12-h Fast Research Articles

Fasting regulates expression of voltage-gated Na+ channel Nav1.3 in subfornical organ

The subfornical organ (SFO) is a sensory circumventricular organ of the central nervous system and plays a key role in regulation of a number of homeostatic processes because of its ability to detect and respond to circulating signals and communication to homeostatic control centres. A previous study reported a change in expression of 687 transcripts in rat SFO following a 48h fast; of particular interest was the observed downregulation of the transcript encoding the Nav1.3 voltage-gated Na+ channel. Therefore, we carried out a study to examine the effects of a 48h fast on electrical properties of SFO neurons. First, we carried out an immunohistochemical analysis of rat SFO to confirm expression of Nav1.3 protein. Next, we carried out qPCR analysis of mRNA from SFO of sated rats and 48h fasted rats and confirm that a 48hr fast caused a downregulation of Nav1.3. Using patch clamp analysis of SFO neurons acutely isolated from rats following a 48h fast, a statistically significant decrease in peak Na+ current density, as well as shifts in voltage dependence of activation and inactivation, and a slowing to time dependent recovery from inactivation were observed. These changes were accompanied by a depolarization of the threshold to fire action potentials and a decrease in frequency of spontaneous action potentials. Together, these data show that the electrical properties of SFO neurons are altered by a 48hr fast, indicating SFO is a dynamic sensor of circulating signals.

Hypothyroidism modulates mitochondrial dynamics and mitophagy in the heart of rats under fed and fasting conditions

AimsInvestigate the impact of hypothyroidism on mitochondrial dynamics and mitophagy in the heart under fed and fasting conditions. MethodsHypothyroidism was induced in male Wistar rats with methimazole (0.03 %) for 21 days. Half of the euthyroid and hypothyroid groups underwent a 48-h fasting. Mitochondrial number and ultrastructure were evaluated by transmission electron microscopy. Fusion, fission, mitophagy, oxidative stress, and mitochondrial oxidative phosphorylation system (OXPHOS) components were analyzed by Western Blot and qPCR. ResultsHypothyroidism increased DRP1 activation and the p-DRP1/OPA1 ratio, indicating a shift toward mitochondrial fission over fusion. Under fasting, hypothyroidism prevented the increases in mitochondrial size, elongation, OPA1, and OXPHOS seen in euthyroid fasted rats. Hypothyroidism also raised 4-HNE content, an oxidative stress product, increased mitochondrial injury, and exacerbated fasting-related mitochondrial damage. This was accompanied by elevated Parkin levels in both fed and fasted hypothyroid groups, but without changes in PINK1 levels or Parkin activation. While fasting upregulated Bnip3l and Map1lc3b expression in euthyroid rats, hypothyroidism suppressed this response, though it did not prevent fasting-induced Bnip3 increases. ConclusionsHypothyroidism increases the activation of mitochondrial fission machinery and oxidative stress, and induces mitochondrial damage without activation of mitophagy proteins, suggesting disrupted mitophagy signaling. It also interferes with fasting-induced mitochondrial dynamics adaptations, highlighting the essential role of thyroid hormones in metabolic adaptation to fasting.

An enhanced machine learning algorithm for type 2 diabetes prognosis with a detailed examination of Key correlates

This study aimed to construct a high-performance prediction and diagnosis model for type 2 diabetic retinopathy (DR) and identify key correlates of DR. This study utilized a cross-sectional dataset of 3,000 patients from the People’s Liberation Army General Hospital in 2021. Logistic regression was used as the baseline model to compare the prediction performance of the machine learning model and the related factors. The recursive feature elimination cross-validation (RFECV) algorithm was used to select features. Four machine learning models, support vector machine (SVM), decision tree (DT), random forest (RF), and gradient boost decision tree (GBDT), were developed to predict DR. The models were optimized using grid search to determine hyperparameters, and the model with superior performance was selected. Shapley-additive explanations (SHAP) were used to analyze the important correlation factors of DR. Among the four machine learning models, the optimal model was GBDT, with predicted accuracy, precision, recall, F1-measure, and AUC values of 0.7883, 0.8299, 0.7539, 0.7901, and 0.8672, respectively. Six key correlates of DR were identified, including rapid micronutrient protein/creatinine measurement, 24-h micronutrient protein, fasting C-peptide, glycosylated hemoglobin, blood urea, and creatinine. The logistic model had 27 risk factors, with an AUC value of 0.8341. A superior prediction model was constructed that identified easily explainable key factors. The number of correlation factors was significantly lower compared to traditional statistical methods, leading to a more accurate prediction performance than the latter.

Plasma and serum volume remain unchanged following a 12-h fast from food and drink despite changes in blood and urinary hydration markers.

The effect of mild dehydration on plasma and serum volume has not been well established. Furthermore, the ability of urinary and blood biomarkers to monitor small hydration changes have not been solidified. There were two objectives of this research: 1. Determine if mild dehydration affects plasma and serum volume; 2. Determine if mild dehydration can be detected better by urinary or blood biomarkers. 47 subjects were recruited; 10 subjects were removed from the study and 37 subjects (27% male) completed the study. This was a crossover study design such that each subject underwent all protocols in a counterbalanced order. Protocols consisted of 12-h dehydration, 12-h hydration, and control. Neither plasma volume (p = 0.914), plasma volume status (p = 0.649), nor serum volume (p = 0.273) were different among protocols. Body mass (p < 0.001) was lower following the dehydration protocol. Urine color (p < 0.001), urine osmolality (p < 0.001), urine specific gravity (p < 0.001), serum osmolality (p < 0.001), and plasma osmolality (p < 0.001) were all lower following the hydration protocol. Hematocrit (p = 0.842) and hemoglobin concentration (p = 0.558) were not different among protocols. Dehydration did not affect plasma or serum volume. Therefore, a 12-h fast from food and water as done in this study will not likely affect laboratory test results of biomarker concentration. All 3 urinary measures were able to detect changes in hydration status, whereas only 2 blood measures were able to detect changes in hydration status. This may indicate that urinary measures are best at detecting small changes in hydration status.

Insight into didecyl dimethyl ammonium bromide toxicity following acute exposure in pullets (Gallus gallusdomesticus).

Didecyl dimethyl ammonium bromide (DDAB) is a quaternary ammonium compound used for the sanitation of drinking water of poultry and water pipelines in farms. There is scarcity of information on the toxicology of DDAB in poultry. This study set out to profile the acute toxicity of DDAB in poultry. Issa brown pullets (n = 34) as experimental birds were orally administered varying doses of DDAB, using a syringe, after 12h fasting, and observed for toxicity over 14 days. Control birds (n = 10) were similarly given normal saline orally. Toxic signs in the experimental birds were depression, anorexia, adipsia, vocalization with foamy salivation, later emaciation and death. The LD50 was calculated as 458.00mg/kg. Birds given 2151mg/kg DDAB died within 24h, while those treated with 516mg/kg succumbed on Day 14. At necropsy, grossly, there were necrosis and sloughing of the oesophagus and intestines, pale and friable liver, congested and necrotic lungs, friable popped out kidneys and emaciated carcasses. Microscopically, desquamation and necrosis of the oesophagus, crop, proventriculus and intestines and disruption of the koilin membrane of the gizzard were observed. The lungs, liver and kidneys were congested with mononuclear cellular infiltration plus loss of architecture in the lungs and liver. In conclusion, at high doses, DDAB caused significant toxicity in chickens and these findings provide new information which could serve as a guide in the diagnosis of quaternary ammonium toxicity in chicken. The results could be extrapolated to other quaternary ammonium toxicities in related avian species.

The impact of an oral glucose load on IFN-γ-release in persons infected with Mycobacterium tuberculosis

Background and objectiveTo diagnose tuberculosis infection (TBI), whole blood is incubated with M.tuberculosis (Mtb)-specific peptides and the release of interferon-γ (IFN-γ) is measured in IFN-γ-release assays (IGRAs). Hyperglycaemia and fluctuations in blood glucose may modulate IFN-γ-release. Here, we investigated if glucose intake affects IFN-γ-release or IGRA results in IGRAs taken during an oral glucose tolerance test (OGTT).MethodsPersons with TB disease (TB) or TBI underwent a standard 75-g OGTT at the start and end of treatment for TB or TBI. Blood for the IGRA QuantiFERON-TB Gold Plus (QFT) containing Mtb-specific tubes (TB1 and TB2), a non-specific mitogen tube (MIT) and an empty control tube (NIL) was drawn at sample-timepoints -15 (baseline), 60, 90, 120 and 240 min during the OGTT. Blood glucose was measured in parallel at all timepoints. IFN-γ-release (after subtraction of NIL) at each timepoint was compared with baseline using linear-mixed-model analysis.ResultsTwenty-four OGTTs from 14 participants were included in the final analysis. Compared to baseline, IFN-γ-release was increased at sample-timepoint 240 min for TB1; geometric mean (95% confidence interval) 3.0 (1.5–6.2) vs 2.5 (1.4–4.4) IU/mL (p = 0.047), and MIT; 182.6 (103.3–322.9) vs 146.0 (84.0–254.1) IU/mL (p = 0.002). Plasma glucose levels were not associated with IFN-γ-release and the QFT test results were unaffected by the OGTT.ConclusionIngestion of glucose after a 10-h fast was associated with increased IFN-γ-release after 240 min in the MIT tube. However, there was no association between plasma glucose levels at the QFT sampling timepoint and IFN-γ-release. Furthermore, the QFT test results were not affected by glucose intake. The overall effect of an OGTT and prevailing plasma glucose levels on IFN-γ-release in IGRAs seem limited.Trial registrationTrial registration ID: NCT04830462 (https://clinicaltrials.gov/study/NCT04830462). Registration date: 05-Apr-2021.

Obesity alters adipose tissue response to fasting and refeeding in women: A study on lipolytic and endocrine dynamics and acute insulin resistance

Fasting induces significant shifts in substrate utilization with signs of acute insulin resistance (IR), while obesity is associated with chronic IR. Nonetheless, both states substantially influence adipose tissue (AT) function. Therefore, in this interventional study (NCT04260542), we investigated if excessive adiposity in premenopausal women alters insulin sensitivity and AT metabolic and endocrine activity in response to a 60-h fast and a subsequent 48-h refeeding period. Using physiological methods, lipidomics, and AT explants, we showed that obesity partially modified AT endocrine activity and blunted the dynamics of AT insulin resistance in response to the fasting/refeeding challenge compared to that observed in lean women. AT adapted to its own excess by reducing lipolytic activity/free fatty acids (FFA) flux per mass. This adaptation persisted even after a 60-h fast, resulting in lower ketosis in women with obesity. This could be a protective mechanism that limits the lipotoxic effects of FFA; however, it may ultimately impede desirable weight loss induced by caloric restriction in women with obesity.

Rapid supervised levothyroxine absorption test in refractory hypothyroidism: suggestion for assessing absorption using two blood samples in low-resource settings.

Refractory hypothyroidism is associated with high morbidity and increased healthcare expenditure. In general, the use of the levothyroxine absorption test looks promising in evaluating refractory hypothyroidism but has shown significant variability in protocols in multiple settings. We intended to assess the usefulness of the levothyroxine absorption test in a low-resource setting and to assess the factors associated with refractory hypothyroidism. A cross-sectional study among age-matched 25 cases of refractory hypothyroidism and 24 treatment-responsive hypothyroid controls was conducted. A supervised levothyroxine absorption test was performed with levothyroxine 1000 μg tablets after a 10-h fast, and serum free tetraiodothyronine (FT4) levels were measured at 0, 1, 2, 3, 4, and 5 h. Descriptive statistics, chi-square test, Student's t-test, and logistic regression were used in the analysis. Results showed no significant difference in age, body weight, etiology of hypothyroidism, interfering medications, thyroxine storage, and ingestion technique in cases and controls. Cases had a longer duration of hypothyroidism and males had a higher peak FT4 concentration. During pooled analysis, serum FT4 peaked at 3 h with an increment of 149.4% (128.4-170.5%) from baseline and plateaued thereafter. The absolute value of FT4 at 3 h was 41.59 (s.d. 14.14) pmol/L (3.23 ng/dL). We concluded that there was no significant difference in the pattern of levothyroxine absorption in both groups. The most common cause of refractory disease was pseudo-malabsorption. Rapid supervised levothyroxine absorption test with two blood samples for FT4 at baseline and at the peak of absorption (3 h) is simple, convenient, and cost-effective, particularly in low-resource settings.

Calibration of 24-h urinary sodium excretion estimates from fasting morning urine in Chinese populations: a comparative analysis of 2 calibration models and a locally developed model

BackgroundSpot urine collection offers a convenient alternative to the more cumbersome 24-h urine collection. However, the widely recognized estimation models, such as Tanaka and International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT), have not been adequately adapted for widespread use in the general Chinese population. ObjectivesThis study was designed to evaluate the precision of the Tanaka and INTERSALT calibration models, alongside a locally Zhejiang Province-formulated model, in predicting 24-h urinary sodium (24-hUNa) excretion among the Chinese population. MethodsThe study comprised 1424 participants, aged 18–69 y, who provided both comprehensive 24-h urine and fasting morning urine samples. The researchers assessed the accuracy of the measured 24-hUNa against the estimates obtained from the Tanaka, INTERSALT, and Zhejiang models. This evaluation was conducted at both population and individual levels, employing a range of statistical techniques, including bias analysis, correlation coefficients, intraclass correlation coefficients, receiver operating characteristic curves, Bland–Altman plots, as well as relative and absolute difference calculations, and misclassification rates. ResultsThe measured average 24-hUNa excretion was found to be 165.7 ± 71.5 mmol/24-h. Notably, there was a significant deviation between the estimated and measured values for the Tanaka-adjusted model [−11.7 mmol, 95% confidence interval (CI): −16.7, −6.7 mmol/24-h], indicating a statistically significant difference. In contrast, the deviations for the INTERSALT-adjusted model (0.6 mmol, 95% CI: −4.2, 5.4 mmol/24-h) and the Zhejiang model (0.2 mmol, 95% CI: −4.6, 5.0 mmol/24-h) were nonsignificant. The correlation coefficients for the models were 0.303, 0.398, and 0.391, respectively, with the INTERSALT-adjusted and Zhejiang models showing superior performance at the population level. ConclusionsThe 3 evaluation models may serve as effective, low-burden alternatives for assessing urinary sodium levels in the population. However, to enhance the accuracy and reliability of predictions at the individual level, further repeated measurements are necessary to minimize measurement errors and augment the validity of the estimations.

Time-restricted eating affects human adipose tissue fat mobilization.

Time-restricted eating (TRE), a dietary approach that confines food intake to specific time windows, has shown metabolic benefits. However, its impact on body weight loss remains inconclusive. The objective of this study was to investigate the influence of early TRE (eTRE) and delayed TRE (dTRE) on fat mobilization using human adipose tissue (AT) cultures. Subcutaneous AT was collected from 21 participants with severe obesity. We assessed fat mobilization by measuring glycerol release in AT culture across four treatment conditions: control, eTRE, dTRE, and 24-h fasting. TRE had a significant impact on lipolysis (glycerol release [mean (SD)] in micromoles per hour per gram: control, 0.05 [0.003]; eTRE, 0.10 [0.006]; dTRE, 0.08 [0.005]; and fasting, 0.17 [0.008]; p < 0.0001). Both eTRE and dTRE increased lipolysis compared with the control group, with eTRE showing higher glycerol mobilization than dTRE during the overall 24-h time window, especially at the nighttime/habitual sleep episode (p < 0.0001). Further analysis of TRE based on fasting duration revealed that, independently of the time window, glycerol release increased with fasting duration (in micromoles per hour per gram: 8 h = 0.08 [0.001]; 12 h = 0.09 [0.008]; and 16 h of fasting = 0.12 [0.011]; p < 0.0001). This study provides insights into the potential benefits of TRE on fat mobilization and may guide the design of future dietary strategies for weight management and metabolic health.

Gut microbiome related to metabolic diseases after moderate-to-vigorous intensity exercise

Background objectivesThe purpose of this study is to investigate changes in gut microbiota related to metabolic diseases after moderate and high-intensity exercise. A total of 24 participants were divided into three groups: Non-Exercise Group (NEG, n = 8, 28.6 ± 5.3 years, 176.0 ± 7.8 cm, 81.3 ± 14.6 kg), Moderate Intensity Exercise Group (MIEG, n = 8, 26.5 ± 3.3 years, 176.9 ± 5.0 cm, 75.4 ± 9.5 kg), and Vigorous Intensity Exercise Group (VIEG, n = 8, 30.6 ± 5.9 years, 174.2 ± 3.5 cm, 77.8 ± 12.2 kg). MethodsThe participants were selected by assessing physical activity, gut health status, presence of diseases, recent disease diagnoses, and dietary disorders. Those who reported any presence disease or recent disease diagnosis were excluded from the current study. Stool samples were collected after a 10-h fast for gut microbiome analysis. MIEG participants trained at 40–59 % heart rate reserve (HRR) for at least 150 min per week, while VIEG participants trained at ≥ 60 % HRR for at least 90 min per week. After 4 weeks, all participants provided stool samples for gut microbiome analysis.Data analysis was conducted using the Wilcoxon test, with statistical significance set at ≤ 0.05. ResultsThe results indicated an increase in Prevotella in MIEG, while Veillonella, Dorea_formicigenerans, and Dorea_longicatena exhibited a decrease (p < 0.05). In VIEG, there was an increase in Bacteroides, Butyricimonas, Odoribacter, and Alistipes (p < 0.05). ConclusionThese modified microbial groups were associated with factors related to metabolic diseases, including inflammatory bowel disease, obesity, colorectal cancer, diabetes, hypertension, metabolic liver diseases, and ischemic heart diseases. Additional research is essential to delve into the relationship between exercise and these alterations in the microbiome.

Pre-housing fasting and diet physical form impact broiler chicks’ gastrointestinal development along the first week of housing

This study aimed to evaluate body and gastrointestinal development in broilers chicks subjected or not to pre-housing fasting and different diet physical forms during the first week of housing. Nine hundred chicks were distributed into a completely randomized design in a 3×3 factorial arrangement: 0, 24 and 48 hours(h) of fasting; mashed (MM), crushed (CC) and micropelletized (MP) physical forms. For each fasting period, 300 animals were housed in protection circles with 100 chicks each. On days 1, 3, 5 and 7 of feeding, six animals were randomly selected, previously weighed and euthanized to obtain organs biometrical and histological data. Chicks fasted for 24 h and 48 h were lighter compared to the 0 h group and the 24-h fasting x MP interaction had a positive impact on body weight at d7 (P<0.05). Although fasted chicks presented lower body weight, small intestine, liver and gizzard were heavier, and presented greater yolk sac consumption (YSC; P<0.05). There were no alterations in the duodenal mucosa (DM) in pre-housing fasting animals (P>0.05). Despite the diet physical form and pre-housing fasting interactions for villus height (VH) and absorptive area (AA) on d1, only diet physical form affected DM, where greater VH and AA on d7 were observed in CC and MP groups (P<0.05). Animals fed MP after 48 h fasting presented smaller VH and AA compared to chicks fed the same diet after 24 h and were similar to the 0 h group (P<0.05). On d1, YSC was similar among groups of the same diet, but for those fed with MP(P<0.05). The 48 h-fasted group presented heavier intestines relative weights (IRW) at d1(P<0.05). Furthermore, the 0 h group fed with CC presented higher IRW, whereas MP showed the lowest IRW over the first week (P<0.05). The DM development (kinetics) showed an increase in VH and AA overtime in all groups, which was more pronounced in 48 h-fasting chicks throughout the first week, showing the highest increase in VH when fed with MP (P<0.05). VH:CD ratio was similar along the first week in MP groups, regardless of the fasting period but more pronounced in the 24 h group fed MM and CC (P<0.05). Therefore, 24 h fasting associated to MP diet may be the most efficient management practice. Collectively, these findings suggest pre-housing fasting is strongly associated with diet physical form at the first week of housing and should be considered to achieve greater performance in broilers.

Dietary restriction and fasting alleviate radiation-induced intestinal injury by inhibiting cGAS/STING activation

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy, limiting the clinical application of this treatment. Evidence shows the potential benefits of dietary restriction in improving metabolic profiles and age-related diseases. The present study investigated the effects and mechanisms of dietary restriction in radiation-induced intestinal injury. The mice were randomly divided into the control group, 10 Gy total abdominal irradiation (TAI) group, and groups pretreated with 30% caloric restriction (CR) for 7 days or 24 h fasting before TAI. After radiation, the mice were returned to ad libitum. The mice were sacrificed 3.5 days after radiation, and tissue samples were collected. CR and fasting reduced radiation-induced intestinal damage and promoted intestinal recovery by restoring the shortened colon length, improving the impaired intestinal structure and permeability, and remodeling gut microbial structure. CR and fasting also significantly reduced mitochondrial damage and DNA damage, which in turn reduced activation of the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) pathway and the production of type I interferon and other chemokines in the jejunum. Since the cGAS/STING pathway is linked with innate immunity, we further showed that CR and fasting induced polarization to immunosuppressive M2 macrophage, decreased CD8+ cytotoxic T lymphocytes, and downregulated proinflammatory factors in the jejunum. Our findings indicated that CR and fasting alleviate radiation-induced intestinal damage by reducing cGAS/STING-mediated harmful immune responses.

Effects of Different Protein Sources on Amino Acid Absorption and Plasma Appearance of Tryptophan, Large Neutral Amino Acids, and Tryptophan Metabolites in Pigs

BackgroundAbsorption of tryptophan (TRP) across the gut epithelium is potentially modulated by competing large neutral amino acids (LNAAs), which could affect the appearance of TRP and its metabolites in the bloodstream. ObjectivesThis study aimed to determine, in a growing pig model of an adult human, the absorption of TRP and other LNAAs from the gastrointestinal tract, and plasma appearance of TRP, LNAAs, and TRP metabolites, in response to dietary proteins varying in TRP content. MethodsPigs were adapted for 7 d to each of 4 diets that differed in their protein source and TRP content: 1) alpha-lactalbumin (AL; 9.95 mg TRP/g diet DM), 2) whey protein (6.59 mg TRP/g), 3) casein (3.73 mg TRP/g), or 4) zein (0.14 mg TRP/g). On day 8, pigs were euthanised after a 12-h fast (baseline), or 1, 2, 3, 4, or 6 h after they received a test meal consisting of 45 g protein, or a protein-free meal (n = 6 pigs at each time in each meal group). Tryptophan and LNAA absorption from the small intestine, and appearance of TRP, LNAAs, and TRP metabolites (melatonin, serotonin, kynurenine pathway metabolites), in the portal vein and systemic circulation, were determined. ResultsAL intake resulted in sustained elevated plasma TRP concentrations after an overnight fast. The amount of TRP absorbed was dose-dependently related to protein TRP content (P = 0.028), with fastest rates for pigs fed AL (371 mg/h). Portal and systemic plasma TRP, TRP/LNAA, and the TRP metabolites were highest (P ≤ 0.05) after AL intake, and remained above baseline levels for ∼4 h postprandially. Absorption rates of TRP correlated with postprandial plasma TRP and TRP metabolites (P ≤ 0.05). ConclusionsIn adult humans, postprandial plasma TRP and TRP metabolite concentrations can likely be modulated by the TRP content of the meal.

Frequency and Severity of Hypoglycemia Under Conditions of Increased Hypoglycemic Risk with Insulin Efsitora Alfa Versus Insulin Glargine Treatment in Participants with Type 2 Diabetes.

Insulin efsitora alfa (efsitora) is a basal insulin with a flat pharmacokinetic profile and long half-life, enabling weekly dosing. These attributes may provide stable glucose levels. This exploratory phase 1 study aimed to assess the hypoglycemic risk during experimental conditions that mimic situations encountered in daily life. This was a single-site, open-label, two-period, fixed-sequence study in participants with type 2 diabetes (T2D) previously treated with basal insulin. The incidence, duration, and nadir glucose of hypoglycemia were assessed after treatment with efsitora versus insulin glargine (glargine) during three provocation conditions: 24-h prolonged fasting, prolonged fasting with exercise, and double dosing of study insulin. The 54 enrolled adults (BMI 21.8-39.7kg/m2, HbA1c 6.5-9.4%) achieved stable fasting glucose before undergoing provocation. Most hypoglycemic events were level 1 (≥ 54 to < 70mg/dL) and resolved spontaneously or after oral glucose. The incidences of level 1 hypoglycemia for efsitora and glargine were not significantly different: for prolonged fasting, the incidences were 44.7 vs. 42.6% and the difference in proportion was 2.1% (95% CI: - 17.2, 21.4); for prolonged fasting with exercise, the corresponding values were 65.9 vs. 50.0% and 15.9% (- 3.0, 34.8); for double dosing, the corresponding values were 68.1 vs. 61.7% and 6.4% (- 12.8, 25.6). Level 2 hypoglycemia (< 54mg/dL) was infrequent during both treatments and all provocations. No severe hypoglycemia was observed. Mean nadir glucose (range 62.8-66.3mg/dL) and hypoglycemia duration (range 76.6-115.2min) were also similar for the two treatments, depending on the provocation. Overall, weekly efsitora did not increase the incidence, duration, or severity of hypoglycemia compared to daily glargine during provocation periods in patients with T2D. ClinicalTrials.gov identifier NCT04957914.

Altered glucose kinetics occurs with aging: a new outlook on metabolic flexibility.

Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios [RER = carbon dioxide production (V̇co2)/oxygen consumption (V̇o2)] during a 2-h 75-g oral glucose tolerance test (OGTT). After an 12-h overnight fast, 28 participants, 15 young (21-35 yr; 7 men and 8 women) and 13 older (60-80 yr; 7 men and 6 women), received venous primed-continuous infusions of [6,6-2H]glucose and [3-13C]lactate with a [Formula: see text] bolus. After a 90-min metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 min post glucose consumption, peaked at 60 min, and remained elevated. As assessed by rates of appearance (Ra) and disposal (Rd) and metabolic clearance rate (MCR), glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population after the oral glucose challenge. Finally, there were no differences in 12-h fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population after a glucose challenge. Furthermore, those physiological deficits are not detected from changes in RER during an OGTT.NEW & NOTEWORTHY To determine metabolic flexibility in response to an OGTT, we studied healthy young and older men and women to determine glucose kinetics and changes in RER. Compared to young subjects, glucose kinetics were suppressed in older healthy individuals during an OGTT. Surprisingly, the age-related changes in glucose flux were not reflected in RER measurements; thus, RER measurements do not give a complete view of metabolic flexibility in healthy individuals.

Association of systemic inflammatory indices with anthropometric measures, metabolic factors, and liver function in non-alcoholic fatty liver disease

The present cross-sectional study aimed to explore the relationship between systemic inflammatory indices (SIIs) and anthropometric measures, metabolic, and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). This study was carried out on 238 NAFLD patients with overweight or obesity, aged 18–55 years. Anthropometric measurements were done and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were estimated. Metabolic factors including serum glucose, lipid profile, liver function biomarkers, and complete blood cell count were assessed after a 24-h fasting state. SIIs including the ratios of neutrophil to lymphocyte (NLR), monocytes to lymphocyte (MLR), platelet to lymphocyte (PLR), and monocytes to high-density lipoprotein cholesterol (MHR) were calculated. Results indicate that apart from PLR, all of the SIIs significantly changed by increasing steatosis severity (all p < 0.05). Moreover, changes in NLR showed a significant association with anthropometric indices including waist circumference (p = 0.032), BMI (p = 0.047), and WHtR (p = 0.002), as well as levels of fasting blood sugar (p = 0.045), triglycerides, (p = 0.025) and low-density lipoprotein cholesterol (p = 0.006). The findings also indicate the relations between lipid profile and all studied SIIs, notably MHR and MLR. All of the SIIs exhibited associations with some liver function indices as well. MHR was positively correlated with the metabolic risk factors of NAFLD while, oppositely, PLR was considered as a preventive marker of NAFLD.

Exploring the therapeutic potential of plasma from intermittent fasting and untreated rats on aging-induced liver damage.

This research aims to investigate the effects of plasma from 12-month-old intermittently fasting rats (IFpls) and untreated rats (Npls) on the liver biomolecules and histological changes in 24-month-old male Sprague-Dawley rats. Fasting rats underwent an 18-h daily fasting period and a 6-h feeding window for 35 days. The plasma was administered bi-daily, and blood samples were examined for specific liver biomolecules. Fourier transform infrared (FTIR) spectroscopy and linear discriminant analysis (LDA) was used to identify molecular profiles. Liver sections were stained for histopathological evaluation, and the expression levels of Notch signalling pathway components were assessed. Distinct molecular profiles were identified across liver biomolecules, lipids, proteins and nucleic acids with high accuracy. Notably, IFpls was found to protect against hepatic instability, microvesicular steatosis and liver fibrosis by decreasing lymphatic infiltration density and Notch pathway expression levels. Both treatments reduced protein oxidation and carbonylation, with Npls showing a pronounced decrease in protein oxidation. Furthermore, Npls increased protein conformation and glycogen/phosphate content, while IFpls increased glucose/protein content. Both IFpls and Npls induce substantial and unique alterations in liver biomolecules. IFpls offers a protective effect on various liver conditions, while Npls exhibits promising results in reducing protein oxidation and altering biomolecule content. These findings offer valuable insights for future research and potential therapeutic approaches.

Safe Continuation of Glucagon-like Peptide 1 Receptor Agonists at Endoscopy: A Case Series of 57 Adults Undergoing Endoscopic Sleeve Gastroplasty.

Glucagon-like receptor agonists (GLP1-RAs) have raised peri-procedural concerns due to their potential to delay gastric emptying. The American Association of Anesthesiologists has advised pausing a single dose before elective endoscopy. However, a subsequent directive from multiple gastroenterology societies underscored the need for further assessment to substantiate this practice. We aimed to evaluate the frequency of serious adverse events and retained gastric products during endoscopic sleeve gastroplasty (ESG) with uninterrupted GLP1-RA use. We conducted a retrospective evaluation of all patients undergoing ESG while on GLP1-RAs at three centers from August 2022 to February 2024. Per standard protocol, all patients had refrained from solid foods for at least 24h and maintained nil per os for 12h preceding their ESG. Records were reviewed for patient characteristics and medication type and doses. Primary outcomes included serious adverse events and retained gastric products based on patient records, procedure reports, and procedural videos. Fifty-seven consecutive adults (89.5% women, mean age of 44 ± 9years, mean BMI of 40.1 ± 8.1kg/m2, 35.1% with T2DM, and 26.3% with pre-T2DM) underwent ESG without stopping GLP1-RAs, which included semaglutide (45.6%), liraglutide (19.3%), dulaglutide (22.8%), and tirzepatide (12.3%). During intubation, endoscopy, and recovery, there were no instances of retained gastric solids, pulmonary aspiration, gastroesophageal regurgitation, or hypoxia. A ≥ 24-h pre-endoscopy liquid-only diet with ≥ 12-h pre-endoscopy fast may negate the need for GLP1-RA interruption for routine upper endoscopy in adults with native gastric anatomy.

298 Impact of ruminal acidosis on cattle energy metabolism

Abstract The objective of this study was to determine the impact of a bout of ruminal acidosis on energy metabolism of cattle unadapted to a high concentrate diet. Eleven ruminally cannulated steers [body weight (BW) = 352 kg ± 27] were blocked into 3 groups based on initial BW. Before the start of the experiment, animals were consuming a forage-based diet as well as adapted to the headbox style respiration chambers. Additionally, before the experiment, gas emission data were collected over a 24-h period when cattle received an ad libitum forage-based diet for use as a covariate in the statistical analysis. For the experiment, steers were moved into headboxes at the conclusion of a 24-h fast and subsequently received 1 of 2 treatment diets: control (CON), forage-based diet or acidosis (AC), concentrate-based diet. Steers remained in the headboxes for 48 h. Gas concentrations from each headbox were collected hourly and analyzed with an infrared photoacoustic gas analyzer. Ruminal pH, fecal pH, volatile fatty acids, and lactate were also measured during the acidosis challenge. Data were analyzed with the MIXED procedure of SAS 9.4. A treatment × day effect (P = 0.03) was observed for dry matter intake with intake being similar for both CON and AC steers on d 1 but AC steers consuming 2.02 kg less on d 2. Treatment affected ruminal pH (P &amp;lt; 0.01) as CON steers had a greater ruminal pH than AC steers. Greater total volatile fatty acids (P &amp;lt; 0.01) were observed for steers on AC treatment compared with CON. A treatment × time interaction (P &amp;lt; 0.01) was observed for ruminal lactate concentration with AC steers having greater concentrations from h 16 to 36. Fecal pH was affected by a treatment × time interaction (P = 0.05) as AC steers had lower fecal pH from h 24 to h 32. Over the 48-h observation period, there was a treatment × time interaction (P = 0.04) for carbon dioxide production as AC steers produced less CO2 after h 24. No treatment × time interaction was detected for oxygen consumption. However, there was a time effect (P &amp;lt; 0.01). Respiratory quotient was not affected by treatment, day, or their interaction (P ≥ 0.19). Heat production tended (P = 0.06) to be different between treatments, with AC having less heat production than CON. Thus, the effects of ruminal acidosis on gas emissions and energetics may be more transient during the time course of an acidotic bout or have a longer duration even after ruminal pH has recovered.