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Chrononutrition is a rapidly evolving field of nutritional epidemiology that addresses the complex relationship between temporal eating patterns, circadian rhythms, and metabolic health, but most prior research has focused on the cardiometabolic consequences of time-restricted feeding and intermittent fasting. The purpose of this topical review is to summarize epidemiological evidence from observational and intervention studies regarding the role of chrononutrition metrics related to eating timing and regularity in cardiometabolic health preservation and cardiovascular disease prevention. Observational studies are limited due to the lack of time-stamped diet data in most population-based studies. Findings from cohort studies generally indicate that breakfast skipping or the later timing of the first eating occasion, a later lunch and dinner, and a greater proportion of caloric intake consumed in the evening are associated with adverse cardiometabolic outcomes, including higher risk for coronary heart disease, hypertension, type 2 diabetes, obesity, dyslipidemia, and systemic inflammation. Randomized controlled trials are also limited, as most in the field of chrononutrition focus on the cardiometabolic consequences of time-restricted feeding. Overall, interventions that shift eating timing patterns to earlier in the day and that restrict evening caloric intake tend to have protective effects on cardiometabolic health, but small sample sizes and short follow-up are notable limitations. Innovation in dietary assessment approaches, to develop low-cost validated tools with acceptable participant burden that reliably capture chrononutrition metrics, is needed for advancing observational evidence. Culturally responsive pragmatic intervention studies with sufficiently large and representative samples are needed to understand the impact of fixed and earlier eating timing schedules on cardiometabolic health. Additional research is warranted to understand the modifiable determinants of temporal eating patterns, to investigate the role of chrononutrition in the context of other dimensions of diet (quantity, quality, and food and nutrition security) in achieving cardiometabolic health equity, and to elucidate underlying physiological mechanisms.

The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P (n = 21) versus a heart-healthy, calorie-restricted (CR, n = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p

The hepatocytes within the liver present an immense capacity to adapt to changes in nutrient availability. Here, by using high resolution volume electron microscopy, we map how hepatic subcellular spatial organization is regulated during nutritional fluctuations and as a function of liver zonation. We identify that fasting leads to remodeling of endoplasmic reticulum (ER) architecture in hepatocytes, characterized by the induction of single rough ER sheet around the mitochondria, which becomes larger and flatter. These alterations are enriched in periportal and mid-lobular hepatocytes but not in pericentral hepatocytes. Gain- and loss-of-function in vivo models demonstrate that the Ribosome receptor binding protein1 (RRBP1) is required to enable fasting-induced ER sheet-mitochondria interactions and to regulate hepatic fatty acid oxidation. Endogenous RRBP1 is enriched around periportal and mid-lobular regions of the liver. In obesity, ER-mitochondria interactions are distinct and fasting fails to induce rough ER sheet-mitochondrion interactions. These findings illustrate the importance of a regulated molecular architecture for hepatocyte metabolic flexibility.

Adipose tissue is the site of long-term energy storage. During the fasting state, exercise, and cold exposure, the white adipose tissue mobilizes energy for peripheral tissues through lipolysis. The mobilization of lipids from white adipose tissue to the liver can lead to excess triglyceride accumulation and fatty liver disease. Although the white adipose tissue is known to release free fatty acids, a comprehensive analysis of lipids mobilized from white adipocytes in vivo has not been completed. In these studies, we provide a comprehensive quantitative analysis of the adipocyte-secreted lipidome and show that there is interorgan crosstalk with liver. Our analysis identifies multiple lipid classes released by adipocytes in response to activation of lipolysis. Time-dependent analysis of the serum lipidome showed that free fatty acids increase within 30 min of β3-adrenergic receptor activation and subsequently decrease, followed by a rise in serum triglycerides, liver triglycerides, and several ceramide species. The triglyceride composition of liver is enriched for linoleic acid despite higher concentrations of palmitate in the blood. To further validate that these findings were a specific consequence of lipolysis, we generated mice with conditional deletion of adipose tissue triglyceride lipase exclusively in adipocytes. This loss of in vivo adipocyte lipolysis prevented the rise in serum free fatty acids and hepatic triglycerides. Furthermore, conditioned media from adipocytes promotes lipid remodeling in hepatocytes with concomitant changes in genes/pathways mediating lipid utilization. Together, these data highlight critical role of adipocyte lipolysis in interorgan crosstalk between adipocytes and liver.

Intermittent fasting (IF) and caloric restriction (CR) are dietary strategies to prevent and attenuate obesity associated with conditions and aging-related outcomes. This scoping review examined the cardiometabolic, cancer, and neurocognitive outcome differences between IF and CR interventions among adults. We applied a systematic approach to scope published randomized controlled trials (databases: PubMed, CINAHL Plus, PsychInfo, Scopus, and Google Scholar) from inception through August 2023. The initial search provided 389 unique articles which were critically appraised. Thirty articles met the eligibility criteria for inclusion: 12 were IF, 10 were CR, and 8 were combined IF and CR interventions. IF and CR were associated with weight loss; however, IF studies tended to report greater adherence compared with CR. Overall, IF and CR were equivalently effective across cardiometabolic, cancer, and neurocognitive outcomes. Our findings suggest that IF has health benefits in a variety of conditions and may be better accepted and tolerated than CR, but more comparative research is required.

We conducted this study to evaluate the efficacy of Curcumin and vitamin E on hot flashes, lipid profile, blood glucose, and hepatic & renal biomarkers. Eighty-four postmenopausal women were randomly assigned into three groups to receive one Curcumin 500 milligram, vitamin E 200 IU, or placebo capsules twice/daily/eight weeks. In comparison with placebo, vitamin E significantly decreased the number of hot flashes (P = 0.002), serum triglyceride (P < 0.001), and aspartate aminotransferase (P = 0.007), while it increased high-density lipoprotein cholesterol (P = 0.005). Curcumin decreased significantly fasting blood glucose (P = 0.007), total cholesterol (P = 0.015), and triglyceride (P = 0.007) compared to placebo. We conclude that vitamin E reduced the incidence of hot flashes by nearly one-third of the base amount. It improved serum lipid profile and aspartate aminotransferase. Curcumin ameliorated fasting blood glucose and serum lipid profile. [ABSTRACT FROM AUTHOR]

The article discusses the author's qualitative field research on contraceptive knowledge, attitudes, and practices among Algerian women. The research aims to address the challenges of conducting fieldwork on women's health topics in Algeria, where social norms and the medical model influence reproductive health decisions. The study reveals insights into women's experiences with contraception, highlighting the importance of understanding socio-cultural factors in addressing unmet contraceptive needs in Algeria. The author's research approach involves in-depth interviews, key informant interviews, and an online survey to explore women's lived experiences and contribute to existing evidence on contraceptive practices in Algeria. [Extracted from the article]

Purpose: We investigated the effects of a 16-wk combined exercise training on body composition, and metabolic and inflammatory markers in sedentary middle-aged workers. We also assessed whether alterations in metabolic markers were associated with changes in health-related outcomes. Methods: This randomized controlled trial involved 46 participants randomly allocated into control and exercise groups. The exercise group performed 16-wk combined aerobic and resistance training for 75 min per session, 3 times a week. Fasting blood samples were collected at baseline and after 16-wk intervention to determine lipid profile, and metabolic and inflammatory markers as primary outcomes. Results: A total of 36 participants completed the intervention (53.70 ± 6.92 yr old; n = 18 in each group). Waist circumference (interaction effect: F = 7.423, P = 0.002), fat mass (interaction effect: F = 5.070, P = 0.011), and muscle mass (interaction effect: F = 5.420, P = 0.007) were improved in the exercise group compared with the control group. Fasting glucose increased after the 16-wk follow-up (time effect: F = 73.253, P < 0.001), without an intergroup difference. Insulin levels were greater in the control compared with exercise group (group effect: F = 6.509, P = 0.015). The control group tended to increase the homeostatic model assessment of insulin resistance index (interaction effect: F = 3.493, P = 0.070) and to decrease the QUICKI index (interaction effect: F = 3.364, P = 0.075) to a greater extent compared with the exercise group. Exercise group reduced leptin (interaction effect: F = 11.175, P = 0.002) and adiponectin (interaction effect: F = 4.437, P = 0.043) concentrations in a greater magnitude than the control group. Interleukin (IL)-6 (time effect: F = 17.767, P < 0.001) and tumor necrosis factor α (time effect: F = 9.781, P = 0.004) concentrations decreased after the intervention, without an intergroup difference. IL-17A levels increased in the control compared with exercise group (interaction effect: F = 5.010, P = 0.033). Effects on adiponectin, IL-6, and IL-17A levels seem to depend on baseline body mass index, age, and sex. Percentage changes in leptin correlated positively with changes in homeostatic model assessment of insulin resistance index in the exercise (r = 0.565, P = 0.015) and control (r = 0.670, P = 0.002) groups. Conclusions: A combined training program can be an effective strategy to improve body composition and inflammatory markers and prevent marked reductions in insulin sensitivity among middle-aged workers. [ABSTRACT FROM AUTHOR]

• Ramadan Intermittent fasting (RIF) exerts beneficial metabolic effects and improves gastrointestinal motility. • A comparison between RIF and the traditional 16-hours intermittent fasting (16IF), a strategy for weight loss, is lacking. • By performing an observational clinical study we show that both 16IF and RIF are able, during 1-month, to reduce body weight. • RIF but not 16IF has beneficial effects on decrease of subcutaneous fat and liver steatosis. • Further studies need to investigate the effects of different models of IF in weight-cycling and long-term management of obesity and related dysmetabolic conditions. Ramadan Intermittent fasting (RIF) exerts beneficial metabolic effects and improves gastrointestinal motility. However, a comparison between RIF and the traditional 16-hours intermittent fasting (16IF), a strategy for weight loss, is lacking. A total of 34 subjects (median age 32.5 years, range 18–63 years; median BMI 24.5 Kg m-1², range 18.6–37.6 Kg m-1²) were assigned to RIF (N = 18) or 16IF (N = 16) for 30 days. We measured variations in anthropometric measures (BMI, waist, and abdominal circumference), serum insulin, glucose, cortisol, non-esterified fatty acid (NEFA), body fat composition (bioelectrical impedance analysis), and the ultrasonographic measurements of liver steatosis (Hepatorenal index, HRI) and thickness of subcutaneous (SAT) and visceral (VAT) fats. At baseline, BMI, rates of liver steatosis and distribution of normal weight, overweight, and obese subjects were comparable between the two groups. Body weight significantly decreased at the end of fasting in both RIF (-4.2 % vs baseline, P = 0.002) and 16IF (-2.1 % vs baseline, P = 0.002). Waist and abdominal circumferences significantly decreased only in RIF as well as the amount of body fat. In subjects with liver steatosis, SAT and VAT significantly decreased following RIF, but not 16h-IF, as well as the ultrasonographic HRI. Both 16IF and RIF are able, during 1-month, to reduce body weight. However, RIF but not 16IF also generates marked beneficial effects in terms of reduced subcutaneous fat and liver steatosis. Further studies urge to verify the effects of different models of IF in weight-cycling and long-term management of obesity and related dysmetabolic conditions, such as ectopic fat over-storage. [ABSTRACT FROM AUTHOR]

Ever since their introduction a decade ago, stable introns, a type of noncoding (nc)RNAs, are found to be key players in different important cellular processes acting through regulation of gene expression and feedback loops to maintain cellular homeostasis. Despite being commonly regarded as useless byproducts, recent studies in yeast suggested that stable introns are essential for cell survivability under starvation. In Drosophila, we found that a stable intron, sisR‐1, has a direct effect in regulating mitochondrial dynamics during short‐term fasting and subsequently improved overall oocyte quality. We speculated that the beneficial effects implicated by sisR‐1 is through the activation of mitohormesis, an interesting phenomenon in mitochondrial biology. Mitohormesis is suggested to improve health span and lifespan of cells and organisms, but the involvement of ncRNAs is not well‐documented. Here, we discuss the potential role of sisR‐1 and other ncRNAs in activating mitohormesis and the possible applications in improving cellular and organismal health. [ABSTRACT FROM AUTHOR]

Background and Aims: During fasting, bodily homeostasis is maintained due to hepatic production of glucose (gluconeogenesis) and ketone bodies (ketogenesis). The main hormones governing hepatic fuel production are glucagon and glucocorticoids that initiate transcriptional programs aimed at supporting gluconeogenesis and ketogenesis. Methods: Using primary mouse hepatocytes as an ex vivo model, we employed transcriptomic analysis (RNA‐seq), genome‐wide profiling of enhancer dynamics (ChIP‐seq), perturbation experiments (inhibitors, shRNA), hepatic glucose production measurements and computational analyses. Results: We found that in addition to the known metabolic genes transcriptionally induced by glucagon and glucocorticoids, these hormones induce a set of genes encoding transcription factors (TFs) thereby initiating transcriptional cascades. Upon activation by glucocorticoids, the glucocorticoid receptor (GR) induced the genes encoding two TFs: CCAAT/enhancer‐binding protein beta (C/EBPβ) and peroxisome proliferator‐activated receptor alpha (PPARα). We found that the GR‐C/EBPβ cascade mainly serves as a secondary amplifier of primary hormone‐induced gene programs. C/EBPβ augmented gluconeogenic gene expression and hepatic glucose production. Conversely, the GR‐PPARα cascade initiated a secondary transcriptional wave of genes supporting ketogenesis. The cascade led to synergistic induction of ketogenic genes which is dependent on protein synthesis. Genome‐wide analysis of enhancer dynamics revealed numerous enhancers activated by the GR‐PPARα cascade. These enhancers were proximal to ketogenic genes, enriched for the PPARα response element and showed increased PPARα binding. Conclusion: This study reveals abundant transcriptional cascades occurring during fasting. These cascades serve two separated purposes: the amplification of the gluconeogenic transcriptional program and the induction of a gene program aimed at enhancing ketogenesis. [ABSTRACT FROM AUTHOR]

Objective: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100–125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first‐trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first‐ trimester fasting plasma glucose levels, as compared with gestational diabetes, a well‐established risk factor for diabetes, in up to 5‐year follow‐up postpartum. Methods: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post‐delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic‐area under the curve (ROC‐AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status. Results: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut‐off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity. Conclusions: Increased first‐trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first‐trimester fasting plasma glucose has a more pronounced impact on progression to diabetes. Synopsis: First‐trimester fasting plasma glucose levels exceeding 86.5 mg/dL carry at least a comparable risk for type 2 diabetes progression as gestational diabetes, regardless of obesity status. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of small bowel motility disorders is performed by manometric evaluation of the contractile patterns of the small intestine. Conventional intestinal manometry systems include few pressure sensors at relatively long intervals. We have recently shown that high‐resolution jejunal manometry, with multiple closely spaced recording sites, allows the analysis of propagation patterns of intestinal motility in healthy subjects that cannot be detected with conventional manometry. The objective of this pilot study was to explore the feasibility and diagnostic value of high‐resolution intestinal manometry in patients with suspected small bowel dysmotility. Methods: Prospective pilot study evaluating intestinal motility patterns in 16 consecutive patients (16–61 years; 11 women) with severe, chronic digestive symptoms referred for the evaluation of intestinal motility and in 18 healthy controls (21–38 years; 8 women). A 36‐channel high‐resolution manometry catheter was orally placed under radiological guidance in the jejunum. Intestinal motility was continuously recorded for 3 h fasting and 2 h after a 450 kcal meal. The manometric recordings were analyzed in two formats: (a) with the high‐resolution data from 34 channels and (b) showing only the recordings from 5 channels separated by 7 cm intervals, mimicking a conventional manometry recording. Key Results: In the analysis mimicking conventional manometry, abnormal motility criteria were detected in six patients and in no healthy subject [bursts (n = 3), postprandial minute rhythm (n = 1) and myopathic pattern (n = 2)]. These classical dysmotility criteria were also detected by high‐resolution manometry. High‐resolution analysis detected one or more abnormal findings in seven additional patients that were not observed in any healthy subject, specifically: (a) abnormal propagation of Phase III (n = 3); (b) reduced propagated activity during Fasting Phase II (n = 4); (c) increased propagated activity during Fasting Phase II and postprandial phase (n = 1). Conclusions and Inferences: This pilot study suggests that high‐resolution intestinal manometry may improve the sensitivity of conventional manometry in the detection of intestinal motor dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this work was to assess the safety and effectiveness of concomitant iGlarLixi and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) use in adults with type 2 diabetes (T2D) who fasted during Ramadan. Methods: Of the 420 eligible participants from the SoliRam study, 174 were using SGLT-2i in addition to iGlarLixi and 246 were not using SGLT-2i, referred to as SGLT-2i user and non-user, respectively. The primary endpoint was the proportion of participants experiencing ≥ 1 severe and/or symptomatic documented (< 70 mg/dl [< 3.9 mmol/l]) hypoglycemia. Results: More than 50% of participants in both groups were male. The mean weight, glycated hemoglobin (HbA1c), and fasting plasma glucose (FPG) were similar in both groups. Approximately half of participants in the SGLT-2i-user group and ~ 25% participants in the SGLT-2i-non-user group were on two oral anti-hyperglycemic drugs (OADs), whereas ~ 20% in the SGLT-2i-user group and ~ 1% of participants in the SGLT-2i-non-user group were on three OADs in addition to iGlarLixi. Around 35% and 55% of participants in the SGLT-2i-user and SGLT-2i-non-user groups, respectively, were taking concurrent sulphonylureas. About 97% of participants in both groups were able to fast for ≥ 25 days. The incidence of primary endpoint was low in both groups; SGLT-2i user: 0.6%, 4.2%, and 0.6% and SGLT-2i-non-user: 1.3%, 0.9% and 0% during pre-Ramadan, Ramadan, and post-Ramadan period, respectively. The incidence of severe and/or symptomatic documented (< 54 mg/dl [< 3.0 mmol/l]) hypoglycemia events was also low throughout the study, including during Ramadan. No severe hypoglycemia occurred during Ramadan in either group. Improvements in HbA1c and FPG, with a small reduction in weight, were observed from pre- to post-Ramadan in both groups. No serious adverse event was reported in either group. Conclusions: Concomitant iGlarLixi and SGLT-2i therapy with or without other OADs was demonstrated to be safe in adults with T2D during Ramadan fast, with a low risk of hypoglycemia and improvements in glycemic outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Practice on fasting prior to extubation in critically ill patients is variable. Efficacy of fasting in reducing gastric volume has not been well established. The primary objective of this study was to assess the effect of 4 h of fasting on prevalence of empty stomach using gastric ultrasonography in critically ill subjects who are fasted for extubation. The secondary objectives were to evaluate the change in gastric volumes during 4 h of fasting and to determine factors associated with empty stomach after fasting. METHODS: This was a single-center, prospective, observational study on adult ICU subjects who were enterally fed for at least 6 h continuously and mechanically ventilated. Gastric ultrasound was performed immediately prior to commencement of fasting, after 4 h of fasting, and after nasogastric (NG) aspiration after 4 h of fasting. An empty stomach was defined as a gastric volume ≤ 1.5 mL/kg. RESULTS: Forty subjects were recruited, and 38 (95%) had images suitable for analysis. The prevalence of empty stomach increased after 4 h of fasting (25 [65.8%] vs 31 [81.6%], P = .041) and after 4 h of fasting with NG aspiration (25 [65.8%] vs 34 [89.5%], P = .008). There was a significant difference in median (interquartile range) gastric volume per body weight between before fasting and 4 h after fasting (1.0 [0.5-1.8] mL/kg vs 0.4 [0.2-1.0] mL/kg, P < .001). No patient factors were associated with higher prevalence of empty stomach after 4 h of fasting. CONCLUSIONS: Most mechanically ventilated subjects had empty stomachs prior to fasting for extubation. Fasting for 4 h further increased the prevalence of empty stomach at extubation to > 80%. [ABSTRACT FROM AUTHOR]

Context For Muslim patients on levothyroxine (L-T4) therapy, the best approach for L-T4 intake during Ramadan fasting remains unclear. Objective We compared 2 practical approaches for L-T4 intake during Ramadan. Methods We randomly assigned 69 patients (21 males, 48 females, median age 44 years) with differentiated thyroid cancer (DTC) who underwent thyroidectomy in the past and are on stable LT4 doses to 2 arms. Arm A (33 patients) ingested their pre-Ramadan L-T4 dose at the evening meal and ate immediately. Arm B (36 patients) increased their pre-Ramadan dose by 25 µg if their regular L-T4 dose was ≤150 µg/day or by 50 µg if their pre-Ramadan dose was >150 µg/day and ate immediately. Results At the beginning of Ramadan (baseline), the median thyrotropin (TSH) level and the numbers of patients in euthyroidism, subclinical hyperthyroidism (Shyper), or subclinical hypothyroidism (Shypo) were comparable between the 2 arms (P =.69 and P =.65, respectively). At the end of Ramadan, in arm A there were 17 (51.5%), 3 (9.1%), and 13 (39.4%) patients in euthyroidism, Shyper, and Shypo compared with 17 (47.2%), 14 (38.9%), and 5 (13.9%) patients, respectively, in arm B (P =.005). The mean ± SD TSH levels in arms A and B at the end of Ramadan were 5.6 ± 6.0 mU/L and 1.67 ± 2.6 mU/L, respectively (P =.0001). Conclusion No overt thyroid dysfunction developed but there were more cases of Shypo in arm A and Shyper in arm B. Arm B achieved desirable levels of TSH (normal or slightly suppressed) in 86% of cases and might be a preferable approach, especially for patients who need TSH suppression (eg, DTC). [ABSTRACT FROM AUTHOR]

BACKGROUND Inhibitors of the Na+-coupled glucose transporter SGLT2 (SGLT2i) primarily shift the reabsorption of large amounts of glucose from the kidney's early proximal tubule to downstream tubular segments expressing SGLT1, and the non-reabsorbed glucose is spilled into the urine together with some osmotic diuresis. How can this protect the kidneys and heart from failing as observed in individuals with and without type 2 diabetes? GOAL Mediation analyses identified clinical phenotypes of SGLT2i associated with improved kidney and heart outcome, including a reduction of plasma volume or increase in hematocrit, and lowering of serum urate levels and albuminuria. This review outlines how primary effects of SGLT2i on the early proximal tubule can explain these phenotypes. RESULTS The physiology of tubule-glomerular communication provides the basis for acute lowering of GFR and glomerular capillary pressure, which contributes to lowering of albuminuria but also to long term preservation of GFR, at least in part by reducing kidney cortex oxygen demand. Functional co-regulation of SGLT2 with other sodium and metabolite transporters in the early proximal tubule explains why SGLT2i initially excrete more sodium than expected and are uricosuric, thereby reducing plasma volume and serum urate. Inhibition of SGLT2 reduces early proximal tubule gluco-toxicity and by shifting transport downstream may simulate "systemic hypoxia", and the resulting increase in erythropoiesis, together with the osmotic diuresis, enhances hematocrit and improves blood oxygen delivery. Cardio-renal protection by SGLT2i is also provided by a fasting-like and insulin-sparing metabolic phenotype and, potentially, by off-target effects on the heart and microbiotic formation of uremic toxins. [ABSTRACT FROM AUTHOR]

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Fasting is a common dietary intervention known for its protective effects against metabolic and cardiovascular diseases. While its effects are mostly systemic, understanding tissue-specific changes in the heart is crucial for the identification of the mechanisms underlying fasting-induced cardioprotection. In this study, we performed a proteomic analysis of the fasting heart and attempted to clarify the molecular basis of fasting-induced cardioprotection. Our investigation identified a total of 4,652 proteins, with 127 exhibiting downregulation and 118 showing upregulation after fasting. Annotation analysis highlighted significant changes in processes such as lipid metabolism, the peroxisome pathway, and reactive oxygen species metabolism. Notably, the HIF-1 signaling pathway emerged as one of the focal points, with various HIF-1 targets exhibiting differential responses to fasting. Further experiments demonstrated downregulation of HIF-1α at both transcript and protein levels. Intriguingly, while gene expression of Egln3 decreased, its protein product PHD3 remained unaffected by fasting. The unchanged levels of pro-inflammatory cytokines indicated that the observed reduction in Hif1a expression did not stem from a decrease in basal inflammation. These findings underscore the complex regulation of the well-established cardioprotective HIF-1 signaling within the heart during 3-day fasting. [ABSTRACT FROM AUTHOR]

A randomized, open‐label, 2‐period, 2‐sequence crossover study was conducted to evaluate the pharmacokinetics and bioequivalence of 2 oral formulations of vildagliptin tablets under both fasting and fed conditions in healthy Chinese subjects. A total of 56 healthy subjects were randomized to receive a single 50‐mg dose of either a generic vildagliptin tablet (T) or the reference formulation (R). The washout period was 3 days. Blood samples were collected up to 24 hours postdosing during each period and analyzed for vildagliptin using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The 90% confidence intervals for the geometric mean ratios (T:R) of maximum serum concentration, area under the serum concentration‐time curve from time 0 to the last measurable concentration, and area under the serum concentration‐time curve from time 0 to infinity were all within the predefined bioequivalence range of 80%‐125%. This indicates that the generic and reference formulations are bioequivalent under both fasting and fed states. All adverse events reported were mild and transient. High‐fat meals delayed absorption and reduced the maximum peak concentration of both formulations; however, they did not affect the overall exposure. Therefore, vildagliptin can be taken without regard to meals. [ABSTRACT FROM AUTHOR]

Simple Summary: Diet is a fundamental determinant of health and longevity. This relationship is complex. Historically, among the most investigated variables have been quality and quantity of food. However, over the past 2 decades increasing attention has been devoted to dietary rhythms, including time of food consumption during the day and length of fasting intervals. In this respect, contrasting evidence has recently emerged in the literature regarding the effect of adequate intervals of fasting on the evolution of diet-related chronic liver diseases, including hepatocellular carcinoma. In this review, we briefly refer to this evidence and propose a hypothesis that may help reconcile apparently conflicting observations. Dietary rhythms have emerged as a relevant variable in the equation relating nutrition and health. Both experimental and epidemiological studies point to potential beneficial effects of adequate fasting intervals between meals on the evolution of chronic diseases associated with aging. Metabolic dysfunction-associated steatotic liver disease (MASLD) is eminently related to diet and unsurprisingly, diet-based approaches are a mainstay in countering its long-term clinical evolution, including the emergence of hepatocellular carcinoma (HCC). We briefly discuss current evidence linking fasting intervals, MASLD, and HCC and propose a working hypothesis to reconcile some of the apparently conflicting results. This hypothesis relates the beneficial effects of time-restricted eating schedules to the quantity and quality of food, and it is easily amenable to testing. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity induces insulin resistance (IR) and metabolic imbalances before any significant changes in adiposity. Recent studies suggest that the beneficial effects of exercise can be potentiated if performed while fasting. This work aimed to compare the subacute effects of fed- and fasted-state single-bout exercise on biochemical parameters and cellular signaling in the metabolism. Methods: The animals were allocated into fed rest (FER), fasting rest (FAR), fed exercise (FEE), and fasting exercise (FAE) groups. The exercise protocol was a 30 min treadmill session at 60% of V ˙ O2max. The fasting groups fasted for 8 h before exercise and were killed after 12 h post-exercise. Results: Soleus glycogen concentration increased only in the fasting groups, whereas the triglyceride (TGL) content increased in brown adipose tissue (BAT) and liver in the FAE. The FAE showed decreased plasma total cholesterol concentration compared withthe FAR group. Immunocontent of HSP70, SIRT1, UCP-1, and PGC1-α did not change in any tissue investigated. Conclusions: Our results indicate that physical exercise while fasting can have beneficial metabolic effects on sedentary animals. Remarkably, in the FAE group, there was a reduction in total plasma cholesterol and an increase in the capacity of BAT to metabolize and store nutrients in the form of TGLs. [ABSTRACT FROM AUTHOR]

Buckwheat grains contain bioactive components with known effects on cardiometabolic biomarkers. Previous research on oxidative stress markers made exclusively from wheat flour or two-hour postprandial levels of antioxidant status, plasma total polyphenols, and advanced glycation end products (AGEs) were considerably higher than fasting values after consuming buckwheat-incorporated bread (BWB), including clinical, animal, and epidemiological studies, suggesting the potential of buckwheat intake to influence parameters such as polyphenol intake, antioxidant status, insulin levels, and oxidative stress markers. However, the specific impact of buckwheat-containing bread on these biomarkers in individuals with type-II diabetes remains a significant gap in our understanding. Our current work aims to address this gap by exploring the effects of buckwheat-containing bread on insulin levels, polyphenol intake, antioxidant status, and markers of oxidative stress. In a randomized crossover study, 16 individuals with type-II diabetes were assigned to consume control bread made exclusively from wheat flour or bread incorporating 50% buckwheat flour. The research followed a crossover design, with a period of one to two washout interventions. Test breads were given at breakfast following a 12 h fast the previous night. After 2 h of bread intake, blood samples were collected at baseline (fasting). The two-hour postprandial levels of antioxidant status, plasma total polyphenols, and advanced glycation end products (AGEs) were significantly higher than fasting values after consuming buckwheat-incorporated bread (BWB). This suggests that the buckwheat-containing bread improved plasma total polyphenol levels and total antioxidant status. Our research concludes that the intake of bread containing buckwheat positively influences polyphenols in plasma and the status of antioxidants. This suggests that incorporating buckwheat into bread may have favorable effects on biomarkers associated with cardio-metabolic health in individuals with type-II diabetes. By addressing these knowledge gaps, our research aims to inform and engage the scientific community in further exploration of the potential health benefits of buckwheat-containing bread. [ABSTRACT FROM AUTHOR]

Introduction Diabetes is a chronic metabolic disorder characterized by impaired insulin secretion and action. Risk factors for diabetes include age, obesity, low physical activity, hypertension, lipid disorders, and genetic predisposition. Symptoms of diabetes typically include frequent urination, weight loss, excessive thirst, weakness, fatigue, susceptibility to fungal infections and recurrent boils. Diabetes is a prevalent and significant societal concern, often causing anxiety, uncertainty and a sense of danger upon diagnosis. Aim of the study The aim of the study is to provide a comprehensive analysis of diabetes, including its classification, characteristic symptoms, the most frequently occurring diabetes-related complications, and preventive strategies. Through a detailed discussion of these issues, our goal is to increase public awareness of diabetes and provide readers with comprehensive knowledge about this disease. Material and method This article presents the current state of knowledge about diabetes. A literature review was conducted using the PubMed, Google Scholar and Web of Science databases, utilizing keywords such as "diabetes", "diabetes mellitus", "diabetes complications". Results The number of people with diabetes has continued to rise. Scientists predict that in a few decades, this number could reach more than half a billion globally. Many individuals may not realize that they are at risk for this civilization disease, often due to unhealthy lifestyle choices such as smoking, obesity, and lack of physical activity. Early initiation of treatment is crucial in preventing serious complications. Despite living with diabetes for years, some patients still report insufficient knowledge about their condition. Therefore, educating patients about the nature of the disease and its treatment is essential for improving their quality of life. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in biochemical parameters and changes in eating habits are considered complications of obesity. Oleoylethanolamide (OEA), an endocannabinoid-like compound, has been shown to have protective effects on many metabolic disorders. Given this evidence, the present study aimed to assess the effects of OEA on lipid profile parameters, fasting blood sugar (FBS), and dietary habits in healthy obese people. Methods: In this randomized, double-blind, placebo-controlled clinical trial, which was carried out in 2016 in Tabriz, Iran, 60 obese people were enrolled in the study based on inclusion criteria. The intervention group consumed 125 mg of OEA capsules, and the placebo group received the same amount of starch twice for 8 weeks. Blood samples (5 mL) were taken at baseline and the end of the study in a fasting state. Serum concentrations of FBS, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) were measured by enzymatic methods using commercial kits. The low-density lipoprotein cholesterol (LDL-C) concentration was obtained using the Friede-Wald formula. To assess dietary habits, a food frequency questionnaire (147 items) was used at baseline and the end of the study. A value less than < 0.05 was considered to indicate statistical significance. Results: The TG concentration decreased significantly in the intervention group (mean (SD): 166.29 (70.01) mg/dL to 142.22 (48.05) mg/dL, p = 0.047). Changes in the placebo group were not significant (p > 0.05). After adjusting for baseline values and demographic characteristics, the difference in TG between groups remained significant (p = 0.044). Changes in other biochemical parameters were not significant. There was no significant difference between or within groups in terms of food groups. Conclusion: OEA, as a complementary agent, plays a protective role in TG regulation. However, future studies with longer durations are needed to explore the impact of OEA on regulating dietary habits and to identify the mechanisms related to metabolic abnormalities in obese people. Trial Registration: The study was registered in the Iranian Registry of Clinical Trials (IRCT) center as IRCT201607132017N30 with URL. www.IRCT.IR in date 03/10/2016. [ABSTRACT FROM AUTHOR]

Objective: The present study objectived to investigate the influence of Ramadan fasting (RF) on olfactory function. Methods: Sixty‐two participants were included in the current prospective study. The odor threshold and identification performances were determined by using the Connecticut Chemosensory Clinical Research Center (CCCRC) test initially (day 0) and on the first and last day (30th) of RF. Body weight (BW)s were measured initially and at the end of the study. The results were analyzed statistically. Results: The average of baseline and last‐day BWs were 78.38 ± 12.96 and 78.36 ± 12.39 kg, respectively. No significant difference was determined in terms of BWs (p =.932, p >.05). In the evaluation of CCCRC test outcomes, significant differences were observed in the scores of butanol thresholds (p =.0001), odor identification (p =.0001), food‐related odors identification (p =.0001), and the number of normosmic individuals (p =.0001) at different times (p <.05). The thresholds scores (p =.0001, p =.0001), the identification scores (p =.0001, p =.0001), food‐related odors identification scores (p =.0001, p =.0002), and the number of normomic individuals (p =.001, p =.001) detected on 30th day were significantly higher than on 0th and 1st days; respectively (p <.05). Additionally, the threshold scores (p =.0001), the identification scores (p =.003), food‐related odors identification scores (p =.007), and the number of normosmic individuals (p =.018) detected on day 1 were significantly higher than on day 0 (p <.05). Conclusion: The current study demonstrated that Ramadan fasting enhances the olfactory detection threshold and odor identification scores, significantly improving the identification of food‐related odors. The results may indicate that Ramadan fasting improves olfactory performance. Level of evidence: Level II. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is one of the complications of diabetes. This study was conducted to investigate the effect of curcumin-piperine on laboratory factors and macular vascular in DR. Materials and Methods: The present study was a randomized, placebo-controlled, double-blind, parallel-arm clinical trial that was conducted on 60 patients with DR aged 30-65 years. Patients were randomized into two groups to receive (i) 1010 mg/day of curcumin-piperine (two tablets per day, each tablet containing 500 mg curcuminoids and 5 mg piperine) (n = 30) or (ii) the matched placebo (n = 30) for 12 weeks. The investigated factors included optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), oxidative stress factors, C-reactive protein (CRP), fasting blood glucose (FBG), triglycerides (TGs), blood urea nitrogen (BUN), and creatinine. Results: The trial was completed by 27 patients in the intervention group and 29 patients in the placebo group. Curcumin-piperine significantly increased total antioxidant capacity (0.86 ± 0.66 vs. 0.45 ± 0.89; P = 0.022) and superoxide dismutases (0.77 ± 2.11 vs. -0.45 ± 3.08; P = 0.031), while it decreased and malondialdehyde (MDA) (-1.06 ± 5.80 vs. 1.89 ± 6.12; P = 0.043) and creatinine (-0.04 ± 0.16 vs. 0.03 ± 0.05; P = 0.042) compared with placebo. However, this supplement had no significant effect on CRP, FBG, TG, BUN, OCT, and OCTA. There were no adverse reactions. Conclusion: Curcumin-piperine is effective in improving oxidative stress and reducing creatinine in DR. Further trials are necessary to confirm these promising findings. [ABSTRACT FROM AUTHOR]

Background: A mismatch between biological and social time, often referred to as social jetlag (SJL), can lead to inadequate sleep and activities or taking meals at times that do not align with our biological rhythms, increasing the risk of metabolic abnormalities. Although the association between sleep and metabolic syndrome (MetS) is well established, the effects of SJL on MetS and the components of MetS in adults remain unclear. Purpose: This study was designed to explore the relationship between SJL and MetS components in adults. Methods: A systematic review and meta-analysis was conducted on studies registered in PubMed, Cochrane, Web of Science, and Embase between the inception of each database until November 15, 2023.We focused on studies designed to evaluate the relationship between SJL and either MetS or its components. Only studies using cross-sectional, prospective, or retrospective designs were considered for inclusion. The relationship between SJL and MetS was depicted as an odds ratio with a corresponding 95% confidence interval (CI). We determined the mean differences and 95% CIs to estimate the associations between SJL and MetS components. The Joanna Briggs Institute Critical Appraisal Checklist was used to evaluate the methodological rigor of the selected studies. Data were analyzed using RevMan software Version 5.4. Results: The systematic review included 16 studies, with five analyzed via a meta-analysis covering four outcomes, each based on two to three studies. When comparing SJL of less than 1 hour with SJL of 2 hours or more, the latter showed a higher likelihood of MetS (pooled odds ratio: 1.52). Although a significant decrease in systolic blood pressure (pooled mean differences = −3.52 mmHg, 95% CI [−6.41, −0.64]) and a significant increase in waist circumference (pooled mean differences = 2.17 cm, 95% CI [0.61, 3.73]) were observed, the correlation between SJL and diastolic blood pressure failed to reach statistical significance. Conclusions/Implications for Practice: The meta-analysis conducted in this study found an association between SJL and MetS. Healthcare practitioners should prioritize the management of sleep quality and duration, especially for individuals exhibiting substantial SJL. Improving sleep can aid in controlling blood pressure and managing weight and should form part of MetS management strategies. [ABSTRACT FROM AUTHOR]

Contrast-enhanced tomographic studies via intravenous contrast are increasingly common. However, delays in their execution often occur due to the lack of fasting and concerns regarding associated risks. Objective: To demonstrate the safety of conducting contrast-enhanced tomographic studies in subjects without fasting. Method: A retrospective study analyzing abdominal tomographic scans using intravenous contrast. Subjects were categorized based on fasting/non-fasting status, and adverse events were recorded. Results: A total of 542 tomographic scans were analyzed, with 40.2% complying with fasting requirements. All studies were completed successfully. The gender distribution was similar, with a median age of 47 years (IQR: 33-60). No adverse events or complications were observed in either group. Conclusions: Preceding fasting for a contrast-enhanced tomographic study using intravenous contrast does not influence the occurrence of adverse effects or complications. [ABSTRACT FROM AUTHOR]

Long-term fasting (LTF) and caloric restriction (CR) have garnered increasing interest as interventions that may confer numerous health benefits, including improved metabolic health, enhanced cardiovascular function, neuroprotection, and extended longevity. The potential to influence physiological processes such as insulin sensitivity, lipid metabolism, inflammation, oxidative stress, and cellular repair mechanisms makes these interventions promising avenues for both disease prevention and health optimization. This systematic review examines the body of research surrounding LTF and CR, their physiological impacts, the molecular mechanisms driving these changes, and the challenges and risks associated with their long-term application. We also explore future research directions and possible therapeutic applications in the context of aging and age-related diseases. [ABSTRACT FROM AUTHOR]

What mechanisms can link the inhibition of sodium-glucose cotransporter 2 (SGLT2) in the early proximal tubule to kidney and heart protection in patients with and without type 2 diabetes? Due to physical and functional coupling of SGLT2 to other sodium and metabolite transporters in the early proximal tubule (including NHE3, URAT1), inhibitors of SGLT2 (SGLT2i) reduce reabsorption not only of glucose, inducing osmotic diuresis, but of other metabolites plus of a larger amount of sodium than expected based on SGLT2 inhibition alone, thereby reducing volume retention, hypertension and hyperuricemia. Metabolic adaptations to SGLT2i include a fasting-like response, with enhanced lipolysis and formation of ketone bodies that serve as additional fuel for kidneys and heart. Making use of the physiology of tubulo-glomerular communication, SGLT2i functionally lower glomerular capillary pressure and filtration rate, thereby reducing physical stress on the glomerular filtration barrier, tubular exposure to albumin and nephrotoxic compounds, and the oxygen demand for reabsorbing the filtered load. Together with reduced gluco-toxicity in the early proximal tubule and better distribution of transport work along the nephron, SGLT2i can preserve tubular integrity and transport function and, thereby, glomerular filtration rate in the long-term. By shifting transport downstream, SGLT2i may simulate systemic hypoxia at the oxygen sensors in the deep cortex/outer medulla, which stimulates erythropoiesis and, together with osmotic diuresis, enhances hematocrit and thereby improves oxygen delivery to all organs. The described SGLT2-dependent effects may be complemented by off-target effects of SGLT2i on the heart itself and on the microbiome formation of cardiovascular-effective uremic toxins. [ABSTRACT FROM AUTHOR]

Summary Circadian disruption, arising from conflict between internal circadian time and behavioural sleep–wake and fasting–feeding rhythms, may contribute to the prevalence of type 2 diabetes mellitus and disease severity. Previous studies have demonstrated a link between irregular breakfast eating and poorer metabolic health. We aimed to further explore the relationships between breakfast habits, circadian misalignment (social jetlag), and metabolic parameters in a cohort of adult participants with type 2 diabetes mellitus. A total of 330 adult participants with type 2 diabetes mellitus attending for routine clinical review completed structured questionnaires to assess habitual sleep timing, chronotype, and social jetlag. Statistical analysis was via inferential groupwise approaches and path analysis to establish interdependencies of effects of social jetlag, chronotype, and breakfast eating regularity on HbA1c. 22.7% of the participants reported eating breakfast five times or fewer a week, and were categorised as irregular breakfast eaters. Compared with those who ate breakfast six or seven times a week, irregular breakfast eaters had significantly higher HbA1c and diastolic blood pressure, were younger and had greater social jetlag. In the path analysis, irregular breakfast eating exerted a direct effect on HbA1c, whilst social jetlag exerted only an indirect effect on HbA1c through breakfast eating regularity. Chronotype did not exert any effect on HbA1c, but did exert an indirect effect on breakfast eating regularity via social jetlag. Our results showed that adult participants with type 2 diabetes mellitus, who ate breakfast irregularly had poorer metabolic health and greater social jetlag. The relationship between social jetlag and glycaemic control appears to be mediated through breakfast eating habits. [ABSTRACT FROM AUTHOR]

• People with obesity plus prediabetes or T2DM had elevated metabolic dysregulation. • Those with prediabetes or T2DM had decreased vitamin C status. • This was despite comparable dietary intakes to those without diabetes. • Vitamin C status was inversely associated with metabolic dysregulation. • Thus, metabolic dysregulation is associated with an increased demand for vitamin C. Obesity and diabetes are known to negatively affect vitamin C status. However, whether the presence of diabetes, in addition to obesity, contributes an additional impact on vitamin C status is currently uncertain. In a cohort of 152 adults living with obesity, we assessed metabolic and nutrient parameters in participants without diabetes (n = 92), and with prediabetes (n = 22) and type 2 diabetes mellitus (T2DM; n = 35). Vitamin C concentrations were measured in plasma and leukocytes using HPLC and vitamin C intakes were assessed using 24-hour dietary recall. Metabolic severity scores were derived using gender, ethnicity, height, weight, waist circumference, systolic blood pressure, fasting glucose, HDL, and triglyceride values. In people living with obesity, those with prediabetes and T2DM had increased metabolic dysregulation and decreased vitamin C status relative to those without diabetes (P <.05). Vitamin C deficiency was observed in a high proportion (23%-32%) of participants with prediabetes and T2DM and ≥50% had hypovitaminosis C. However, there was no difference in vitamin C intake between those without diabetes and those with prediabetes or T2DM (P >.05). There was a significant inverse correlation between plasma vitamin C status and metabolic severity score (r = -0.290, P <.001). Linear regression indicated that for every 1-unit increase in metabolic severity score, there was a 6.5 µmol/L decrease in vitamin C status. Thus, the enhanced metabolic dysregulation observed with prediabetes and T2DM is associated with an increased demand for vitamin C in people living with obesity. In people living with obesity, those with prediabetes (orange circles) and type 2 diabetes mellitus (T2DM; red circles) had increased metabolic dysregulation and decreased plasma vitamin C status relative to those without diabetes (green circles). For every 1-unit increase in metabolic severity score, there was a 6.5 µmol/L decrease in plasma vitamin C status. [Display omitted] [ABSTRACT FROM AUTHOR]

Dihydroxyaluminum aminoacetate, heavy magnesium carbonate, and aspirin tablets is a new combined aspirin preparation, each containing aspirin (81 mg), dihydroxyaluminum aminoacetate (11 mg), and heavy magnesium carbonate (22 mg). This study was conducted to evaluate the pharmacokinetic (PK) and bioequivalence in healthy Chinese subjects. This randomized, open‐label, single‐dose, 2‐sequence, and 2‐period crossover study included 78 healthy volunteers (fasting, n = 36; postprandial, n = 42). Blood samples were collected for PK analysis. Aspirin and salicylic acid concentrations in human plasma were determined by liquid chromatography‐tandem mass spectrometry. Safety and tolerability were monitored. There were no significant differences between the test and reference formulations in maximum plasma concentration, area under the plasma concentration‐time curve (AUC) from time 0 to time t, or AUC from time 0 to infinity. The 90% confidence intervals of the test and reference formulations of maximum plasma concentration, AUC from time 0 to time t, and AUC from time 0 to infinity were within the acceptable range (80%‐125%) under fasting and postprandial conditions. All adverse events were mild and no serious adverse events were observed in the study. Both compounds were well tolerated in healthy Chinese volunteers. [ABSTRACT FROM AUTHOR]

A major form of meat abstinence in modern China was the observance of periodic fasting, as distinct from permanent vegetarianism. This article explores the various forms of such observances and their evolution from late imperial times to the Republican period. It describes the religious calendars that circulated widely from the late Qing onward and identifies the most common fasting regimens (and the associated gods) that people selected from a large choice of fasting days. It then draws on narrative material to tease out how and why people adopted such regimens and to discuss debates and polemics about them. Finally, it shows that periodic fasting continued to be popular during the twentieth century, exhibiting more continuities than current studies of modern changes in the discourses about vegetarianism would suggest. [ABSTRACT FROM AUTHOR]

This study determined the associations of apolipoprotein A1 (ApoA1), high-density lipoprotein cholesterol (HDL-C), and HDL-C/ApoA1 ratio with fasting blood glucose (FBG) and evaluated the mediating effects of high-sensitivity C-reactive protein (hsCRP) and body mass index (BMI). A cross-sectional study with 4805 coronary artery disease (CAD) patients was performed. In multivariable analyses, higher ApoA1, HDL-C, and HDL-C/ApoA1 ratio were associated with significantly lower FBG level (Q [quartile] 4 vs Q1: 5.67 vs 5.87 mmol/L for ApoA1; 5.64 vs 5.98 mmol/L for HDL-C; 5.63 vs 6.01 mmol/L for HDL-C/ApoA1 ratio). Moreover, inverse associations of ApoA1, HDL-C, and HDL-C/ApoA1 ratio with abnormal FBG (AFBG) were found with odd ratios (95% confidence interval) of.83 (.70–.98),.60 (.50–.71), and.53 (.45–.64) in Q4 compared with Q1. Path analyses indicated that "ApoA1 (or HDL-C)-FBG" associations were mediated by hsCRP and "HDL-C-FBG" association was mediated by BMI. Our data suggested that higher ApoA1, HDL-C, and HDL-C/ApoA1 ratio were favorably associated with a lower FBG level in CAD patients and these associations might be mediated by hsCRP or BMI. Collectively, higher concentrations of ApoA1, HDL-C, and HDL-C/ApoA1 ratio might decrease the risk of AFBG. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated glycemic outcomes for hospitalized patients after reduction in bedtime correctional insulin dosing. Methods: This was a retrospective, single-center analysis of a protocol change that reduced bedtime correctional insulin scale. Comparable cohorts pre- and post-protocol change were created which included patients who were ordered correctional insulin with at least 1 blood glucose (BG) reading. The primary outcome was number of nocturnal hypoglycemia readings. Secondary outcomes included, but were not limited to, mean fasting BG, BG within various ranges, and length of stay. Results: 3 percent of patients in the post-protocol change group (N = 100) experienced nocturnal hypoglycemia compared to 6% of patients in the pre-change group (N = 100) (P =.507). There were no significant differences in BG ranges <110 mg/dL, <140 mg/dL, 140 to 180 mg/dL, and >180 mg/dL. However, 19% of patients in the post-protocol change group had BG of >250 mg/dL as compared to 9% in the pre-change group (P =.033). Mean fasting BG was higher in the post-protocol change group compared to the pre-change group (156.5 mg/dL vs 139.3 mg/dL [ P =.002]), as was hospital length of stay (5.17 vs 4.6 days, [ P =.024]). Conclusions: A decreased bedtime correctional insulin scale had mixed results with more patients achieving goal fasting BG but also more patients experiencing BG > 250 mg/dL and longer length of stay. Larger prospective studies are required to evaluate the safety and efficacy of this type of intervention and its long-term impact. [ABSTRACT FROM AUTHOR]

In recent times, dietary restriction (DR) has received considerable attention for its promising effects on metabolism and longevity. Previous studies on DR have mainly focused on the health benefits produced by different restriction patterns, whereas comprehensive reviews of the role of gut microbiota during DR are limited. In this review, we discuss the effects of caloric restriction, fasting, protein restriction, and amino acid restriction from a microbiome perspective. Furthermore, the underlying mechanisms by which DR affects metabolic health by regulating intestinal homeostasis are summarized. Specifically, we reviewed the impacts of different DRs on specific gut microbiota. Additionally, we put forward the limitations of the current research and suggest the development of personalized microbes-directed DR for different populations and corresponding next-generation sequencing technologies for accurate microbiological analysis. DR effectively modulates the composition of the gut microbiota and microbial metabolites. In particular, DR markedly affects the rhythmic oscillation of microbes which may be related to the circadian clock system. Moreover, increasing evidence supports that DR profoundly improves metabolic syndrome, inflammatory bowel disease, and cognitive impairment. To summarize, DR may be an effective and executable dietary manipulation strategy for maintaining metabolic health, however, further investigation is needed to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

The liver of mammals is a critical organ that houses numerous physiological processes, including macronutrient metabolism. Regarding nutrient metabolism, the liver shows a quick response to nutrient status fluctuation, such as feeding and fasting. Indeed, fasting is a powerful tool to uncover the molecular mechanism through which the expression of hepatic genes is regulated. The most widely applied approach to test gene expression at the RNA level is relative quantitative polymerase chain reaction (qPCR) using stably expressed genes as an internal reference. In this study, we leveraged transcriptomic analysis to screen the hepatic genes whose expression levels were stable in response to fasting. Our data suggested that expression levels of several well-known reference genes such as beta-actin and Eef1a1 are dramatically altered upon fasting. Further assessment indicated that Itm2b is the most stably expressed hepatic gene showing no alteration to fasting. Compared to beta-actin and Eef1a1, similar results and conclusions as transcriptomic analysis were obtained using Itm2b as an internal reference in qPCR when we assessed the effect of fasting on the expression of genes involved in peroxisomal fatty acid oxidation, fatty acid synthesis, and gluconeogenesis. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading causes of global mortality. Modifiable behavioural and metabolic risk factors significantly contribute to the burden of CVD. Given the vast socio-demographic and health outcome heterogeneity in Latin America, similar southern Latin American countries (Argentina, Chile, and Uruguay) were analysed as a distinct group to describe the CVD death rates related to metabolic and behavioural risk factors. An ecological study was performed using data from the Global Burden of Disease Study 2019. Metabolic and behavioural risk factors-related CVD death were examined by analysing age-standardised rates per 100,000 individuals in the three countries between 1990 and 2019. While exposure to behavioural risk is decreasing, an upwards trend was observed in metabolic risks. Among the assessed risk factors, metabolic factors emerged as the primary contributors to deaths. High fasting plasma glucose exhibited a remarkable increase in relative importance across most studied contexts. Dietary risks stood out among behavioural factors due to their complexity and substantial changes observed. Although mortality rates have declined for overall CVD, peripheral artery disease mortality is rising. Modifiable behavioural and metabolic risk factors significantly influence CVD mortality in Southern Latin America. Despite the increasing exposure to metabolic risks, advancements in prevention and treatment are evidenced in the decline of mortality rates for most CVD. These findings emphasise the need for targeted interventions and comprehensive strategies to address their impact on cardiovascular health, advocating for healthy lifestyle behaviours to mitigate the progression and CVD development. • What is the cardiovascular disease burden from modifiable behavioural and metabolic risk factors in Southern Latin America? • Metabolic risks drove cardiovascular deaths: blood pressure was most significant and fasting glucose increased the most. • Focused prevention and treatment strategies targeting these factors can enhance life quality and expectancy. [ABSTRACT FROM AUTHOR]

Objective. To compare the prevalence and trajectories of risky health behaviors in sexual minority (SM; lesbian/gay/bisexual/questioning/asexual) versus heterosexual undergraduates across their first year of post-secondary. Participants. First-year undergraduates (N = 704, Mage=17.97 years, 24% SM) from a midsized Canadian university. Methods. Students completed monthly (September-April) online questionnaires assessing substance use (binge drinking, tobacco, cannabis, illicit drug use) and disordered eating (binge eating, fasting, purging). Results. At the outset of the academic year, SM students endorsed more frequent cannabis use, illicit drug use, fasting, and binge eating, but less frequent tobacco use, versus heterosexual students. Over the year, SM students' binge drinking frequency declined less than that of heterosexual students, but their illicit drug use decreased while that of their heterosexual peers increased, and all students reported declining disordered eating frequency. Conclusions. Campus wellness initiatives for SM students should offer prevention and harm-reduction strategies prior to or shortly after their arrival on campus. [ABSTRACT FROM AUTHOR]

Introduction Studies link hypovitaminosis D to be significantly associated with poor glycemic control, heightened inflammation, and risk of complications. Studies recommend fasting or calorie restriction as a useful measure to achieve diabetic reversal. The present study explores if therapeutic fasting is associated with improvement in the vitamin D levels and other clinical outcomes related to type 2 diabetes mellitus (T2DM). Methods This observational study included 26 T2DM patients exposed to a 10-day medically supervised fasting (≈ 500–1000 Kcal/day) in a complementary medicine facility. Levels of vitamin D, B12, fasting blood sugar (FBS), blood pressure, anthropometric measures, World Health Organization Quality of Life, disease perception (Brief Illness Perception Questionnaire), and self-reported vitality were measured at the baseline and the 10th day. Results Significant improvement in the levels of vitamin D (p = 0.000), B12 (p = 0.03), and reduction in FBS levels (p = 0.001), blood pressure, body mass index, waist and hip circumference (p ≤ 0.05), and improvement in quality of life, vitality, and disease perception (p < 0.001) were observed by the end of 10th day. FBS shared a negative correlation with vitamin D levels (males r = –0.1, females r = –0.48). Conclusion The present findings provide insights into the probable mechanisms by which therapeutic fasting modulates the progression of T2DM. Nevertheless, large-scale randomized controlled trials are warranted to validate the present findings. [ABSTRACT FROM AUTHOR]

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Objective: One of the main features of polycystic ovary syndrome (PCOS) is increased adipose tissue, which can result in hormonal disturbances. In the present study, we aimed to investigate which indicator of obesity could better associate with hormonal disturbances in PCOS women. Methods: In this cross-sectional analysis, women with PCOS were included according to the Rotterdam criteria. Fasting blood samples were analyzed for biochemical, metabolic, and hormonal parameters. Anthropometric measures comprised body composition indices (assessed by bioelectric impedance analysis [BIA]), waist circumference, body mass index (BMI), and waist-to-height ratio (WHtR). Linear regression modeling was used to assess the association between anthropometric indices and hormonal imbalance, adjusted for age, mensuration status, and the homeostasis model assessment-estimated insulin resistance (HOMA-IR). Receiver operating characteristics (ROC) curves were utilized to ascertain the sensitivity, specificity, and optimal cut-off points of various anthropometric indices in identifying hyperandrogenism. Results: A total of 129 PCOS women with a median (interquartile range [IQR]) age of 32.0 (23.0–32.0) years and a median BMI of 26.3 (23.00-29.70) kg/m2 were enrolled. In the adjusted linear regression model, BMI (β = 0.053, P < 0.001), waist circumference (β = 0.021, P = 0.001), WHtR (β = 3.325, P = 0.002), total fat mass (β = 0.021, P = 0.002), trunk fat mass (β = 0.038, P = 0.006), and leg fat mass (β = 0.045, P = 0.004) were positively associated with free androgen index (FAI). In addition, BMI (β=−0.017, P = 0.003), waist circumference (β=−0.008, P = 0.002), WHtR (β=−1.167, P = 0.004), total fat mass (β=−0.008, P=0.003), trunk fat mass (β=−0.017, P=0.001), and leg fat mass (β=−0.018, P=0.004) were negatively associated with the serum level of sex hormone binding globulin (SHBG). WHtR showed the greatest area under the curve (AUC) value (AUC = 0.676, P = 0.001) for identifying hyperandrogenism (FAI ≥ 4.97 or total testosterone ≥ 0.7 ng/mL) in PCOS women with corresponding sensitivity of 87.30% and specificity of 39.70%. Conclusions: WHtR is related to hyperandrogenism in PCOS better than other anthropometric measures. [ABSTRACT FROM AUTHOR]

Every-other-day fasting (EODF) is a form of caloric restriction that alternates between periods of normal eating and fasting, aimed at preventing and treating diseases. This approach has gained widespread usage in basic research on neurological conditions, including spinal cord injury, and has demonstrated significant neuroprotective effects. Additionally, EODF is noted for its safety and feasibility, suggesting broad potential for application. This study aims to evaluate the therapeutic effects of EODF on spinal cord injury and to investigate and enhance its underlying mechanisms. Initially, the SCI rat model was utilized to evaluate the effects of EODF on pathological injury and motor function. Subsequently, considering the enhancement of metabolism through EODF, bile acid metabolism in SCI rats was analyzed using liquid chromatography-mass spectrometry (LC-MS), and the expression of the bile acid receptor TGR5 was further assessed. Ultimately, it was confirmed that EODF influences the activation of microglia and NLRP3 inflammasomes associated with the TGR5 signaling, along with the expression of downstream pyroptosis pathway related proteins and inflammatory cytokines, as evidenced by the activation of the NLRP3/Caspase-1/GSDMD pyroptosis pathway in SCI rats. The results demonstrated that EODF significantly enhanced the recovery of motor function and reduced pathological damage in SCI rats while controlling weight gain. Notably, EODF promoted the secretion of bile acid metabolites, activated TGR5, and inhibited the NLRP3/Caspase-1/GSDMD pyroptosis pathway and inflammation in these rats. In summary, EODF could mitigate secondary injury after SCI and foster functional recovery by improving metabolism, activating the TGR5 signaling and inhibiting the NLRP3 pyroptosis pathway. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver (MASLD) disease is the commonest hepatic cause of liver fibrosis and cirrhosis after the introduction of the direct acting antivirals and eradication of hepatitis C. MASLD is usually associated with metabolic syndrome and elevated inflammatory markers. Magnetic resonance spectroscopy (MRS) offers a non-invasive diagnostic, alternative to liver biopsy. This is a case–control diagnostic-accuracy study conducted on 40 patients in the Hepato-gastroenterology Unit in the Internal Medicine Department, Ain Shams University Hospitals, to study the role of MRI spectroscopy as a new diagnostic model for assessment of liver steatosis in non-diabetic MASLD patients compared to the standard ultrasound and clinical criteria. MASLD was diagnosed by a combination of a validated ultrasound hepatic steatosis score grading system and hepatic steatosis index using clinical and laboratory parameters. MRS was performed in all patients and fat peak, water peak, and fat fraction % were measured, and diagnostic accuracy of different MRS is compared to the US scoring and different laboratory and clinical parameters. To our knowledge this is the first study conducted on MRS in our region and Egypt. Results: This study revealed no statistically significant difference between the two groups regarding HbA1C, creatinine, while there was highly statistically significant difference regarding fasting blood sugar, 2 h post-prandial glucose level, urine albumin, and low-density lipoprotein levels. Hepatic steatosis score grading by abdominal ultrasound on the 20 controls showed no fatty changes with grade 0 (50%), and on the 20 MASLD patients showed that 2 cases were grade 1 steatosis (5%), 9 cases were grade 2 steatosis (22.5%), and 9 cases were grade 3 steatosis (22.5%). The diagnostic accuracy of predicting hepatic steatosis using different MRS parameters: fat peak, water peak, and fat fraction had area under the curve of 99.9%, 88.6%, and 100%, respectively. The sensitivity and specificity of fat fraction in detecting hepatic steatosis were 100%. The sensitivity and specificity of the fat peak in detecting hepatic steatosis were 100% and 95%, respectively. Moreover, the sensitivity and specificity of the water peak in detecting the hepatic steatosis were 88.6% and 85%, respectively. There is a statistically significant correlation between the three MRS parameters and the abdominal ultrasound hepatic steatosis score grades. Conclusion: MRS parameters: fat fraction, fat peak, and water peak, have high diagnostic accuracy for predicting the liver steatosis. Moreover, MRS has the added advantage of being a non-invasive and a tool with low radiation risk. MRS also shows the metabolic changes in the liver and could be an eligible outcome in therapeutic clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Food is a vital human need, and the human visual system is finely tuned to detect and respond to food cues in the environment. The omnipresence of food cues across various settings has been linked to the prevalence of obesity in susceptible populations. However, the influence of the post-prandial state on visual attention to food stimuli remains poorly understood. This study aimed to elucidate how a 12 hour fast affects visual attention to food and non-food stimuli in healthy, non-obese individuals. Methods: Visual attention was assessed by measuring the total duration of visual fixations on stimuli presented on a computer screen, using a screen-based eye tracker (Tobii X2-60). Participants were divided into two groups: those who had fasted for 12 hours and those tested within two hours after consuming breakfast (satiated state). Additionally, performance on the Food Stroop task and electrodermal activity (EDA) responses were measured to evaluate attentional interference and physiological arousal, respectively. Salivary samples were also collected to assess levels of alpha-amylase and cortisol. Results: Fasted participants exhibited a progressive decline in visual attention toward food stimuli compared to satiated individuals, reflecting a satiated state. This effect was independent of the palatability of the depicted food items and was not observed with stimuli representing non-food items. The Food Stroop task revealed no differences between fasting and satiated participants, indicating that the presence of food-related stimuli does not differentially impact attentional interference under varying hunger states. Moreover, no significant variations were observed in EDA responses across participant groups and stimulus types, suggesting that the modulation of visual attention to food cues by hunger is independent of physiological arousal. Interestingly, satiated subjects exhibited higher levels of salivary alpha-amylase, which was inversely related to their subjective hunger ratings. No differences in salivary cortisol levels were found between groups. Discussion: The findings indicate a novel influence of mild hunger on the processing of visual food cues, independent of physiological arousal. The decline in visual attention to food stimuli in fasted individuals suggests that satiety modulates visual processing. The lack of differences in attentional interference and physiological arousal between fasting and satiated states further supports the notion that visual attention to food cues is primarily driven by hunger-related mechanisms rather than stress. Additionally, the inverse relationship between salivary alpha-amylase levels and hunger ratings implies that alpha-amylase may serve as a marker of satiety rather than stress. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a hormonal disorder that affects 6–12% of United States women of reproductive age. Because women with PCOS are at an increased risk of developing type 2 diabetes, clinical practice guidelines from a number of organizations (e.g. American Diabetes Association, American College of Obstetricians and Gynecologists, US Preventive Services Task Force) recommend that individuals with PCOS are routinely screened for diabetes. Guidelines further indicate that an oral glucose tolerance test (OGTT) should be used for diabetes screening in women with PCOS as opposed to an A1C or fasting plasma glucose test. The purpose of this study is two-fold: 1) to estimate rates of diabetes screening among a nationwide sample of commercially insured women with PCOS and 2) to report the percentage of women screened using each test (OGTT, A1C, fasting plasma glucose) among those who were screened. Methods: We used the MarketScan Commercial Claims database (2011–2019) to identify a sample of women aged 18–64 years with PCOS who were free from diabetes at baseline and had ≥ 5 years of continuous enrollment in their insurance plan. PCOS was ascertained using International Classification of Disease diagnosis codes (ICD-9: 256.4; ICD-10: E28.2). Diabetes screening was ascertained using Current Procedural Terminology (CPT) codes (A1C: 8303683037; Fasting blood sugar: 82947; OGTT: 82950). Diabetes screening rates were calculated for the overall study sample as well as across subgroups defined by age, overweight/obesity, hypertension, hypercholesterolemia, and vascular disease. Results: In our sample of 191,110 commercially insured women with PCOS, 73.40% were screened at least once for diabetes during a five-year period. Among the women screened, 19.24% were screened using the Androgen Excess Society (AES)-recommended OGTT, 61.58% were screened using A1C, and 23.37% were screened using fasting blood sugar. Conclusions: In a sample of commercially insured individuals spanning the timeframe 2011–2019, nearly 75% of women with PCOS complied with the ACOG screening guidelines for diabetes. Although OGTT is recommended as the preferred screening tool for women with PCOS it was less commonly used than A1C and fasting blood sugar tests. [ABSTRACT FROM AUTHOR]

Background: Information on the influences of daily eating frequency (DEF) and nighttime fasting duration (NFD) on biological aging is minimal. Our study investigated the potential associations of DEF and NFD with accelerated aging. Methods: Out of 24212 participants in NHANES 2003–2010 and 2015–2018, 4 predicted age metrics [homeostatic dysregulation (HD), Klemera–Doubal method (KDM), phenoAge (PA), and allostatic load (AL)] were computed based on 12 blood chemistry parameters. Utilizing 24-h dietary recall, DEF was measured by the frequency of eating occurrences, while NFD was determined by assessing the timing of the initial and final meals throughout the day. Weighted multivariate linear regression models and restricted cubic spline (RCS) were utilized to examine the associations. Results: Compared to DEF of ≤ 3.0 times, subjects with DEF ≥ 4.6 times demonstrated lower KDM residual [β: -0.57, 95% confidence-interval (CI): (-0.97, -0.17)] and PA residual [β: -0.47, 95% CI: (-0.69, -0.25)]. In comparison to NFD between 10.1 and 12.0 h, individuals with NFD ≤ 10.0 h were at higher HD [β: 0.03, 95% CI: (0.01, 0.04)], KDM residual [β: 0.34, 95% CI: (0.05, 0.63)], and PA residual [β: 0.38, 95% CI: (0.18, 0.57)]. Likewise, those with NFD ≥ 14.1 h also had higher HD [β: 0.02, 95% CI: (0.01, 0.04)] and KDM residual [β: 0.33, 95% CI: (0.03, 0.62)]. The results were confirmed by the dose–response relationships of DEF and NFD with predicted age metrics. Lactate dehydrogenase (LDH) and globulin (Glo) were acknowledged as implicated in and mediating the relationships. Conclusions: DEF below 3.0 times and NFD less than 10.0 or more than 14.1 h were independently associated with higher predicted age metrics. [ABSTRACT FROM AUTHOR]