiome, as well as hormone secretion and sensitivity. The current literature suggests an improved diet requires meal consistency, avoiding late-night eating, low meal frequency, and fasting to increase metabolic health. In addition, fasting as a treatment for T2D must be used correctly for beneficial results. Early time-restricted eating (TRE) provides many benefits such as improving insulin resistance, cognitive function, and glycemic control. Alternate-day fasting (ADF), 5:2 fasting, and long-term fasting all have benefits; however, they may be less advantageous than early TRE. Therefore, eating pattern adjustments can be used to reduce T2D if used correctly.…

PMID: 37049602

Due to the Earth's rotation, the natural environment exhibits a light-dark diurnal cycle close to 24 hours. To adapt to this energy intake pattern, organisms have developed a 24-hour rhythmic diurnal cycle over long periods, known as the circadian rhythm, or biological clock. With the gradual advancement of research on the biological clock, it has become increasingly evident that disruptions in the circadian rhythm are closely associated with the occurrence of type 2 diabetes (T2D). To further understand the progress of research on T2D and the biological clock, this paper reviews the correlation between the biological clock and glucose metabolism and analyzes its potential mechanisms. Based on this, we discuss the potential factors contributing to circadian rhythm disruption and their impact on the risk of developing T2D, aiming to explore new possible intervention measures for the prevention and treatment of T2D in the future. Under the light-dark circadian rhythm, in order to adapt to this change, the human body forms an internal biological clock involving a variety of genes, proteins and other molecules. The main mechanism is the transcription-translation feedback loop centered on the CLOCK/BMAL1 heterodimer. The expression of important circadian clock genes that constitute this loop can regulate T2DM-related blood glucose traits such as glucose uptake, fat metabolism, insulin secretion/glucagon secretion and sensitivity in various peripheral tissues and organs. In addition, sleep, light, and dietary factors under circadian rhythms also affect the occurrence of T2DM.…

PMID: 38872971

Circadian rhythms are 24-h cycles regulated by endogeneous molecular oscillators called the circadian clock. The effects of diet on circadian rhythmicity clearly involves a relationship between factors such as meal timings and nutrients, known as chrononutrition. Chrononutrition is influenced by an individual's "chronotype", whereby "evening chronotypes" or also termed "later chronotype" who are biologically driven to consume foods later in the day. Research in this area has suggested that time of day is indicative of having an influence on the postprandial glucose response to a meal, therefore having a major effect on type 2 diabetes. Cross-sectional and experimental studies have shown the benefits of consuming meals early in the day than in the evening on postprandial glycaemia. Modifying the macronutrient composition of night meals, by increasing protein and fat content, has shown to be a simple strategy to improve postprandial glycaemia. Low glycaemic index (GI) foods eaten in the morning improves glycaemic response to a greater effect than when consumed at night. Timing of fat and protein (including amino acids) co-ingested with carbohydrate foods, such as bread and rice, can reduce glycaemic response. The order of food presentation also has considerable potential in reducing postprandial blood glucose (consuming vegetables first, followed by meat and then lastly rice). These practical recommendations could be considered as strategies to improve glycaemic control, rather than focusing on the nutritional value of a meal alone, to optimize dietary patterns of diabetics. It is necessary to further elucidate this fascinating area of research to understand the circadian system and its implications on nutrition that may ultimately reduce the burden of type 2 diabetes.…

PMID: 32075959

This systematic review aimed to summarize randomized clinical trials that compared the postprandial glycemic and insulinemic metabolic response after eating isocaloric and standardized carbohydrate meals consumed at two moments: morning versus night, in healthy individuals who were not shift workers. The search strategy consisted of an electronic search using the following electronic databases: MEDLINE (via PubMed), EMBASE (via Elsevier), LILACs (Virtual Health Library - VHL), Cochrane Registers of Clinical Trials (CENTRAL, via Wiley) and gray literature (Opengray.eu). The PICO strategy was used to define the search terms (P: healthy adults, I: nocturnal intake, C: morning intake, O: area under the curve (AUC) of the postprandial glucose and insulin response). This review was reported according to the PRISMA statement. From the 3757 articles found, 412 were duplicates and excluded, totaling 3345 that had their titles and abstracts read. A total of 42 articles met the inclusion criteria and were read in full, and eight studies were included in the systematic review. The certainty of the evidence was assessed using GRADE. The results showed, with moderate quality of evidence, a postprandial response with higher glycemic values in the evening compared to the morning (SMD = 1.30; 95% CI, 1.01 to 1.59; I…

PMID: 35512764

Gestational diabetes mellitus (GDM) is a heterogeneous disorder that compromises maternal and offspring health. Conventional medical nutrition therapy focuses on nutrient composition and caloric targets but largely omits timing and individualized biology. This narrative review synthesizes mechanistic, epidemiologic and interventional evidence linking circadian biology and meal timing (chrononutrition) to maternal glycemic control. Observational cohorts associate late eating and breakfast skipping with worse glycemia, while pilot interventions and CGM-based studies indicate that front-loading carbohydrates, restricting evening carbohydrate, extending overnight fasting (≈10-12 h), and simple within-meal sequencing can reduce postprandial excursions and increase time-in-range. We propose a pragmatic, tiered clinical pathway in which routine second-trimester triage (50 g glucose challenge test and ultrasound abdominal subcutaneous fat thickness) identifies higher-risk women for short-term CGM phenotyping and prioritized chrononutrition counseling. Integrating phenotype-matched timing interventions with dietetic support and digital decision tools allows rapid, individualized adjustments informed by real-time glucose patterns and patient chronotype. In principle, this tiered strategy could improve daily glycemic profiles, reduce the need for pharmacotherapy, and translate into better neonatal outcomes if supported by larger randomized trials. Chrononutrition therefore offers a promising extension of standard care: simple, low-cost adjustments to "when" food is eaten, supported by digital tools, could allow nutrition therapy for GDM to become more precise, more responsive, and ultimately more effective for both mother and child. Key priorities include validating bedside and chrono-omic stratifiers, testing scalable delivery platforms, and ensuring equitable access to personalized chrononutrition in pregnancy.…

PMID: 41295235

The International Society of Sports Nutrition (ISSN) provides an objective and critical review regarding the timing of macronutrients in reference to healthy, exercising adults and in particular highly trained individuals on exercise performance and body composition. The following points summarize the position of the ISSN:Nutrient timing incorporates the use of methodical planning and eating of whole foods, fortified foods and dietary supplements. The timing of energy intake and the ratio of certain ingested macronutrients may enhance recovery and tissue repair, augment muscle protein synthesis (MPS), and improve mood states following high-volume or intense exercise.Endogenous glycogen stores are maximized by following a high-carbohydrate diet (8-12 g of carbohydrate/kg/day [g/kg/day]); moreover, these stores are depleted most by high volume exercise.If rapid restoration of glycogen is required (< 4 h of recovery time) then the following strategies should be considered:aggressive carbohydrate refeeding (1.2 g/kg/h) with a preference towards carbohydrate sources that have a high (> 70) glycemic indexthe addition of caffeine (3-8 mg/kg)combining carbohydrates (0.8 g/kg/h) with protein (0.2-0.4 g/kg/h) Extended (> 60 min) bouts of high intensity (> 70% VO…

PMID: 28919842

Time-qualified dietary interventions, including time-restricted eating (TRE), intermittent fasting (IF), and periodic fasting-mimicking diets (FMDs), have emerged as strategies to improve metabolic health. While preclinical studies consistently demonstrate robust effects on energy metabolism, cardiometabolic function, and longevity, translation to humans remains heterogeneous. In free-living settings, most metabolic improvements observed with TRE and IF appear primarily driven by spontaneous caloric restriction rather than meal timing per se, and isocaloric randomized controlled trials generally show no additional benefits compared to standard calorie restriction. Evidence supporting circadian-specific advantages, particularly for early TRE, is promising but inconsistent and often context-dependent. Important uncertainties also persist regarding long-term efficacy, lean mass preservation, safety in specific populations, and the physiological impact of extended fasting windows. Despite these controversies, time-qualified diets represent a paradigm shift in nutritional science by integrating chronobiology with dietary patterns. Future directions include tailoring eating windows to individual chronotypes, combining fasting regimens with high-quality dietary patterns and structured physical activity, and clarifying the molecular mechanisms that may mediate calorie-independent benefits. Large, long-term, mechanistically informed human trials are essential to determine whether aligning eating behaviors with circadian biology can produce durable clinical improvements. Such work will ultimately shape the role of personalized chrononutrition in preventive and therapeutic nutrition.…

PMID: 41470839

Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity. The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis. Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload. Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.…

PMID: 39192263

<h4>Purpose of the review</h4>Diabesity, the coexistence of type 2 diabetes mellitus (T2DM) and obesity, represents one of the major global health challenges. This review aims to synthesize current evidence on personalized medical nutrition therapy (MNT) and structured physical exercise as cornerstones of diabesity management, with a particular focus on very-low-energy ketogenic therapy (VLEKT).<h4>Recent findings</h4>Conventional pharmacotherapies improve glycemic control and promote weight reduction but often fail to fully address the multifactorial pathophysiology of diabesity. MNT has demonstrated significant efficacy in improving glycemic regulation, reducing weight, and modulating cardiometabolic risk factors. Among dietary strategies, the Mediterranean diet provides sustainable benefits, while more intensive interventions such as low-energy diets and ketogenic diets can induce rapid and clinically meaningful improvements, with emerging evidence supporting favorable effects on gut microbiota and inflammation. Complementary lifestyle interventions, particularly structured exercise programs combining aerobic and resistance training, further enhance metabolic outcomes and may contribute to T2DM remission in selected patients. Integration of MNT with incretin-based therapies holds promise for optimizing efficacy while preserving nutritional adequacy and functional health. Effective management of diabesity requires a multidisciplinary, precision-based approach. Personalized MNT and structured exercise represent foundational strategies, while pharmacological therapies provide valuable adjuncts. Among available options, VLEKT stands out for its ability to target key mechanisms of diabesity, including insulin resistance, adiposity, and chronic inflammation. Future diabesity care will rely on integrating nutrition, physical exercise, and pharmacotherapy within individualized frameworks to achieve sustained metabolic control and improved quality of life.…

PMID: 41813871

Gestational diabetes mellitus (GDM) is a heterogeneous disorder that compromises maternal and offspring health. Conventional medical nutrition therapy focuses on nutrient composition and caloric targets but largely omits timing and individualized biology. This narrative review synthesizes mechanistic, epidemiologic and interventional evidence linking circadian biology and meal timing (chrononutrition) to maternal glycemic control. Observational cohorts associate late eating and breakfast skipping with worse glycemia, while pilot interventions and CGM-based studies indicate that front-loading carbohydrates, restricting evening carbohydrate, extending overnight fasting (≈10-12 h), and simple within-meal sequencing can reduce postprandial excursions and increase time-in-range. We propose a pragmatic, tiered clinical pathway in which routine second-trimester triage (50 g glucose challenge test and ultrasound abdominal subcutaneous fat thickness) identifies higher-risk women for short-term CGM phenotyping and prioritized chrononutrition counseling. Integrating phenotype-matched timing interventions with dietetic support and digital decision tools allows rapid, individualized adjustments informed by real-time glucose patterns and patient chronotype. In principle, this tiered strategy could improve daily glycemic profiles, reduce the need for pharmacotherapy, and translate into better neonatal outcomes if supported by larger randomized trials. Chrononutrition therefore offers a promising extension of standard care: simple, low-cost adjustments to "when" food is eaten, supported by digital tools, could allow nutrition therapy for GDM to become more precise, more responsive, and ultimately more effective for both mother and child. Key priorities include validating bedside and chrono-omic stratifiers, testing scalable delivery platforms, and ensuring equitable access to personalized chrononutrition in pregnancy.…

PMID: 41295235