The genetic regulation of post-prandial glucose levels is poorly understood. Here, we characterise the genetic architecture of blood glucose variably measured within 0 and 24 h of fasting in 368,000 European ancestry participants of the UK Biobank. We found a near-linear increase in the heritability of non-fasting glucose levels over time, which plateaus to its fasting state value after 5 h post meal (h2 = 11%; standard error: 1%). The genetic correlation between different fasting times is > 0.77, suggesting that the genetic control of glucose is largely constant across fasting durations. Accounting for heritability differences between fasting times leads to a ~16% improvement in the discovery of genetic variants associated with glucose. Newly detected variants improve the prediction of fasting glucose and type 2 diabetes in independent samples. Finally, we meta-analysed summary statistics from genome-wide association studies of random and fasting glucose (N = 518,615) and identified 156 independent SNPs explaining 3% of fasting glucose variance. Altogether, our study demonstrates the utility of random glucose measures to improve the discovery of genetic variants associated with glucose homeostasis, even in fasting conditions.

To synthesize results from pertinent studies and determine if fasting and/or non-fasting triglycerides are a risk factor for ischemic stroke.

Considering the practice of preoperative fasting based on observations on the gastric emptying delay after induction and the time of this fast is closely linked to organic response to trauma, arise the question about preoperative fasting period necessary to minimize such response and support the professional with clinical and scientific evidence.

To estimate allele frequencies and the marginal and combined effects of novel fasting glucose (FG)-associated single nucleotide polymorphisms (SNPs) on FG levels and on risk of impaired FG (IFG) among non-Hispanic white, non-Hispanic black, and Mexican Americans.

Evidence suggests that fasting, during which only water is consumed, results in potentially health promoting physiological effects. However, peer-reviewed research assessing the safety of water-only fasting is lacking. To address this, we conducted a chart review to describe adverse events (AEs) that occurred during medically supervised, water-only fasting.

Homo sapiens evolved under conditions of intermittent food availability and prolonged fasting between meals. Periods of fasting are important for recovery from meal-induced oxidative and metabolic stress, and tissue repair. Constant high energy-density food availability in present-day society contributes to the pathogenesis of chronic diseases, including diabetes and its complications, with intermittent fasting (IF) and energy restriction shown to improve metabolic health. We have previously demonstrated that IF prevents the development of diabetic retinopathy in a mouse model of type 2 diabetes (db/db); however the mechanisms of fasting-induced health benefits and fasting-induced risks for individuals with diabetes remain largely unknown. Sirtuin 1 (SIRT1), a nutrient-sensing deacetylase, is downregulated in diabetes. In this study, the effect of SIRT1 stimulation by IF, fasting-mimicking cell culture conditions (FMC) or pharmacological treatment using SRT1720 was evaluated on systemic and retinal metabolism, systemic and retinal inflammation and vascular and bone marrow damage.

Fasting is defined as the abstinence from consuming food and/or beverages for different periods of time. Both traditional and modern healthcare systems recommend fasting as a therapeutic intervention for the management of several chronic, non-infectious diseases. Exercising during a fasting state increases lipolysis in adipose tissue while also stimulating peripheral fat oxidation, resulting in increased fat utilization and weight loss. A key focus of this review is to assess whether endurance training performed while fasting induces specific training adaptations, where increased fat oxidation improves long-term endurance levels. Fasting decreases body weight, lean body and fat content in both trained and untrained individuals. Several studies indicate a broader impact of fasting on metabolism, with effects on protein and glucose metabolism in sedentary and untrained subjects. However, there are conflicting data regarding the effects of fasting on glucose metabolism in highly trained athletes. The effects of fasting on physical performance indicators also remain unclear, with some reporting a decreased performance, while others found no significant effects. Differences in experimental design, severity of calorie restriction, duration, and participant characteristics could, at least in part, explain such discordant findings. Our review of the literature suggests that there is little evidence to support the notion of endurance training and fasting-mediated increases in fat oxidation, and we recommend that endurance athletes should avoid high intensity training while fasting.

Intermittent fasting (IF) is an increasingly popular approach to dietary control that focuses on the timing of eating rather than the quantity and content of caloric intake. IF practitioners typically seek to improve their weight and other health factors. Millions of practitioners have turned to purpose-built mobile apps to help them track and adhere to their fasts and monitor changes in their weight and other biometrics.

Intermittent fasting (IF) has been suggested to have neuroprotective effects through the activation of multiple signaling pathways. Rodents fasted intermittently exhibit enhanced hippocampal neurogenesis and long-term potentiation (LTP) at hippocampal synapses compared with sedentary animals fed an ad libitum (AL) diet. However, the underlying mechanisms have not been studied. In this study, we evaluated the mechanistic gap in understanding IF-induced neurogenesis.

The VGF-derived TLQP peptides (TLQPp), a new potential drug target for obesity, are expressed in stomach, pancreas, adrenal gland as well as in adipose tissues, and, when exogenously injected, regulate energy expenditure and food intake. However, it is not clear if these peptides physiologically change in these organs in response to fasting.

Many aspects of physiological functions are controlled by the hypothalamus, a brain region that connects the neuroendocrine system to whole-body metabolism. Growth hormone (GH) and the GH receptor (GHR) are expressed in hypothalamic regions known to participate in the regulation of feeding and whole-body energy homeostasis. Sirtuin 1 (SIRT1) is the most conserved mamma-lian nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that plays a key role in controlling life span and sensing nutrient availability in the hypothalamus in response to caloric restriction. However, the interaction between GHR signaling and SIRT1 in the hypothal-amus is not established. In the arcuate nucleus (ARC) of the hypothalamus, the anorexigenic proopiomelanocortin (POMC)-expressing neurons and the orexigenic agouti-related protein (AgRP)-expressing neurons are the major regulators of feeding and energy expenditure. We show that in the ARC, the majority of GHR-expressing neurons also express SIRT1 and respond to fasting by upregulating SIRT1 expression. Accordingly, hypothalamic upregulation of SIRT1 in response to fasting is blunted in animals with GHR deletion in the AgRP neurons (AgRPEYFPΔGHR). Our data thus reveal a novel interaction between GH and SIRT1 in responses to fasting.

This ambidirectional cohort study aimed to assess the performance of combining hemoglobin A1c (HbA1c) to fasting plasma glucose (FPG) for estimation of progression rate to diabetes mellitus (DM) and to explore the risk factors of DM in patients with impaired fasting glucose (IFG).

Numerous studies have measured changes in fasting blood glucose (FBG) levels in response to physical activity (PA) interventions. While studies involving clinical populations such as type 2 diabetics typically report significant reductions, most others report no change in FBG. This study investigated changes in FBG in apparently healthy adults following a PA intervention.

Intermittent circadian fasting, namely Ramadan, is a common worldwide practice. Such fasting has a positive impact on psoriasis, but no data exist on its role in psoriatic arthritis (PsA)-a disease that is clearly linked to body mass index. We enrolled 37 patients (23 females and 14 males) with a mean age 43.32 ± 7.81 and they fasted for 17 h for one month in 2016. The baseline PsA characteristics were collected and 12 (32.4%) patients had peripheral arthritis, 13 (35.1%) had axial involvement, 24 (64.9%) had enthesitis, and 13 (35.1%) had dactylitis. Three patients (8.1%) were treated with methotrexate, 28 (75.7%) with TNF-α blockers, and 6 (16.2%) with IL-17 blockers. After a month of intermittent fasting, C-reactive protein (CRP) levels decreased from 14.08 ± 4.65 to 12.16 ± 4.46 (p < 0.0001), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 2.83 ± 1.03 to 2.08 ± 0.67 (p = 0.0078), Psoriasis Area Severity Index (PASI) decreased from 7.46 ± 2.43 to 5.86 ± 2.37 (p < 0.0001), and Disease Activity index for PSoriatic Arthritis (DAPSA) decreased from 28.11 ± 4.51 to 25.76 ± 4.48 (p < 0.0001). Similarly, enthesitis improved after fasting, with Leeds Enthesitis Index (LEI) decreasing from 2.25 ± 1.11 to 1.71 ± 0.86 (p < 0.0001) and dactylitis severity score (DSS) decreasing from 9.92 ± 2.93 to 8.54 ± 2.79 (p = 0.0001). Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting. These preliminary data may support the use of chronomedicine in the context of rheumatic diseases, namely PsA. Further studies are needed to support our findings.

The level of low-density lipoprotein cholesterol (LDL-C) decreases to a certain extent after daily meals; however, the influencing factor of this phenomenon has not been fully elucidated. This study included 447 patients with coronary heart disease (CHD). Serum levels of blood lipid parameters at 0, 2, and 4 hours (h) after a daily breakfast were monitored in all subjects. The levels of total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C significantly decreased, while those of triglycerides (TG) and remnant cholesterol (RC) significantly increased from baseline to 4 h in both male and female patients (P < 0.05). Multiple linear regression analysis showed that fasting LDL-C level, the non-fasting change in RC level at 4 h and fasting TG level were significant predictors of the non-fasting change in LDL-C level at 4 h in patients with CHD, and fasting LDL-C level was the most significantly associated with the non-fasting change in LDL-C level. Patients with lower levels of fasting LDL-C had smaller non-fasting changes in LDL-C levels. When the fasting LDL-C level was <1.4 mmol/L, both absolute reduction and percent reduction in LDL-C level at 4 h were almost zero, which means that the non-fasting LDL-C level at 4 h was approximately equivalent to its fasting value (P < 0.05). This result indicated that the non-fasting changes in LDL-C levels were influenced by fasting LDL-C levels in patients with CHD. When the fasting LDL-C level was <1.4 mmol/L, the non-fasting LDL-C level could replace the fasting value to guide treatment.

Bottlenose dolphins (Tursiops truncatus) typically feed on prey that are high in lipid and protein content and nearly devoid of carbohydrate, a dietary feature shared with other marine mammals. However, unlike fasted-adapted marine mammals that predictably incorporate fasting into their life history, dolphins feed intermittently throughout the day and are not believed to be fasting-adapted. To assess whether the physiological response to fasting in the dolphin shares features with or distinguishes them from those of fasting-adapted marine mammals, the plasma metabolomes of eight bottlenose dolphins were compared between post-absorptive and 24-h fasted states. Increases in most identified free fatty acids and lipid metabolites and reductions in most amino acids and their metabolites were consistent with the upregulation of lipolysis and lipid oxidation and the downregulation of protein catabolism and synthesis. Consistent with a previously hypothesized diabetic-like fasting state, fasting was associated with elevated glucose and patterns of certain metabolites (e.g. citrate, cis-aconitate, myristoleic acid) indicative of lipid synthesis and glucose cycling to protect endogenous glucose from oxidative disposal. Pathway analysis predicted an upregulation of cytokines, decreased cell growth and increased apoptosis including apoptosis of insulin-secreting β-cells. Metabolomic conditional mutual information networks were estimated for the post-absorptive and fasted states and 'topological modules' were estimated for each using the eigenvector approach to modularity network division. A dynamic network marker indicative of a physiological shift toward a negative energy state was subsequently identified that has the potential conservation application of assessing energy state balance in at-risk wild dolphins.

The branched-chain amino acids (BCAA) leucine, valine, and isoleucine provide precursors for monomethyl branched-chain fatty acids (BCFA). Established reference ranges for BCFAs are lacking. In maple syrup urine disease (MSUD), a rare inborn error of BCAA metabolism, the endogen production is impaired and MSUD patients are treated with a low protein (low BCAA) diet. The protein restriction may affect the dietary intake of BCFA, depending on the dietary choices made. Patients with MSUD are prescribed a more or less protein-restricted diet depending on the severity of the disease. The combination of a protein-restricted diet and subsequent impaired endogenous synthesis may render MSUD patients sensitive to BCFA deficiency, with yet unknown implications. To investigate the possibility of lower circulatory BCFA levels in MSUD that favors dietary BCFA supplementation, we first established fasting-state reference ranges for selected BCFAs and saturated/unsaturated fatty acids in plasma. Then, the effect of fasting on BCFA levels was evaluated by comparing the distribution in a fasting versus a non-fasting cohort. To test the hypothesis that BCFA deficiency could contribute to MSUD pathophysiology, we recruited patients with intermittent, intermediate, and classical form of MSUD and analyzed the corresponding BCFA z-scores. None of the BCFA species had |z-scores| > 2 relative to the reference range. Our findings do not support the requirement of BCFA supplementation in MSUD patients. The origin of BCFAs is discussed. Impaired capacity to synthesize BCFA do not manifest as reduced plasma levels in MSUD, suggesting that endogenous synthesis is dispensable for plasma levels.

Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2), one of the most abundant circulating IGFBPs, is known to attenuate the biological action of IGF-1. Although the effect of IGFBP-2 in preventing metabolic disorders is well known, its regulatory mechanism remains unclear. In the present study, we demonstrated the transcriptional regulation of the Igfbp-2 gene by peroxisome-proliferator-activated receptor (PPAR) α in the liver. During fasting, both Igfbp-2 and PPARα expression levels were increased. Wy14643, a selective PPARα agonist, significantly induced Igfbp-2 gene expression in primary cultured hepatocytes. However, Igfbp-2 gene expression in Pparα null mice was not affected by fasting or Wy14643. In addition, through transient transfection and chromatin immunoprecipitation assay in fasted livers, we determined that PPARα bound to the putative PPAR-responsive element between -511 bp and -499 bp on the Igfbp-2 gene promoter, indicating that the Igfbp-2 gene transcription is activated directly by PPARα. To explore the role of PPARα in IGF-1 signalling, we treated primary cultured hepatocytes with Wy14643 and observed a decrease in the number of IGF-1 receptors (IGF-1Rs) and in Akt phosphorylation. No inhibition was observed in the hepatocytes isolated from Pparα null mice. These results suggest that PPARα controls IGF-1 signalling through the up-regulation of hepatic Igfbp-2 transcription during fasting and Wy14643 treatment.

Fasting strategies are under active clinical investigation in patients receiving chemotherapy. Prior murine studies suggest that alternate-day fasting may attenuate doxorubicin cardiotoxicity and stimulate nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis. In this study, human heart tissue from patients with doxorubicin-induced heart failure demonstrated increased nuclear TFEB protein. In mice treated with doxorubicin, alternate-day fasting or viral TFEB transduction increased mortality and impaired cardiac function. Mice randomized to alternate-day fasting plus doxorubicin exhibited increased TFEB nuclear translocation in the myocardium. When combined with doxorubicin, cardiomyocyte-specific TFEB overexpression provoked cardiac remodeling, while systemic TFEB overexpression increased growth differentiation factor 15 (GDF15) and caused heart failure and death. Cardiomyocyte TFEB knockout attenuated doxorubicin cardiotoxicity, while recombinant GDF15 was sufficient to cause cardiac atrophy. Our studies identify that both sustained alternate-day fasting and a TFEB/GDF15 pathway exacerbate doxorubicin cardiotoxicity.

Clinical data on the modern topic fasting among cancer patients are rare. This review aimed to summarise published clinical data on fasting and its effects on patients undergoing chemotherapy and therefore to give some directions in advising patients with the desire to fast.